Aging and Cognitive Health Evaluation in Elders (ACHIEVE) Randomized Trial
Phase: NA
Conditions: Aging, Cognitive Decline
Sponsor: Johns Hopkins Bloomberg School of Public Health

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
1 
Aging and Cognitive Health Evaluation in Elders 
(ACHIEVE) Randomized Trial  
 
Protocol 
 
ClinicalTrials.gov Number: NCT03243422 
Co-Principal Investigators:   
 
Frank R. Lin, MD PhD 
Josef Coresh, MD PhD 
Johns Hopkins University 
 
 
Supported by: 
 
The National Institute on Aging 
Grant # R01AG055426   
 
 
V.1.11 March 23, 2023 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
2 
Changes from protocol version 1.10 to 1.11 
This final protocol update reflects clarifications and modifications necessitated by COVID, as 
well as updates to match with the final Statistical Analysis Plan. These protocol updates were 
made prior to the final database lock or unblinding. 
Minor changes (e.g., typographical and grammatical corrections, page numbering, section 
numbering and cross-references, formatting, and minor wording changes to improve clarity and 
readability) were made throughout the document. Substantive modifications are described here 
(full history of prior protocol amendments can be found in section 20): 
Affected 
section(s) 
Brief description of change 
Brief rationale for change 
Study Summary 
 
2.1 Hearing loss 
and cognition 
 
3 Overview of the 
ACHIEVE trial 
design 
 
9.2 Successful 
Aging intervention 
Expanded the name of the successful 
aging intervention to the successful aging 
health education control intervention. 
The full name is the preferred name and 
is more informative about the type of 
intervention. 
Study Summary 
Updated Outcomes and Statistical 
Methodology sections 
Updates reflect the May 9, 2022 
ACHIEVE Statistical Analysis Plan. 
1 Study objectives 
 
7.5 Other pre-
specified outcomes 
 
7.7 – Table 3. 
Schedule of 
Evaluations 
 
19.1 – Table 4. 
Schedule of 
Evaluations for 
Remote Data 
Collection 
Updated to reflect that physical and 
social functioning, health-related quality 
of life, and physical activity are other pre-
specified outcomes, not secondary 
outcomes. 
Initially at study outset, we used the term 
“secondary outcomes” to refer to all 
outcomes other than the primary 
outcome of global cognitive change, but 
in finalizing the SAP, we distinguished 
between cognitive secondary outcomes 
and the other non-cognitive pre-specified 
outcomes. The protocol is now updated 
accordingly to ensure consistency with 
the final SAP (and the ClinicalTrials.gov 
record). 
7 Data collection 
and measurements 
Expanded the descriptions of several of 
instruments/measures. 
These changes were made to provide 
more details on the instruments and how 
the outcomes are scored. 
7.4.1 Demographics 
questionnaire 
Clarified that the ACHIEVE 
demographics questionnaire is only 
completed by de novo participants. 
The schedule of evaluations had 
previously footnoted that ARIC 
participants did not need to complete the 
demographics questionnaire. 
7.5.4 RAND 36-
Item Health Survey 
 
7.6 Communication 
partners 
assessments 
 
Corrected the protocol to reflect that the 
RAND 36-Item Health Survey was 
administered instead of the SF-36. 
The freely available RAND version of the 
36-item health survey was administered 
in ACHIEVE, rather than the proprietary 
SF-36. The items are the same between 
the two measures, but the scoring differs 
slightly. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
3 
7.7 – Table 3 
Schedule of 
Evaluations 
7.7 – Table 3. 
Schedule of 
Evaluations 
Added footnote that the blood draw for 
ApoE could be done during a follow-up 
visit. 
In some instances, the blood draw was 
not able to be obtained at the baseline 
visit. As ApoE genotype is not time 
varying, the sample could be obtained at 
any study visit. 
7.7 – Table 3. 
Schedule of 
Evaluations 
Updated the footnotes previously noted 
as “Procedures that are intermittent 
based on protocol.” 
The old footnote has been split into 
several different footnotes that provide 
details about when or why the 
procedures are or are not completed, 
consistent with what was in the manuals 
of procedures for the study. 
12 Statistical 
Considerations 
 
Updated all sections to reflect what is in 
the May 9, 2022 Statistical Analysis Plan.  
The COVID-19 global pandemic led to 
suspension of in-person research study 
visits from March 2020 to June 2021 in 
order to protect participants, staff, and 
the larger community from risk of 
infection from COVID-19, which 
necessitated implementing remote data 
collection procedures. During this period, 
participants completed the neurocognitive 
battery over the phone.  Beginning in 
June 2021, in-person visits resumed, and 
some participants had delayed in-person 
Year 3 visits. The analytic approach was 
updated to reflect these changes in the 
availability and timing of neurocognitive 
data collection that were necessitated by 
the pandemic. 
12.4 Assumptions 
analysis 
 
Updated to detail the interim analysis of 
select parameters (rate of hearing 
intervention drop-in and drop-out, rate of 
attrition) used to estimate the original trial 
sample size. This interim analysis was 
conducted in June 2019 before closure of 
trial recruitment. 
Changes made based on DSMB 
recommendations 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
4 
Contents 
Study Summary ......................................................................................................................... 7 
1 
Study objectives ...........................................................................................................10 
2 
Background and rationale ............................................................................................10 
2.1 
Hearing loss and cognition ...........................................................................................10 
2.2 
Pilot research ...............................................................................................................11 
3 
Overview of the ACHIEVE trial design .........................................................................12 
4 
Study population and eligibility .....................................................................................13 
4.1 
Inclusion criteria ...........................................................................................................13 
4.2 
Exclusion Criteria .........................................................................................................14 
5 
Recruitment and retention ............................................................................................15 
5.1 
Integration within ARIC-NCS ........................................................................................15 
5.2 
Field centers ................................................................................................................16 
5.3 
Recruitment strategies .................................................................................................18 
5.4 
Retention strategies .....................................................................................................18 
6 
Participant rights and confidentiality .............................................................................19 
6.1 
Informed consent .........................................................................................................19 
6.2 
Participant confidentiality .............................................................................................20 
7 
Data collection and measurements ..............................................................................21 
7.1 
Audiometric assessment ..............................................................................................21 
7.1.1 
Case history ......................................................................................................... 21 
7.1.2 
Air conduction audiometry ................................................................................... 21 
7.1.3 
Tympanometry ..................................................................................................... 21 
7.1.4 
Bone conduction audiometry ............................................................................... 21 
7.1.5 
Word Recognition in Quiet ................................................................................... 21 
7.1.6 
Quick Speech in Noise (unaided) ......................................................................... 22 
7.2 
Cognitive battery ..........................................................................................................22 
7.2.1 
Administration ...................................................................................................... 22 
7.2.2 
Ensuring speech understanding test .................................................................... 22 
7.2.3 
Cognitive domains ............................................................................................... 23 
7.2.4 
Delayed word recall test (DWRT) ......................................................................... 23 
7.2.5 
Digit Symbol Substitution test (DSST) .................................................................. 23 
7.2.6 
Incidental learning................................................................................................ 23 
7.2.7 
Trail Making Test Part A (TMT A) ........................................................................ 24 
7.2.8 
Trail Making Test Part B (TMT B) ........................................................................ 24 
7.2.9 
Logical Memory I and II ....................................................................................... 24 
7.2.10 
Digit Span Backwards .......................................................................................... 24 
7.2.11 
Boston Naming test ............................................................................................. 25 
7.2.12 
Word Fluency ...................................................................................................... 25 
7.2.13 
Animal Naming .................................................................................................... 25 
7.3 
Dementia and MCI assessments .................................................................................25 
7.3.1 
Neurological interviews ........................................................................................ 26 
7.3.2 
Clinical Dementia Rating Scale (CDR) ................................................................. 27 
7.3.3 
Functional Assessment Questionnaire (FAQ) ...................................................... 27 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
5 
7.3.4 
Neuropsychiatric Inventory (NPI) ......................................................................... 27 
7.3.5 
Characterization of participants who leave the study early ................................... 27 
7.4 
Inclusion/exclusion/covariates ......................................................................................28 
7.4.1 
Demographics questionnaire ............................................................................... 28 
7.4.2 
Health history questionnaire ................................................................................ 28 
7.4.3 
Neurologic History ............................................................................................... 28 
7.4.4 
Anthropometry ..................................................................................................... 28 
7.4.5 
Seated blood pressure ......................................................................................... 29 
7.4.6 
Blood draw .......................................................................................................... 29 
7.4.7 
Wide Range Achievement Test (WRAT) .............................................................. 29 
7.4.8 
Pure-tone audiometry (screening) ........................................................................ 29 
7.4.9 
Vision screening .................................................................................................. 29 
7.4.10 
Mini-Mental State Exam (MMSE) ......................................................................... 29 
7.4.11 
Activities of Daily Living (ADL) ............................................................................. 30 
7.4.12 
COVID impact questionnaire ............................................................................... 30 
7.5 
Other pre-specified outcomes ......................................................................................30 
7.5.1 
Center for Epidemiological Studies Depression and Hopelessness Scale (CES-D)
 
30 
7.5.2 
Baecke Physical Activity Questionnaire ............................................................... 31 
7.5.3 
Hearing Handicap Inventory for the Elderly – Screening Version ......................... 31 
7.5.4 
RAND 36-Item Health Survey .............................................................................. 31 
7.5.5 
Social Network Index ........................................................................................... 31 
7.5.6 
UCLA Loneliness Scale ....................................................................................... 32 
7.5.7 
Accelerometry ...................................................................................................... 32 
7.5.8 
Falls and mobility ................................................................................................. 32 
7.5.9 
Hospitalizations ................................................................................................... 32 
7.5.10 
Grip strength ........................................................................................................ 32 
7.5.11 
Short Physical Performance Battery (SPPB) ........................................................ 33 
7.5.12 
Intervention Feedback Form ................................................................................ 33 
7.6 
Communication partners assessments ........................................................................33 
7.7 
Schedule of evaluations ...............................................................................................33 
8 
Randomization .............................................................................................................37 
9 
Interventions ................................................................................................................37 
9.1 
Hearing intervention .....................................................................................................37 
9.2 
Successful Aging intervention ......................................................................................39 
10 
Strategies to promote intervention adherence/compliance & minimize bias from 
unblinded study participants and staff .......................................................................................41 
11 
Safety monitoring .........................................................................................................44 
11.1 
Data and safety monitoring board ...............................................................................44 
11.2 
Adverse events ...........................................................................................................44 
12 
Statistical considerations .............................................................................................47 
12.1 
Sample size ................................................................................................................47 
12.2 
Analytic approach .......................................................................................................48 
12.3 
Global cognitive function factor score..........................................................................53 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
6 
12.4 
Assumptions analysis .................................................................................................53 
13 
Data management .......................................................................................................54 
14 
Data handling and record keeping ...............................................................................54 
15 
Quality assurance and quality control ..........................................................................55 
15.1 
Fidelity of hearing intervention ....................................................................................55 
15.2 
Fidelity of successful aging intervention ......................................................................56 
15.3 
Quality assurance of data entry...................................................................................56 
16 
Study monitoring, auditing, and inspecting ...................................................................57 
17 
Timeline .......................................................................................................................58 
18 
Organization of the study .............................................................................................59 
18.1 
Key roles of committees ..............................................................................................59 
19 
Changes as a result of COVID-19 ................................................................................60 
19.1 
Remote visits ..............................................................................................................60 
19.2 
Modifications to neurocognitive assessment ...............................................................62 
19.2.1 
Neurocognitive tests with no substantive changes ............................................... 62 
19.2.2 
CERAD recall ...................................................................................................... 62 
19.2.3 
Shortened Mini-Mental State Exam ..................................................................... 62 
19.2.4 
Oral Trails A ......................................................................................................... 62 
19.2.5 
Oral Trails B ......................................................................................................... 62 
19.3 
Addition of interim check-in calls .................................................................................62 
20 
History of protocol amendments ..................................................................................63 
21 
References ..................................................................................................................67 
22 
Appendix A:  Delivery of the Other Intervention after Completing ACHIEVE Trial ........71 
22.1 
Successful Aging intervention for participants originally randomized to the hearing 
intervention group ..................................................................................................................71 
22.1.1 
Overview ............................................................................................................. 71 
22.1.2 
Schedule of activities ........................................................................................... 71 
22.2 
Hearing intervention for participants originally randomized to the Successful Aging 
intervention group ..................................................................................................................71 
22.2.1 
Overview ............................................................................................................. 71 
22.2.2 
Blended telehealth hearing health care delivery model ........................................ 71 
22.2.3 
Schedule of activities for delivery of the hearing intervention to SA participants 
after completing ACHIEVE ........................................................................................... 72 
22.2.4 
Procedures .......................................................................................................... 72 
23 
Appendix B:  Extended Follow-Up of Successful Aging Participants after Delivery of the 
Hearing Intervention ..................................................................................................................74 
23.1 
Background and rationale ...........................................................................................74 
23.2 
Participants .................................................................................................................74 
23.3 
Schedule of activities ..................................................................................................75 
23.4 
Procedures .................................................................................................................75 
23.5 
Safety .........................................................................................................................76 
 
 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
7 
Study Summary  
Title 
Aging and Cognitive Health Evaluation in Elders (ACHIEVE) 
Randomized Trial 
Short Title 
ACHIEVE 
Field Site(s) 
• 
George W. Comstock Center, Johns Hopkins Bloomberg School of 
Public Health, Washington County, MD  
• 
University of Mississippi Medical Center, Jackson, MS  
• 
University of Minnesota, Minneapolis, MN 
• 
Wake Forest University, Forsyth County, NC 
Other Study Sites 
• 
University of South Florida (hearing intervention unit) 
• 
University of Pittsburgh (successful aging health education 
intervention unit) 
• 
Johns Hopkins University (study governance and analysis unit) 
• 
University of North Carolina, Chapel Hill, NC (Data Coordinating 
Center) 
Design 
Randomized, open-label trial comparing hearing rehabilitative 
intervention versus successful aging control intervention for rate of 
cognitive decline. 
Sample Size and 
Population 
The trial was designed to enroll approximately 850 participants, 
including participants from the ongoing Atherosclerosis Risk in 
Communities Neurocognitive Study (ARIC-NCS) and non-ARIC 
participants recruited from the community (“de novo”). Following the 
June 2019 interim analysis review, the Data and Safety Monitoring 
Board (DSMB) supported extending recruitment, and ACHIEVE 
received an administrative supplement from the National Institute on 
Aging (NIA) to extend recruitment and increase the sample size up to 
potentially 1,000 participants; 977participants were enrolled. 
Objectives 
To determine the effect of a best practice hearing rehabilitative 
intervention versus a successful aging health education control 
intervention on decline in global cognitive function (primary outcome 
measure), decline in cognitive domains, adjudicated incident dementia 
and mild cognitive impairment (MCI), physical and social functioning, 
health-related quality of life (HRQL), and physical activity in 70‐84 year‐
old well‐functioning and cognitively-normal adults with hearing loss. 
To investigate whether hearing rehabilitative intervention alters 
established trajectories of cognitive decline in participants recruited 
from ARIC-NCS, and to investigate the effect of hearing rehabilitative 
intervention on cognitive decline in persons with Alzheimer’s disease 
risk factors and biomarkers. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
8 
Main 
Inclusion/Exclusion 
Criteria 
Community-dwelling adults aged 70-84 years with mild to moderate 
audiometric hearing loss, and free from substantial cognitive impairment 
at baseline. 
Randomization and 
stratification 
1:1 permuted block randomization, stratified by severity of hearing loss 
(mild, moderate), ARIC status (ARIC or non-ARIC participant), and field 
center. Qualifying spouse/partner pairs are randomized as a unit, 
stratified by ARIC status and field center.  
Study Interventions 
Hearing intervention (HI): Participants in the hearing intervention 
group are fitted with a hearing aid, instructed to be worn on a daily 
basis for study duration, and attend four 1-hour intervention sessions 
spaced over the 2-3 months post-randomization. Re-instruction in use 
of devices and hearing rehabilitative strategies will be provided every 6 
months. 
Successful aging health education control intervention (SA): The 
Successful Aging intervention consists of four 1-hour intervention 
sessions spaced over the 2-3 months post-randomization focusing on 
participant-selected topics from the 10 Keys™ to Healthy Aging 
program and upper body stretching. Additional sessions will be 
provided every 6 months. 
Participant 
Duration 
Approximately three years, with four intervention visits in the 2-3 
months following baseline and follow-up visits every 6 months until the 
3-year visit. 
Outcomes 
Primary: Cognitive decline, as measured by the change from baseline 
in the global cognitive function factor score. 
Secondary: Time until a composite outcome of (1) adjudicated 
dementia or adjudicated MCI diagnosis, (2) a 3-point drop in the 30-
item MMSE administered in-person, or (3) a 3-point drop in a factor 
score derived from the 10-item MMSE orientation subscale and 11-item 
Blessed scale administered over the phone and rescaled to be 
equivalent to the 30-item MMSE; also, decline in the cognitive domain 
factor scores for memory, executive function, and language derived 
from in-person assessments. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
9 
Statistical 
Methodology 
Primary: Groups will be compared for the primary outcome using mixed 
effects models that account for the correlation among repeated 
measures as well as the correlation between spouses or cohabitating 
partners. If a linear trend appears reasonable, we will fit a model with a 
linear slope. If a nonlinear trend is observed, the model will be adapted 
to include time splines. Continuous time in years from the baseline will 
be the time scale. An interaction term between treatment assignment 
and time will be used to test if cognitive change differs by treatment 
assignment. Model fit will be assessed with residual plots and other 
statistics (Akaike Information Criterion, Bayesian Information Criterion, 
etc.). The primary analysis may include adjustments for baseline 
hearing loss, ARIC vs de novo status, field center, age, sex, education, 
and APOE ε4 alleles.  
Missing cognitive factor scores among ACHIEVE participants will be 
generated utilizing multiple imputation by chained equations. 
An independent DSMB will review safety outcomes on a regular basis.  
A formal interim analysis to evaluate for sample-size re-estimation was 
initially planned for when 66% of subjects completed the study. The 
formal interim analysis was cancelled at the recommendation of the 
DSMB and replaced with a sample size assumptions evaluation 
conducted in June 2019 prior to recruitment close to re-evaluate the 
parameter assumptions used to estimate the initial sample size. 
 
 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
10 
1 
Study objectives 
The aims of the Aging and Cognition Health Evaluation in Elders Randomized Trial (ACHIEVE) 
are: 
 
Primary aims 
 
Aim 1 To determine the effect of hearing rehabilitative intervention versus a successful aging 
control intervention on decline in global cognitive function (primary outcome measure) in 70‐84 
year‐old well-functioning and cognitively-normal older adults with hearing loss. 
Aim 2 To determine the effects of hearing rehabilitative intervention versus a successful aging 
control intervention on secondary outcome measures of decline in cognitive domains (memory, 
executive function, and language); composite outcome consisting of adjudicated incident 
dementia, adjudicated MCI or a 3-point decline in the MMSE; and on other pre-specified 
outcomes related to physical and social functioning, HRQL, and physical activity. 
 
Secondary Aims 
1. To investigate whether hearing rehabilitative intervention alters established trajectories 
of cognitive decline in participants recruited from ARIC-NCS. We will leverage cognitive 
data gathered over the previous 30 years in ARIC to model prior cognitive change as 
well as prospective change after enrollment in ACHIEVE. 
 
2. To investigate the effect of hearing rehabilitative intervention on cognitive decline in 
persons with Alzheimer’s disease risk factors (ApoE ε4 allele) and biomarkers 
(neurodegeneration based on structural brain MRI; brain amyloid based on PET). 
Hearing loss may act as an additional “hit” on the brain in addition to AD and vascular 
processes. However, unlike these other processes, the effects of hearing loss may still 
be modifiable with hearing interventions in late life. 
 
2 
Background and rationale 
2.1 
Hearing loss and cognition 
Novel approaches for reducing cognitive decline in older adults are needed given the aging of 
the population and the personal, socioeconomic, and public health implications of cognitive 
impairment and dementia in older adults. Epidemiologic data now strongly suggest that age-
related peripheral hearing loss in older adults is independently associated with accelerated 
cognitive decline and incident dementia. Mechanistic pathways that could underlie this observed 
association include the effects of poor audition and distorted peripheral encoding of sound on 
cognitive load, brain structure, and/or reduced social engagement. These pathways may be 
amenable to comprehensive hearing rehabilitative treatment consisting of the use of hearing 
assistive technologies (hearing aids, other integrated hearing assistive devices) and 
rehabilitative training. To date, however, there has never been a randomized trial that has 
investigated whether hearing loss treatment could reduce cognitive and other functional 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
11 
declines in older adults. The ACHIEVE study will be a randomized controlled trial nested within 
the Atherosclerosis Risk in Communities (ARIC) study. The initial target enrollment was 850 70-
84 year-old cognitively normal older adults with hearing loss, who will be randomized 1:1 to the 
hearing intervention (hearing needs assessment, fitting of hearing devices, 
education/counseling) or successful aging health education control intervention (individual 
sessions with a health educator covering healthy aging topics) 
 
2.2 
Pilot research 
We conducted a pilot study (ACHIEVE-P) from 2015-16 at the Washington County, MD ARIC 
field site. The objectives of ACHIEVE-P were to determine feasibility of study recruitment, 
randomization, and retention, assess compliance with study interventions, refine study 
protocols, and observe for an efficacy signal of the hearing intervention on early 6-month 
outcomes that may mediate downstream effects of hearing intervention on cognitive functioning. 
Participants (N=40) were randomized to either the hearing intervention or successful aging 
intervention in a 1:1 allocation ratio. Among the 40 randomized participants, 27 were from ARIC 
and 13 were recruited de novo from the community. Participants were followed until study 
completion (6 months), excluding one participant who died during follow-up for reasons 
unrelated to the study intervention.  
The hearing intervention demonstrated a clear efficacy signal for early proximal outcomes of 
communication and social functioning. Estimated changes in standardized (z-score) outcomes 
were qualitatively different by intervention assignment for all measures, including perceived 
handicap due to hearing loss (as measured by the Hearing Handicap Inventory for the Elderly, 
p<0.0001), loneliness (as measured by the UCLA Loneliness Scale), number of contacts 
(p=0.007), and diversity of social network (as measured by the Cohen Social Network Index) 
and social, mental, and physical function (as measured by the Short Form (SF)-12). For all 
measures, estimates of change since baseline are suggestive of improvement or no change for 
the hearing intervention group, as compared to poorer function in the successful aging group 
(Table 1).  
Table 1. 6-month change in standardized proximal outcomes. 
 
 
 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
12 
Cognitive performance by intervention assignment 
Estimated changes in standardized (z-score) cognitive domain scores over 6 months of follow-
up were suggestive of improvement or no change for all participants (Table 2). The greatest 
estimated improvement in cognition was for participants who received the hearing intervention 
in the domain of memory. The mean change in memory for participants randomized to the 
hearing intervention was 0.48 ± 0.69 SD, as compared to 0.19 ± 0.66 SD for participants 
randomized to the successful aging intervention. 
 
Table 2. 6-month change in standardized cognitive domain score, n =40 
 
 
3 
Overview of the ACHIEVE trial design 
The study is a randomized controlled trial. Approximately 850 participants will be randomly 
assigned to one of two groups and followed for three years: hearing intervention with hearing 
aids or successful aging health education control intervention. Participants will be community-
dwelling adults aged 70-84 years with audiometric hearing impairment defined as a four-
frequency (0.5, 1, 2, 4 kHz) pure-tone average threshold in the better-hearing ear of ≥30 
decibels (dB) and <70dB.  
The ACHIEVE clinical trial will be nested within the infrastructure of the ongoing Atherosclerosis 
Risk in Communities Neurocognitive Study (ARIC-NCS) which provides an existing, well-
characterized cohort of African-American and white participants who have been followed for 
nearly 30 years. Recruitment will be based at the four established ARIC field sites (Washington 
County, MD; Jackson, MS; Forsyth County, NC; Minneapolis Suburbs, MN). To fulfill the 
ACHIEVE sample size, non-ARIC “de novo” participants recruited from the communities 
surrounding the ARIC fields centers will also be concurrently enrolled. The recruitment ratio goal 
is 50% ARIC participants within each field center. 
The hearing intervention consists of fitting with hearing aids and other hearing assistive 
technologies supplied by a single hearing technology manufacturer (Phonak) plus four 1-hour 
comprehensive, individualized hearing rehabilitation sessions spaced over the 2-3 months post-
randomization designed to provide all of the active components of the intervention. Hearing aids 
are instructed to be worn on a daily basis for study duration. Audiologic outcomes (e.g., hearing 
aid data logging, real ear measures, speech in noise, etc.) to verify the best-practices hearing 
intervention are gathered during study intervention visits and semi-annually beginning at 6 
months post-randomization. Participants are encouraged to specify an optional Communication 
Partner (CP) who is encouraged to attend the hearing intervention sessions. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
13 
The Successful Aging intervention will follow the protocol and materials developed for the 10 
Keys™ to Healthy Aging program by the Center for Aging and Population Health Prevention 
Research Center at the University of Pittsburgh.1 This interactive, dynamic program informs 
older adults about risk factors for diseases. Participants will meet individually with a health 
educator certified to administer the program every 2-3 weeks for a total of 4 visits over 2-3 
months, and the session content will focus on a “Key”. Each session will also include a 5-10 
minute active upper body extremity stretching program as used in the Lifestyle Interventions and 
Independence for Elders (LIFE) study.2 Participants are encouraged to bring a friend or family 
member with them to intervention visits (analogous to the communication partner for 
participants randomized to the hearing intervention). Participants will return for booster sessions 
semi-annually. 
Participants will be followed for at least 3 years after randomization with annual assessments, 
and this study is designed to detect a 0.26 SD difference in rate of decline on domain-specific 
composite scores between the hearing intervention and control groups over 3 years of post-
randomization follow-up with 90% power. 
At the completion of the study, participants in the successful aging intervention may also choose 
to be fitted for a study-supplied hearing aid and provided hearing rehabilitation resource 
materials over 2-3 intervention sessions if they are interested. Participants in the hearing 
rehabilitative may also choose to meet with a health educator to cover topics in the 10 Keys™ to 
Healthy Aging program over 2-3 intervention sessions.  
 
4 
Study population and eligibility 
The study population consists of adults aged 70-84 years free from substantial cognitive 
impairment at baseline. All eligible participants must have an adult-onset audiometric hearing 
loss as measured by a pure-tone average across 4 frequencies (0.5, 1, 2, 4 kHz) ≥ 30 dB HL in 
the better-hearing ear. Participants with hearing loss that is unlikely to benefit from amplification 
(e.g., poor word recognition in quiet) will be excluded from the study. Eligibility will be 
determined over a telephone screening and an in-person screening visit or based on 
audiometric and other data collected during ARIC-NCS study visits for existing ARIC-NCS 
participants. Confirmatory audiometric testing will be conducted at the baseline visit (performed 
on the same day or a separate day from the screening visit) by the study audiologist. 
Participants who initially qualify for the study based on screening (telephone screening, in-
person screening, or screening based on ARIC-NCS data) but who do not meet study eligibility 
criteria based on data gathered at the baseline visit will be excluded from the study. Eligibility 
criteria are as follows: 
4.1 
Inclusion criteria 
To be eligible for the study, participants must meet all of the following criteria: 
• 
Age 70-84 years. Individuals aged 70-84 at the time of randomization are eligible for 
participation. This age range will allow recruitment of participants who are at risk for 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
14 
cognitive decline but who may also be expected to survive for the duration of the trial. 
This age range is estimated to allow for potential participation of 61% of participants 
currently enrolled in the ARIC study. 
• 
Community-dwelling.   
• 
Fluent English-speaker.   
• 
Residency. Participants must plan to reside in the local area for the study duration. 
• 
Audiometric hearing impairment. Participants must have adult-onset hearing 
impairment with a four-frequency pure-tone average (0.5, 1, 2, 4 kHz) in the better-
hearing ear of ≥30 dB HL (decibels hearing level) and <70 dB HL. This level of hearing 
impairment is the level at which individuals would be most likely to benefit from the use 
of conventional amplification devices such as hearing aids. 
• 
Word Recognition in Quiet score ≥60% in better ear. A word recognition in quiet 
score <60% suggests hearing impairment that is too severe to benefit from conventional 
amplification devices such as hearing aids. 
• 
Mini-Mental State Exam (MMSE) score ≥23 for individuals with high-school degree 
or less; Mini-Mental State Exam (MMSE) score ≥25 for individuals with some 
college or more. Participants must be at risk for cognitive decline in the range 
quantified well by neurocognitive testing, and so must be free from more substantial 
cognitive impairment at baseline. 
• 
Willingness to participate, be randomized, and adhere to the protocol. Participants 
must be willing and able to consent to participate in the study, be willing to be 
randomized to either the Hearing intervention or to the Successful Aging intervention, 
and be willing to commit to adhere to the study protocol for the duration of the trial (3 
years of a randomly assigned intervention). 
4.2 
Exclusion Criteria 
Potential candidates for enrollment who meet one or more of the following criteria are excluded 
from participation in the study:  
• 
Self-reported disability in ≥2 Activities of Daily Living (ADLs)  
• 
Any self-reported hearing aid use in the past year. Trial participants will be 
randomized to hearing intervention or successful aging intervention and, therefore, 
participants cannot be receiving treatment for their hearing loss already.  
• 
ARIC participants only: Diagnosis of adjudicated dementia based on a previous 
ARIC visit or participant required a proxy to assist with completing informed 
consent and responding to questions at ARIC Visit 6 or 7.  
• 
Vision impairment (worse than 20/63 on MNREAD Acuity Chart). Participants who 
cannot see (with correction) well enough to complete the neurocognitive assessment are 
excluded. 
• 
Medical contraindication to use of hearing aids (e.g., draining ear). Because hearing 
aids will be the primary device used in the hearing intervention, participants with medical 
contraindications to hearing aid use are excluded. 
• 
Permanent conductive hearing impairment as determined by a difference in air 
audiometry and bone audiometry (“air-bone gap”) greater than 15 dB in 2 or more 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
15 
contiguous frequencies in both ears. Because the impact of a conductive (versus a 
sensorineural) hearing loss on cognitive functioning may potentially differ and 
programming for hearing aids differs for conductive hearing loss, participants with 
permanent conductive hearing loss are excluded from the trial. Participants with an air-
bone gap due to fluid in the ears or other resolvable medical issue may be enrolled in 
the trial following successful medical resolution of the cause of the air-bone gap (see 
Temporary Exclusion Criteria below). 
• 
Unwilling to wear hearing aids on a regular (i.e., daily or near daily) basis 
• 
No participants are excluded based on race or sex. 
Temporary Exclusion Criteria  
Participants determined to have a conductive hearing impairment as measured by a difference 
in air audiometry and bone audiometry (“air-bone gap”) greater than 15 dB in 2 or more 
contiguous frequencies in both ears are referred for medical follow-up. Should the cause of the 
air-bone gap be determined to be due to a temporary or treatable medical issue (e.g., fluid or 
wax in the ears), participants may be enrolled following resolution of the issue (i.e., air-bone 
gap). Participants with asymmetrical sensorineural hearing (≥20 dB at 2 adjacent frequencies or 
≥10 dB at 3 adjacent frequencies) or with other symptoms/signs concerning for a retrocochlear 
etiology based on the assessment of the audiologist will also not be eligible to participate until a 
medical clearance/evaluation is obtained.  
 
5 
Recruitment and retention 
The Operations Committee (see section 18.1) monitors recruitment and retention of participants. 
5.1 
Integration within ARIC-NCS 
The ARIC study is a large, biracial prospective cohort study that enrolled 15,792 participants 
aged 45-64 years from four US communities in 1987-1989: Jackson, MS, Forsyth County, NC, 
Washington County, MD, and Minneapolis suburbs, MN. The Jackson cohort was entirely 
African-American, and the Forsyth County site was about 15% African-American, with all other 
participants being primarily white. ARIC participants have received multiple assessments of 
cardiovascular risk factors, measurement of microvascular and macrovascular markers, 
cognitive testing, PET amyloid, and brain MRI over the last 30 years. The ARIC study is well 
described with over 1700 papers published in peer-reviewed journals. Details of the overall 
ARIC study design have been published3 and can also be found at 
https://sites.cscc.unc.edu/aric/. From 2011 to 2014, ARIC participants returned for Visit 5 (V5) 
as part of the ARIC Neurocognitive Study (ARIC-NCS) to evaluate midlife vascular risk factors 
as predictors of late-life cognitive impairment. Beginning in 2015, ARIC-NCS was jointly funded 
by NHLBI, NIA, NIDCD, and NINDS (Co-PI: Coresh/Mosley) to conduct ARIC-NCS Visit 6 (V6, 
2016-17) and Visit 7 (V7, 2018-19) that will consist of a neurocognitive battery, audiometric 
testing, and physical functional assessments. The ACHIEVE trial will be nested within ARIC-
NCS, and recruitment will occur directly during V7. As such, V6 and V7 data will be used to 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
16 
directly screen and recruit ARIC participants for ACHIEVE in parallel with participants also 
recruited de novo from the community.   
To maximize efficiency and minimize participant burden, overlapping assessments between the 
ACHIEVE baseline visit and ARIC-NCS Visit 7 will generally be collected only once and shared 
across studies. If ACHIEVE baseline is completed first, the remaining ARIC Visit 7 assessments 
will be completed at a later visit, but shared elements will be omitted from NCS since ACHIEVE 
baseline data without randomized treatment group will be shared with ARIC-NCS for approved 
uses. If ARIC Visit 7 is completed first, the ACHIEVE baseline visit must be completed within 2 
months to share overlapping data; otherwise a full ACHIEVE baseline must be completed at 
least 6 months after ARIC Visit 7. Overlapping items are identified in the schedule of 
assessments and further described in the manual of procedures (MOP).  
5.2 
Field centers 
Recruitment will be based at the four established ARIC field sites (Washington County, MD; 
Jackson, MS; Forsyth County, NC; Minneapolis suburbs, MN). Participants will be preferentially 
recruited from ARIC-NCS to increase efficiency through targeted recruitment and use of existing 
ARIC resources (previously collected data, etc.). Highly trained ARIC staff at the four field 
centers will be responsible for the recruitment of ACHIEVE participants. Conservative estimates 
based on recruitment rates during the ACHIEVE-P pilot study project that ~425 of the 850 
ACHIEVE participants will be from the ARIC-NCS study.  
George W. Comstock Center in Washington County, MD  
The George W. Comstock Center is a dedicated research facility, affiliated with the Johns 
Hopkins Bloomberg School of Public Health, where Washington County residents were 
recruited and followed for ARIC. The ARIC study as well as a number of other NIH-funded 
studies are conducted in the Comstock research facility which houses 30 employees in 
approximately 10,000 square feet of space dedicated to community-based research with 
multiple examination rooms, conference rooms, and research space. Dr. Coresh is the director 
of this Center. The Comstock Center is located in Hagerstown, Washington County, Maryland, 
75 miles from the Johns Hopkins University campus. The research center has handicap 
accessible entrances from the street, waiting rooms, examination rooms, interview rooms, 
phlebotomy and blood processing rooms with space for refrigerators and a freezer, lounge, 
conference rooms, file rooms, storage space, kitchens for preparation of snacks, and handicap 
accessible restrooms. The center has adjacent free parking. The Department of Epidemiology 
faculty and administrative staff oversee and advise on clinical and study conduct issues. The 
current project coordinator at the Center oversees space and staff sharing issues.  
The University of Mississippi Medical Center in Jackson, MS  
The University of Mississippi Medical Center (UMMC) has a long history of excellence in 
cardiovascular and neuro-epidemiologic research including recruitment and retention of African 
American participants for several large NIH-funded population-based studies (such as ARIC). 
The site has recruited and followed City residents for ARIC. The Memory Impairment and 
Neurodegenerative Dementia (MIND) Center was launched in 2010 at UMMC as a new initiative 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
17 
to elucidate the mechanisms and risk factors for brain aging and age-related diseases such as 
Alzheimer's. To enhance synergy across projects, cohort and clinical studies focused on aging 
and neurologic endpoints were brought together under the MIND Center umbrella. Dr. Mosley is 
the principal investigator for the ARIC Jackson Field Center at UMMC and the director of the 
MIND Center. Housed in the MIND Center, the ARIC Field Center is conveniently located on 
UMMC’s main campus. The ARIC Field Center includes 18,000 square feet of space including 
office, interview, and examination rooms. Facilities consist of a reception area and waiting room, 
multiple interview/procedure rooms, nurses' work station and office space, kitchen, storage 
areas with locking file cabinets, and phlebotomy and sample processing area with multiple -
70°C freezers. Parking is conveniently located immediately behind the building. A dedicated van 
is available to shuttle study participants to diagnostic facilitates on campus (e.g., MR imaging) or 
to conduct assessments in the participant’s home, if needed. In 2017, the MIND Center (and the 
ARIC Field Center) will move to a new state-of-the-art research building located on UMMC’s 
main campus (also, with convenient parking). The ARIC clinic space will be outfitted with new 
state-of-the-art equipment and has been ergonomically designed specifically to enhance 
research with older participants (e.g., equipped with high/low powered exam tables to facilitate 
transfer on/off the table, etc.). The ACHIEVE trial at UMMC will be conducted in this new space. 
University of Minnesota, Minneapolis, MN  
The ARIC Field Site in Minneapolis, located at the Epidemiology Clinical Research Center at the 
University of Minnesota has recruited and followed residents of selected Minneapolis suburbs 
for ARIC. Dr. Pankow is the site principal investigator for the ACHIEVE study. The Epidemiology 
Clinical Research Center (ECRC) is located one block away from the offices of the Division of 
Epidemiology and Community Health, about 0.5 miles from the University of Minnesota Hospital 
on the Minneapolis campus, and is readily accessible from all parts of the Twin Cities 
metropolitan area (within three blocks from two major interstate highways). The ECRC occupies 
one floor (17,758 square feet) of a two-story building and includes reception area, offices for 
staff, examination rooms, interview rooms, ultrasound, phlebotomy and blood processing rooms, 
freezer room, lounge, conference rooms, and storage space. The building meets current 
regulations for handicapped accessibility and has 100 free adjacent parking spaces. The site 
was established in February 2000 and is currently providing space and infrastructure for 25 
research projects including multi-center epidemiologic studies and clinical trials.   
Wake Forest University, Forsyth County, NC  
The Forsyth County ARIC Field Site is located at Wake Forest University. Dr. Hayden is the site 
principal investigator for the ACHIEVE study. The Public Health Research Center (PHRC) is the 
site for clinic examinations for County residents for ARIC and is located in the Piedmont Plaza I 
building on the Wake Forest University Baptist Medical Center campus. The PHRC provides 
investigators within the Division of Public Health Sciences with facilities and staff to perform 
multi-center clinical trials and observational research. The PHRC is easily accessible to all study 
participants as it is located on the ground floor of the Piedmont Plaza I Building, within a half 
mile of the main hospital, and is handicap accessible. With over 5,600 square feet of space, the 
PHRC has 18 rooms, a laboratory, a large waiting area, adequate parking that is free of charge, 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
18 
and many additional amenities to enhance the research experience of our participants. This 
clinic is equipped to handle all examinations and tests associated with the ACHIEVE clinical 
trial. 
5.3 
Recruitment strategies 
Each field site will implement a variety of strategies to achieve their recruitment targets with 
ACHIEVE participants being recruited both from ARIC-NCS and de novo from the surrounding 
communities. Recruitment of ARIC participants will occur concurrently with ARIC-NCS Visit 7 in 
close collaboration with the ARIC-NCS steering committee and as described in section 5.1. 
Recruitment of de novo participants will be from the surrounding ARIC field site communities. 
ACHIEVE field site PIs and field site staff have overseen recruitment of older adults for other 
epidemiologic clinical studies and will employ site-specific strategies that have demonstrated 
prior success with recruitment of older adults. Such strategies include: utilizing established 
research registries, targeted advertisements in aging-related publications/radio, established field 
site relationships with local churches/retirement centers, mass mailings, etc. 
5.4 
Retention strategies 
In order to maximize adherence, at the time of screening, only those participants who are 
determined by study personnel to fully understand the commitments of the study and are likely 
to follow the study protocol including regular use or not (as randomized) of a hearing aid are 
enrolled. Enrolling dedicated participants from those still attending ARIC examinations after 
nearly 30 years is likely to maximize study retention.   
The following procedures are implemented in order to enhance retention:   
• 
When scheduling the clinic visit, participants will be asked about: 
o Preferred time and date of examination  
o How participants prefer to get to the clinic visit 
o Need for assistance getting to or moving around the clinic  
o Existence of any medical conditions (e.g., diabetes, dietary restrictions) which 
might affect the examination and/or type of snack provided.  
• 
To enhance response following the scheduling telephone call by ACHIEVE staff, a 
packet will be mailed to the participant prior to the scheduled appointment. This pre-
appointment packet confirms the examination date and time and reviews the preparation 
procedures. Prior to the examination a reminder call will also be made to the participant. 
• 
Free parking is provided to all participants. Participants will be reimbursed for travel 
costs, or transportation will be covered for a participant if he/she is not able to drive 
and/or obtain a ride to attend a study visit. 
• 
Participant study incentives will include study-related items (pens, bags, mailed holiday 
cards) and/or modest payments (~$20) for participating in each study visit. Individual 
field sites will determine the participant incentives to provide based on their previous 
experience and knowledge of their participants and community.  
• 
Participants will be contacted by telephone to reschedule the appointment if eligible 
participants fail to arrive for a scheduled appointment or cancel their appointments.  

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
19 
• 
Home visits and telephone visits by study staff will be conducted as necessary when 
participants may be physically unable to come to the field site (e.g., from illness or 
injury). These visits will be informed by the experiences of study staff in performing such 
visits in ARIC-NCS Visits 5 and 6.  
• 
Participants randomized to the hearing intervention and successful aging intervention 
group will also be informed (and reminded throughout their study participation) that they 
will have the option of receiving the other intervention upon their completion of the study.  
• 
Each no-show case will be individually reviewed by the interviewer and when necessary 
by the supervisor. Efforts to engage the participant will include a combination of 
telephone contacts, letters, and the possibility of offering an abbreviated exam. Field site 
staff, in consultation with the study coordinator and/or field site PI and/or quality control 
committee, will determine how long to continue contact efforts. A participant will only be 
considered “withdrawn” if he/she explicitly requests to withdraw from the study. 
Participants are free to refuse or re-enter the study protocol after refusal at any time. 
 
6 
Participant rights and confidentiality 
6.1 
Informed consent 
A signed consent form is obtained from each participant. The consent form describes the 
purpose of the study, the procedures to be followed, and the risks and benefits of participation. 
The purpose of the informed consent form is: 
• 
To inform the prospective participant as much and as accurately as possible about: 
o The procedures involved in the study 
o What is expected of participants who consent to enroll 
o What the study can and cannot provide to the participant 
o What are the reasonable risks and benefits 
o What are the alternatives to participation 
• 
To document the participant’s consent to participate in screening, and all of the 
respective procedures involved. 
• 
To provide a prospective participant with a legal document summarizing the study and 
his or her rights as a study participant. 
• 
To provide the participant with ongoing explanations and continuing information that help 
the participant decide whether to begin or continue in the research study. 
 
Reobtaining consent in the event of cognitive impairment 
• 
Although those with dementia will not be enrolled at baseline, given the age of the cohort 
some participants may develop cognitive impairment over the course of the study. Those 
determined to have significantly reduced cognitive capacity during the trial and who wish 
to remain in the study will be re-consented with consent from a designated proxy to 
continue to participate in the study. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
20 
• 
If re-consent with a proxy is required, the re-consent may occur in person or remotely.  
Remote consent would be obtained by mailing two copies of the consent form to the 
proxy, having trained study personnel review the consent form with the proxy and 
participant over the telephone (answering questions and ensuring understanding), and 
having the proxy and participant sign one copy of the form and mail it back.  Upon 
receipt, the study personnel who obtained consent would sign the form and document 
the consent process in a note in the participant’s chart. 
• 
Classifying decision-making capacity is challenging and often task specific. Given the 
minimal risk associated with the study procedures, relatively conservative criteria will be 
used to trigger re-consent with a proxy. These include: (1) a diagnosis of dementia 
based on cognitive testing at any of the ACHIEVE exams or (2) judgment of our trained 
staff at the time of an exam. These criteria adhere to the published recommendations of 
the Alzheimer’s Association (Alzheimer Disease and Associated Disorders 2004; 
18:171-175). 
6.2 
Participant confidentiality 
Data from the ACHIEVE study are used only in aggregate, and no identifying characteristics of 
individuals will be published or presented. Results of select testing (weight, body mass index, 
and blood pressure) are given to participants, and they can choose to share those data with 
their health care provider. Alert values related to blood pressure or depression results are sent 
to participants’ private physicians, if participants agree, and are also sent to the participant. 
Information, including results of testing to be shared with a participant’s primary care physician, 
is not released without written permission of the participant, except as necessary for monitoring 
by IRB. 
Confidentiality of data is maintained by using research identification numbers that uniquely 
identify each individual. This study utilizes safeguards established as part of the parent study 
(ARIC) to ensure the security and privacy of participants’ study records. Research records are 
kept in locked file cabinets within locked rooms at the study site. Only selected study personnel 
will have access to participants’ study records on a need-to-know basis. Data are stored on 
password-protected computers with regularly updated virus software. Identifying information is 
only kept in the files where it is necessary for the conduct of the study and linkage to other files. 
In analysis files, only study IDs are used to identify participants.  
In compliance with the Health Insurance Portability and Accountability Act (HIPAA) and the 
Standards for Privacy of Individually Identifiable Health Information of the Department of Health 
and Human Services, ACHIEVE accesses personal health information and medical records only 
after receiving signed informed consent. Participants’ medical records that are obtained for 
review and abstraction are kept in a locked cabinet that is separate from other file cabinets. 
Only selected study personnel have access to these files. 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
21 
7 
Data collection and measurements 
7.1 
Audiometric assessment 
The audiometric diagnostic battery will be conducted by a trained audiologist for all participants, 
regardless of treatment assignment. The diagnostic battery is based on current American 
Academy of Audiology guidelines.4 Cerumen management by the study audiologist will be 
performed as needed. Participants with more severe cerumen impactions that cannot be easily 
cleared by the study audiologist will be provided with over-the-counter cerumenolytic ear drops 
(e.g., Debrox, Murine) and advised to follow-up with their primary care provider or an 
otolaryngologist.  
All audiometric testing will occur in a sound-attenuated booth. The WhisperRoom 
(www.whisperroom.com/) was chosen due to its small footprint and lower weight compared to 
traditional metal sound booths. 
 
7.1.1 Case history  
Audiological history including history of noise exposure, prior hearing aid use, etc. 
 
7.1.2 Air conduction audiometry 
Behavioral measurement of minimally perceptible tones tested across the frequencies most 
important for speech communication delivered through headphones. 
 
7.1.3 Tympanometry 
Objective measurement that determines integrity of the tympanic membrane/ossicles and 
assists in determination of a sensorineural hearing loss free of middle ear problems. 
 
7.1.4 Bone conduction audiometry 
Behavioral measurement of minimally perceptible tones tested across the frequencies most 
important for speech communication delivered through a bone oscillator, which allows 
determination of a sensorineural hearing loss free of middle ear problems. 
 
7.1.5 Word Recognition in Quiet 
Assesses the participant’s ability to repeat back monosyllabic words presented at a comfortable 
listening level, scored as percent correct, to confirm that the participant’s speech perception 
abilities are consistent with a hearing loss that can be helped through traditional hearing aid 
intervention.5 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
22 
 
7.1.6 Quick Speech in Noise (unaided) 
The QuickSIN is a speech-in-noise test that measures the signal-to-noise ratio (SNR) necessary 
for a listener to correctly identify 50% of key words on sentences presented in a babble 
background noise. A listener’s abilities to understand speech in noisy backgrounds cannot be 
predicted by the audiogram, and this measure provides a tool to counsel the patient on realistic 
expectations for success with hearing aids and guides intervention decisions regarding hearing 
assistive technology (e.g., remote FM microphone). [Development of the test article;6 Validation 
article7] 
 
7.2 
Cognitive battery 
7.2.1 Administration  
To assess cognitive decline and characterize dementia and Mild Cognitive Impairment (MCI), an 
efficient but comprehensive neuropsychological assessment will be administered by trained and 
certified examiners. The battery of cognitive measures (described below) are well-validated, 
standardized instruments that are widely used in clinical and epidemiologic studies of cognitive 
function and dementia, including ARIC-NCS, and include most of the measures recommended 
in the Uniform Data Set (UDS) implemented in 2005 across all National Institute on Aging-
sponsored Alzheimer's Disease Centers. 
A trained examiner administers the cognitive function tests in a fixed order, one right after the 
other, during a single session in a quiet room. To ensure that the participant understands each 
task, test instructions are presented verbally and visually (e.g., with a practice template or 
written instructions). The measures in the cognitive battery are briefly described below. Note 
that the MMSE (screener and secondary outcome) and WRAT (covariate) are also administered 
during the cognitive assessment and are described in sections 7.4.10 and 7.4.7, respectively. 
 
7.2.2 Ensuring speech understanding test  
Prior to performing the neurocognitive assessment, a brief test will be conducted to determine 
whether or not the participant can adequately hear the examiner. In this test, five sentences are 
read aloud to the participant by the psychometrist, and the participant is asked to repeat back 
the sentence. Participants are scored on the number of target words repeated back correctly (3 
target words/sentence). Steps on how to proceed with neurocognitive testing if audibility is not 
established are outlined in the MOP. 
The ACHIEVE Steering Committee developed this protocol to guard against poor speech 
understanding from hearing loss directly confounding administration of neurocognitive tests with 
auditory stimuli. This protocol was developed in collaboration with ACHIEVE Co-I’s with 
expertise in neuropsychology (Albert, Mosley, Knopman, Rebok) and audiology (Chisolm, 
Eddins) and was successfully pilot tested in the ACHIEVE pilot study.  

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
23 
 
7.2.3 Cognitive domains 
The ACHIEVE study will utilize the neurocognitive battery that was previously administered in 
ARIC-NCS8 (individual tests that constitute the battery are described in sections 7.2.4 – 7.2.13). 
Global cognitive function and three cognitive domains are derived from factor scores9 (see 
Section 12.3). These domains include:  
• 
Memory 
• 
Executive function 
• 
Language 
 
7.2.4 Delayed word recall test (DWRT) 
The DWRT is a measure of verbal memory that requires the participant to recall a list of 10 
common nouns following a short delay. The participant is presented with a stimulus card for 
each of 10 words. The examiner reads each word aloud, and asks the participant to repeat the 
word and use it in a sentence. This procedure is repeated, providing two exposures to the 
words. Following an approximate 5-minute delay, during which the (non-verbal) digit symbol 
substitution test (DSST) is given, the participant is asked to recall as many words as possible. 
Scores range from 0 to 10 words recalled. 
 
7.2.5 Digit Symbol Substitution test (DSST) 
The DSST is a measure of psychomotor speed and sustained attention. Besides its own value, 
the DSST also serves as a non-verbal distracter task, interposed between learning and recall for 
the DWRT above. The participant is asked to translate numbers (1-9) to symbols using a key 
provided at the top of the test form. The participant is provided with a pencil (without an eraser). 
Instructions are provided in a deliberate and slow pace. One point is given for each correctly 
drawn symbol completed within the 90-second time limit. Scores range from 0-93. 
 
7.2.6 Incidental learning 
The Incidental Learning Test was adapted from the Wechsler Adult Intelligence Scale, Revised 
as a Neuropsychological Instrument (WAIS-R NI) and provides a non-verbal measure of recent 
memory. Following the DSST, the participant is presented with the Incidental Learning 
Template. The participant is asked to write down as many of the DSST symbols as he/she can 
remember, in any order. Next, the participant is asked to write down the number that was paired 
with each of the symbols from the DSST. Two scores are yielded: 1) Free Recall: total number 
of symbols recalled, regardless of pairing and 2) Pairing: number of correct symbols correctly 
paired with corresponding numbers. Scores for each range from 0-9. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
24 
 
7.2.7 Trail Making Test Part A (TMT A) 
The TMT A is a timed task in which participants connect numbers in sequence as quickly as 
possible. TMT measures attention, sequencing, mental flexibility, and visual search and motor 
function. In TMT A, the participant is asked to draw a line and connect a series of numbers 
(from 1-25) as quickly as possible. Prior to the test part, the participant is given a sample test to 
demonstrate the task. The score for TMT A is the number of seconds required to complete the 
task. A maximum of 240 seconds (4 minutes) and 5 errors is allowed. 
 
7.2.8 Trail Making Test Part B (TMT B) 
The TMT Part B is a timed task in which participants connect letters and numbers in sequence 
as quickly as possible. TMT measures attention, sequencing, mental flexibility, and visual 
search and motor function. In TMT B, the participant is asked to draw a line and connect a 
series of numbers and letters, alternating between a given number and letter (e.g., 1 to A, A to 
2, 2 to B, B to 3, etc.) as quickly as possible. Prior to the test part, the participant is given a 
sample test to demonstrate the task. The score for TMT B is the number of seconds required to 
complete the task. A maximum of 240 seconds (4 minutes) and 5 errors is allowed. 
 
7.2.9 Logical Memory I and II 
This test, part of the Wechsler Memory Scale-Revised version, provides a measure of 
immediate and delayed verbal recall for the number of ideas presented in two stories, which are 
read to the participant. Two stories are read to the participant, each at a slow and deliberate 
pace. After each story is presented, the participant is asked to recall as much of the story as 
possible. The Logical Memory I score provides a measure of immediate recall and is calculated 
as the average number of ideas recalled from Story A and B. Each story contains 25 scoring 
units and the maximum score is 25.  
An approximate 20-minute delay follows, during which the remaining (non-memory) tests are 
administered. Following the delay period, the participant is again asked to recall the stories. The 
Logical Memory II score provides a measure of delayed recall and is calculated as the average 
number of story elements recalled from Story A and B. As each story contains 25 scoring units 
and the maximum score is 25. 
 
7.2.10 Digit Span Backwards 
Digit Span Backwards is part of the Wechsler Memory Scale-Revised and provides a measure 
of attention and working memory. The participant is read a series of numbers progressively 
increasing in length from two to eight digits. After the numbers are read, the participant is asked 
to repeat the numbers in the reverse order. Two trials at each digit length are performed (i.e., 2 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
25 
trials with 2 digits, 2 trials with 3 digits, etc.). The test is discontinued after two consecutive 
errors of the same length item. Scores range from 0-12. 
 
7.2.11 Boston Naming test 
The Boston Naming Test assesses visual naming ability using black-and-white drawings of 
common objects. For this study, the 30-item version used by the National Alzheimer's 
Coordinating Centers Uniform Data Set will be used. The participant is presented with a series 
of line drawings of objects and asked to name each object. The items become progressively 
more difficult based on their frequency of occurrence in the English language. A total score is 
calculated as the number of spontaneously produced correct responses. Scores may range 
from 0-30. 
 
7.2.12 Word Fluency 
The Word Fluency Test is a measure of verbal functioning. In this task, the participant is asked 
to produce as many words as possible that begin with the letters F, A, and S within a time limit 
of 60 seconds for each letter, avoiding proper nouns, variations, plurals, and repetitions. The 
score is the total number of admissible words produced across letters. 
 
7.2.13  Animal Naming 
Animal Naming is a measure of category fluency (semantic association). Category fluency, and 
specifically animal naming, is part of the Boston Diagnostic Aphasia Examination, the Stanford-
Binet test, and the CERAD. The participant is asked to name as many different animals as 
possible within a 60-second time limit. The score is given as the sum of all admissible names. 
 
7.3 
Dementia and MCI assessments 
A syndromic diagnosis of MCI and dementia will be determined and used as a secondary 
outcome. Current criteria for MCI10 and dementia,11 which were in part established by 
investigators for this project, are now well-established and have been employed successfully in 
ARIC-NCS. Details of the diagnostic procedures and normative data have been published and 
are enumerated in the MOP. Briefly, MCI and dementia syndromic diagnoses are determined by 
a panel of clinicians and neuropsychologists taking into account performance on the 
neuropsychological battery (test scores are compared to age, education, and race-specific 
norms), cognitive decline across study visits, and subject and informant interviews regarding 
cognitive functional status. Based on these elements, all examined participants have either a 
computer-algorithmic classification or an expert-adjudicated classification. The computer 
algorithm, also developed by the expert panel for ARIC-NCS, has been used successfully to 
enhance uniformity in applying the diagnostic criteria. In ARIC-NCS, the computer algorithm-

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
26 
reviewer agreement was high: 99% for normal, 94% for MCI, and 95% for dementia, suggesting 
that the algorithm accords well with clinical judgment. 
An MCI diagnosis is assigned in persons without dementia who meet all 3 criteria below: 
1. Cognitive decline in general cognitive performance, and  
2. At least one neuropsychological cognitive domain Z score < -1.5 Z, and 
3. Either Functional Activities Questionnaire (FAQ) score or Clinical Dementia Rating Scale 
(CDR) Sum of Boxes, not both, may meet threshold for impairment (these measures are 
described below in section 7.3.2 and 7.3.3). 
A dementia diagnosis is assigned by either: 
A) A low MMSE score (<21 for Caucasians or <19 for African-Americans), even in the 
absence of more complete cognitive testing or 
B) Meeting all three of the following criteria: 
1. Cognitive decline in general cognitive performance, and  
2. At least one neuropsychological cognitive domain scores < -1.5 Z, and 
3. CDR Sum of Boxes meets threshold for impairment and FAQ score may 
meet threshold for impairment. 
Participants failing to meet criteria for MCI or dementia are classified “normal”. 
The informant interviews noted above are conducted with a knowledgeable informant at every 
exam where the participants meet a priori criteria for poor cognitive performance and who have 
significant cognitive decline from prior exams. These measures are no longer collected once 
criteria for dementia are met. Participants who leave the study early will have procedures for 
ascertainment of dementia detailed in Section 7.3.5.  
 
7.3.1 Neurological interviews 
The neurologic interviews include the Clinical Dementia Rating Scale (CDR) and the 
Neuropsychiatric Inventory (NPI). In addition, the Functional Activities Questionnaire (FAQ) is 
used in determining a participant’s level of daily functioning, but does not have a dedicated 
interview or form; rather, all FAQ items are embedded within the CDR interview. Each of the 
measures are well-validated, standardized instruments that have been widely used in both 
clinical and epidemiologic studies of dementia. 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
27 
7.3.2 Clinical Dementia Rating Scale (CDR) 
The CDR gives important information about daily functioning, and is a required element in the 
determination as to whether an individual is demented or has MCI, or is normal. The CDR 
includes the CDR Participant (CDP), and the CDR Informant (CDI), and the CDR Summary 
(CDS).  
The CDP (the portion of the CDR administered to the participant) is administered to all 
participants. The CDP form is administered by a certified staff member to the participant while 
the participant is seated, and requires no equipment for administration.   
The CDI is administered by a certified staff member with a knowledgeable informant and can be 
administered in the clinic, if the informant is available, or may be collected by phone.   
After completion of these two components (and not in the presence of the participant or 
informant), a trained staff member will score the CDR (on the CDS form) based on the 
responses to the questions on both the CDP and CDI. The CDR scores range from 0 (normal) 
to 3 (severe impairment) for each of the following 6 areas: memory, orientation, judgment and 
problem solving, community affairs, home and hobbies, and personal care. The CDR Sum of 
Boxes sums over the 6 areas where each area score ranges from a 0 (normal function), 1 (has 
difficulty, but does by self), 2 (requires assistance), to 3 (dependent). A CDR Sum of Boxes >3 
indicates impairment. 
 
7.3.3 Functional Assessment Questionnaire (FAQ) 
There are 9 items from the informant interview of the CDR which are also FAQ questions (there 
are 10 FAQ questions; one CDR question encompasses two FAQ questions). The FAQ score is 
calculated by summing the 9 individual items (1 item is added twice). Scores per item range 
from a 0 (normal function), 1 (has difficulty, but does by self), 2 (requires assistance), to 3 
(dependent). An FAQ score >5 indicates impairment. 
 
7.3.4 Neuropsychiatric Inventory (NPI) 
The NPI consists of questions relating to personality and behavioral changes commonly seen in 
dementia. This scale is completed with a knowledgeable informant after the CDI, either in clinic 
or by telephone.   
 
7.3.5 Characterization of participants who leave the study early 
A final interview will be attempted with all participants who are either unable (e.g., due to illness) 
or unwilling to complete the study. Trained interviewers will collect information by telephone 
regarding the reason for withdrawal and offer to schedule a home visit for an abbreviated final 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
28 
exam. In the absence of a final home exam, because dropouts may be more likely to have 
dementia, we will attempt to ascertain dementia status using a telephone-based assessment 
with the participant or informant interview conducted with a knowledgeable informant.  
In the case where the participant is alive and able to communicate by phone, we will administer 
the Six Item Screener (SIS). The SIS is a short instrument developed to identify cognitive 
impairment in older adults. In the case where the participant has died or is otherwise unable to 
communicate by phone, dementia status may be characterized by informant interview via 
telephone using the AD8--a brief instrument, derived from the Clinical Dementia Rating Scale, 
developed to discriminate between normal aging and dementia. Notably, these procedures 
parallel ARIC’s ongoing dementia surveillance methods. For ARIC participants, additional 
sources of information may also be used to complete ascertainment of dementia cases (e.g., 
discharge codes from hospitalizations, CMS, and ICD codes on death certificates). 
 
7.4 
Inclusion/exclusion/covariates 
7.4.1 Demographics questionnaire 
This is an interviewer-administered questionnaire given to de novo participants to gather age, 
sex, employment status, race, ethnicity, education, and marital status. 
 
7.4.2 Health history questionnaire 
This is an interviewer-administered questionnaire given to each participant, which documents a 
number of chronic diseases or conditions (e.g., hypertension, diabetes, stroke, Parkinson’s 
disease, osteoporosis, among others). The collection of a medical history on each participant 
permits the assessment of overall health.  
 
7.4.3 Neurologic History  
This questionnaire includes items about past neurologic diagnoses and treatments. This 
information will be used as possible covariates and by MCI/dementia adjudicators.  
 
7.4.4 Anthropometry 
Participant height and weight will be measured using standardized study protocols from the 
parent study (ARIC). These are detailed in the MOP. Anthropometric measures include height, 
weight, waist and hip circumference, and body fat. These measures may be used to assess the 
risk of disease.  
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
29 
7.4.5 Seated blood pressure 
Seated systolic and diastolic blood pressure will be measured using standardized study 
protocols from the parent study (ARIC). These are detailed in the MOP. 
 
7.4.6 Blood draw 
A blood draw for ApoE ε4 genotyping in non-ARIC participants in ACHIEVE will be conducted at 
baseline and done using standardized study protocols. ARIC participants have previously had 
ApoE genotyping performed. 
 
7.4.7 Wide Range Achievement Test (WRAT) 
The WRAT is a widely used measure of academic achievement and commonly used to provide 
an estimate of premorbid functioning in adults with neurological conditions. In addition to 
education level, scores on the WRAT Reading subtest will be taken into account by 
Dementia/MCI reviewers when interpreting neuropsychological tests results. Following brief 
instructions, the participant is handed a test card and asked to read the words on the card 
aloud. Responses are recorded on the paper form. The test is discontinued following 5 
consecutive errors. Scores range from 0-70. 
 
7.4.8 Pure-tone audiometry (screening) 
Air conduction audiometry is conducted to see if the participant meets the audiometric inclusion 
criteria. Confirmatory audiologic testing performed by an audiologist is conducted during the 
baseline assessment.  
 
7.4.9 Vision screening 
This test is to determine the smallest print the participant can read. The MNREAD Acuity Chart 
is used as the vision screener. Full details can be found in the MOP. 
 
7.4.10 Mini-Mental State Exam (MMSE) 
The MMSE was developed as a brief, standardized instrument for screening a limited number of 
cognitive functions.12 We will use the MMSE to exclude those with significant cognitive 
impairment at baseline and to track cognitive decline and dementia during study follow-up. The 
MMSE is administered by interview. A detailed script is provided for each item and task. Scores 
range from 0-30. 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
30 
7.4.11 Activities of Daily Living (ADL) 
Assessed by an interviewer-administered questionnaire, ADLs assess a person’s ability to 
perform basic activities of daily living (e.g., getting in/out of bed or chairs, bathing, dressing, 
eating, toileting). 
 
7.4.12 COVID impact questionnaire 
Added in January 2021, this brief questionnaire asks questions about how the coronavirus 
pandemic, or COVID-19, have affected the participant. 
 
7.5 
Other pre-specified outcomes 
7.5.1 Center for Epidemiological Studies Depression and Hopelessness Scale (CES-D) 
Depressive symptoms have been linked to a number of important health outcomes including 
cardiovascular disease risk factors, coronary heart disease morbidity and mortality, cognitive 
functioning, and MCI/dementia. In ACHIEVE, depressive symptoms will be assessed using the 
Center for Epidemiologic Studies Depression Scale (CES-D) Short Form. The CES-D Short 
Form is derived from the original 20-item CES-D.13 In addition to a reduced administration time 
and clearer response options (relative to the 20-item version), the Short Form is highly 
correlated with the original (r > .94), has a high internal consistency, retains the same factor 
structure as the original, and has a similar positive predictive value as a screening tool for 
identifying clinical depression. It takes approximately 3 minutes to complete this 12-item 
questionnaire. The questionnaire is administered by interview. As a scale for depression, 
responses must be provided by the participant, not a proxy. Because of the sensitive nature of 
some of the questions, interviewers must take care to ask questions and record responses in a 
sensitive and non-judgmental manner. Most of the questions are self-explanatory; however, if 
the respondent is unclear, the interviewer will repeat the question and use general phrases, 
such as: “Answer as best you can, based on how you have felt over the past week.” 
Interviewers should not lead participants to an answer but remain neutral. Participants are 
asked to rate each item on a 3-point scale (scored 0 to 2) on the basis of “how often you have 
felt this way during the past week.” Response categories are:  
- Hardly ever or never (scored as 0)  
- Some of the time (scored as 1)  
- Much or most of the time of (scored as 2)  
Positively worded items are reverse-coded, and a total score is calculated as the sum of the 
responses to questions 1-11. Total scores range from 0 to 22, with higher scores indicating 
greater expression of depression. The 12th item is a rating of hopelessness that is not included 
in the total score. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
31 
 
7.5.2 Baecke Physical Activity Questionnaire  
This is an interviewer-administered questionnaire14 given to each participant that measures the 
frequency and duration of self-reported activities, which is currently used in ARIC. This 
questionnaire asks about habitual physical activities including sport-related activities during 
leisure time, non-sport related physical activity during leisure time, and television viewing. 
Composite scores of sport during leisure time and leisure time excluding sport are generated as 
continuous measures each ranging from 1 to 5. 
 
7.5.3 Hearing Handicap Inventory for the Elderly – Screening Version 
This is an interviewer-administered questionnaire given to each participant to gather data on the 
perception of the impact of hearing loss.15 This questionnaire assesses the social and emotional 
components of perceived hearing impairment such as embarrassment, and limits on personal 
and social life.  
 
7.5.4 RAND 36-Item Health Survey 
The RAND-36 Health Survey is an interviewer-administered scale that assesses health-related 
quality of life (HRQL).16 It is a generic measure, as opposed to one that targets a specific age, 
disease, or treatment group. Physical health and mental health component scores are each 
derived using factor analysis, with mean of 50 and standard deviation (SD) of 10 (range 0 to 
100, with higher scores indicating better health). 
 
7.5.5 Social Network Index  
The Cohen Social Network Index (SNI) is an interviewer-administered questionnaire given to 
each participant to gather social network data.17 The Social Network Index evaluates two 
outcome variables: (1) Social Network Diversity – Number of social roles in which the participant 
had regular contact with for at least once every 2 weeks, and (2) People in Social Network – 
Total number of people with whom the participant had regular contact (at least once every 2 
weeks). Examples of items include “How many other relatives (other than your spouse, parents 
& children) do you feel close to?”, “Do you attend any classes (school, university, technical 
training, or adult education) on a regular basis?”, “Are you currently involved in regular volunteer 
work?”, among others. 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
32 
7.5.6 UCLA Loneliness Scale 
This is an interviewer-administered questionnaire given to each participant to gather loneliness 
data.18 This 20-item questionnaire measures subjective ratings of social isolation and loneliness 
(e.g., lacking companionship, feeling left out, and isolated from others, among others) using a 4-
point Likert scale. Positively worded items are reverse-coded, and an average score ranging 
from 1 to 4 is generated, with higher scores indicating greater expression of loneliness. 
 
7.5.7 Accelerometry 
Physical activity is objectively assessed using the Actigraph Link accelerometer, an FDA 
approved, triaxial, water-resistant, wrist-worn device that can be worn 24 hours a day, 
continuously measuring intensity, duration, and frequency of physical activity. Participants will 
be fitted with the device during their clinic visit and asked to continue wearing the device at all 
times for the subsequent 7 days.19 Participants will be asked to wear the accelerometer at 
baseline and again at follow-up to detect differences in physical activity and sedentary 
behaviors.  
 
7.5.8 Falls and mobility 
This is an interviewer-administered questionnaire given to each participant to record living 
circumstances, self-reported physical ability, fatigue, and falls. 
 
7.5.9 Hospitalizations 
This is an interviewer-administered questionnaire given to each participant to record recent 
hospitalizations since the last time of study contact. 
 
7.5.10 Grip strength 
Grip strength will be measured using standardized study protocols from the parent study 
(ARIC). These are detailed in the MOP. Grip strength (kg of force) is objectively assessed with a 
hand-held dynamometer. After one practice trial, participants are asked to complete two trials, 
squeezing as hard as possible, with a 15-20 second rest between trials. Grip strength is not 
completed for those who have had surgery on both hands or on both wrists in the previous 3 
months. If only one side is affected, the unaffected side is tested. The test can be performed if 
the participant has a current flare-up of pain in their wrist or hand, for example arthritis or 
tendonitis. This information is recorded on the data collection form. 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
33 
7.5.11 Short Physical Performance Battery (SPPB) 
The Short Physical Performance Battery20 will be conducted using standardized study protocols 
from the parent study (ARIC). These are detailed in the MOP. The SPPB is a series of physical 
performance tests designed to assess lower extremity function in older adults. The SPPB 
ranges in score from 0-12; higher scores indicate better function. The total score is the sum of 3 
component scores: chair stands, balance, and 4-meter walk; each component score ranges 
from 0-4. Exclusion from any performance test is based on examiner assessment or participant 
concerns that the test would be unsafe. Walking aids are allowed during the 4-meter walk only, 
if participants feel they are necessary. 
 
7.5.12 Intervention Feedback Form 
This gathers feedback about the study intervention that participants are receiving. Participants 
rate how strongly they agree or disagree with a series of statements about the ACHIEVE study 
intervention they received. 
 
7.6 
Communication partners assessments 
Communication partners (e.g., spouse) of participants randomized to the hearing intervention 
group are invited to join the study and contribute data related to their own quality of life and their 
observations of the effects of the hearing intervention on the participant. Communication 
partners are adults (18+ years) who communicate with the participant on a daily or near-daily 
basis. Informed consent is obtained during the 1-2 months after randomization when the hearing 
intervention participant is receiving the first 2 study intervention visits which the communication 
partner may also be attending in a supportive role. Demographic data will be gathered at 
enrollment, and health-related quality of life data (RAND36; 7.5.4) and data on the 
communication partner’s observations of the effects of the hearing intervention on the 
participant (International Outcomes Inventory – Significant Other) will be gathered semi-annually 
to annually. Individuals who are also enrolled in the ACHIEVE study as a randomized participant 
are not eligible to also be enrolled/consented as a communication partner in the ACHIEVE study 
for another randomized participant (e.g., spousal pairs randomized as a dyad to the hearing 
intervention group). If the communication partner can no longer participate, data collection for 
the communication partner will end. Participants are welcome to invite a new communication 
partner to join them at the study visits but no data will be gathered from this communication 
partner. 
 
7.7 
Schedule of evaluations 
Table 3 details when data will be gathered. Data collection visits may be split across multiple 
days or multiple settings (clinic visits, home visits, telephone contacts, or video calls) to meet 
the needs of our participants. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
34 
Table 3. Schedule of Evaluations 
Assessment 
Pre-
screening 
Screening  Baseline 
Intervention and Follow-Up Visits 
Visit 0 
Visit 1 
Visit 2  Visit 3  Visit 4  Visit 5 
Visit 6  Visit 7  Visit 8  Visit 9 Visit 10 Visit 11 
(Day -31 
to Day 0) 
Day 0 
(W1-3) (W3-5) (W6-8) (W8-10) (6mo) (12mo) (18mo) (24mo) (30mo) (36mo) 
A 
B 
C 
D 
 
Yr1 
 
Yr2 
 
Yr3 
Inclusion Criteria and Covariates 
Informed Consent   
 
X 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X1 
 
X 
 
 
 
 
 
 
 
 
 
 
Health History Form 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
Hearing and Noise exposure 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Vision Screening 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Activities of daily living 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Anthropometry 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Seated blood pressure 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Blood draw for ApoE 
 
 
X1,3 
 
 
 
 
 
 
 
 
 
 
WRAT 
 
 
X1 
 
 
 
 
 
 
 
 
 
 
Neurologic history 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
Audiometry 
Air conduction audiometry 
X1 
X 
 
 
 
 
 
 
X 
 
X 
 
X 
Bone conduction audiometry 
 
X 
 
 
 
 
 
 
X4 
 
X4 
 
X4 
Tympanometry 
 
X 
 
 
 
 
 
 
X 
 
X 
 
X 
Word Recognition in Quiet 
 
X 
 
 
 
 
 
 
X 
 
X 
 
X 
Quick Speech in Noise (unaided) 
 
X 
 
 
 
 
 
 
X 
 
X 
 
X 
Neurocognitive Battery 
Ensuring speech understanding 
test 
 
 
X2 
 
 
 
 
X 
X 
X 
X 
X 
X 
MMSE 
 
X2 
X2 
 
 
 
 
X 
X 
X 
X 
X 
X 
Delayed Word Recall Test 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Digit Symbol Substitution Test 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Incidental Learning 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Trail Making Test Part A 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Trail Making Test Part B 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Logical Memory 1 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Logical Memory 2 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Digit Span Backward 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Boston Naming Test 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Word Fluency (FAS) 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Animal Naming 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Non-Neurocognitive Measures 
Clinical Dementia Rating Scale - 
Participant (CDP) 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
Dementia/MCI evaluation if 
applicable5 (CDI, CDS, NPI) 
 
 
X5 
 
 
 
 
 
X5 
 
X5 
 
X5 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
35 
Assessment 
Pre-
screening 
Screening  Baseline 
Intervention and Follow-Up Visits 
Visit 0 
Visit 1 
Visit 2  Visit 3  Visit 4  Visit 5 
Visit 6  Visit 7  Visit 8  Visit 9 Visit 10 Visit 11 
(Day -31 
to Day 0) 
Day 0 
(W1-3) (W3-5) (W6-8) (W8-10) (6mo) (12mo) (18mo) (24mo) (30mo) (36mo) 
A 
B 
C 
D 
 
Yr1 
 
Yr2 
 
Yr3 
Adverse event assessment/ 
Unanticipated problems 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CES-D Scale 
 
 
X2 
 
 
 
 
X 
X 
 
X 
 
X 
Hearing Handicap Inventory for 
the Elderly - Screening Version 
 
 
X2 
 
 
 
 
X 
X 
 
X 
 
X 
RAND 36-Item Health Survey 
 
 
X 
 
 
 
 
X 
X 
 
X 
 
X 
Cohen Social Network Index 
 
 
X 
 
 
 
 
X 
X 
 
X 
 
X 
UCLA Loneliness Scale 
 
 
X 
 
 
 
 
X 
X 
 
X 
 
X 
Accelerometry 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
Falls and mobility questionnaire 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
Hospitalizations 
 
 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
Grip Strength 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Short Physical Performance 
Battery 
 
 
X2 
 
 
 
 
 
X 
 
X 
 
X 
Physical Activity Form 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
Intervention feedback form 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
COVID impact questionnaire6 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
SUCCESSFUL AGING INTERVENTION PARTICIPANTS ONLY 
Successful aging intervention 
visit/booster session 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
HEARING INTERVENTION PARTICIPANTS ONLY 
Hearing Intervention Assessment Outcomes 
Real-ear aided response 
 
 
 
 
X 
X7 
X7 
X7 
 
X7 
 
X7 
 
Speech Intelligibility Index 
(aided) 
 
 
 
 
X 
X7 
X7 
X7 
 
X7 
 
X7 
 
Quick Speech in Noise (aided) 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
Hearing Aid Data Log 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
International Outcome Inventory 
for comprehensive intervention 
 
 
 
 
 
 
X 
X  
X 
X 
X 
X 
X 
Client-Oriented Scale of 
Improvement 
 
 
 
X 
 
X 
X 
 
 
 
 
 
 
COMMUNICATION PARTNERS FOR PARTICIPANTS RANDOMIZED TO HEARING INTERVENTION 
Informed Consent Form   
 
 
 
X8,9 
X8,9 
 
 
 
 
 
 
 
 
Demographics 
 
 
 
X8,9 
X8,9 
 
 
 
 
 
 
 
 
RAND 36-Item Health Survey 
 
 
 
X8,9 
X8,9 
 
 
X9 
X9 
 
X9 
 
X9 
International Outcome Inventory 
– Significant Other 
 
 
 
 
 
 
X9 
 
X9 
 
X9 
 
X9 
1. Procedures only needed for participants not in ARIC-NCS. 
2. Measures shared across ACHIEVE and ARIC-NCS V7. 
3. Typically obtained at the baseline visit, but could be obtained at a follow-up visit if not obtained at the baseline visit. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
36 
Assessment 
Pre-
screening 
Screening  Baseline 
Intervention and Follow-Up Visits 
Visit 0 
Visit 1 
Visit 2  Visit 3  Visit 4  Visit 5 
Visit 6  Visit 7  Visit 8  Visit 9 Visit 10 Visit 11 
(Day -31 
to Day 0) 
Day 0 
(W1-3) (W3-5) (W6-8) (W8-10) (6mo) (12mo) (18mo) (24mo) (30mo) (36mo) 
A 
B 
C 
D 
 
Yr1 
 
Yr2 
 
Yr3 
4. Only required at initial hearing test or follow-up visits if there has been a change in pure-tone air conduction. 
5. Collected if participant is selected for informant interview, identified on the Selected to Stage 2 report in the study database. 
6. Added in January 2021. 
7. Only required when the participant needs a programming adjustment in the software.  
8. Only needs to be completed once at either visit A or B. 
9. Only completed if communication partner is present for the visit and willing to participate. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
37 
8 
Randomization 
Randomization, stratified by ARIC study status, field center, and hearing impairment level is 
completed within the Carolina Data Acquisition and Reporting Tool (CDART) web-based data 
management system. Although ACHIEVE hearing aid intervention is by nature un-masked, in 
order to minimize bias based on review of accumulating data by the project team, the ACHIEVE 
PI, co-investigators, and key project staff except Data Coordinating Center staff and one 
unblinded statistician will remain blinded to accumulating data by treatment group. 
• 
The intervention group to which a participant is assigned is determined by an allocation 
schedule developed by the Data Coordinating Center. 
• 
After final determination of eligibility and confirmation of informed consent, each 
participant will be randomized in a 1:1 ratio to either the hearing intervention or to the 
successful aging intervention. To ensure balance between the treatment groups, 
participants will be randomized in permuted order blocks of varying sizes within strata 
defined by severity of hearing loss, defined as mild (PTA ≥ 30 dB HL and < 40 dB HL) or 
moderate (PTA ≥40 dB HL and < 70 dB HL), participant status (ARIC or non-ARIC 
participant), and by field site. Block size will not be revealed to field center staff as this 
would allow them to determine the final treatment assignment of a block before 
ascertaining eligibility and obtaining consent. 
• 
Randomization will be performed at the end of the baseline visit. 
• 
When spouses or cohabitating partners are both eligible and randomized together, they 
will be randomized as a unit with, arbitrarily, the first spouse/partner of the pair to be 
selected according to the random assignment procedure and the second spouse/partner 
of the pair receiving the same assignment. Spouse/partner pairs will be randomized in 
spouse/partner-pair specific permuted order blocks of varying sizes within strata defined 
by participant status (at least one spouse/partner pair in ARIC or both non-ARIC 
participants) and by field site.  
 
9 
Interventions 
9.1 
Hearing intervention 
The conceptual framework for the development of the manualized patient-centered, best-
practices hearing intervention was the World Health Organization’s International Classification 
of Functioning, Disability and Health (ICF, http://www.who.int/classifications/icf/en/). The ICF 
focuses on a person’s ability to engage in activities and participate in life situations, as impacted 
by changes in body structures and/or functions, and influenced by environmental and personal 
contextual factors. The main objective of intervention is improving a person’s quality of life by 
eliminating or minimizing activity limitations and participation restrictions. To reach this objective 
the hearing intervention includes the identification of individual needs, the setting of specific 
goals, engagement in shared-informed decision-making, and the development of self-
management abilities.  

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
38 
The hearing intervention (HI) steps were developed from review of the most current and 
comprehensive evidence-based practice guideline for the rehabilitative treatment of hearing loss 
in adults published by the American Academy of Audiology (AAA) in 2006, along with 
consideration of subsequent research. An outline of the ACHIEVE-HI components was reviewed 
by an expert panel of audiologists (including M. Valente, L. Humes, H. Solodar, and R. McArdle 
among others) during a meeting in Tampa, FL in December 2014. Recommended modifications 
were incorporated into the hearing intervention, which was utilized in a feasibility study 
conducted at the University of South Florida with 20 older adult participants and initiated in May 
2015. The results of implementation in the feasibility study guided the use of the hearing 
intervention in the subsequent ACHIEVE-P randomized pilot study which was initiated at the 
Washington County, MD ARIC field site in August 2015. Experiences of study participants and 
site staff from both the feasibility and pilot studies were used to revise the hearing intervention, 
and this revised protocol was then reviewed in a face-to-face meeting of ACHIEVE investigators 
and an external expert audiology consultant, C. Palmer in April 2016. Recommendations for 
clarification were incorporated into the final hearing intervention protocol which is included in the 
MOP. 
The hearing intervention consists of 4 sessions (Sessions A-D, each session ~1 hr) spaced over 
the 2-3 months post-randomization and are designed to provide all of the active components of 
the intervention. Audiologic outcomes (e.g., hearing aid data logging, real ear measures, speech 
in noise, etc.) to verify the best-practices hearing intervention are gathered semi-annually 
beginning at 6 months post-randomization. Communication partners (CP) are often a key to 
success to intervention for older adults with hearing loss and are encouraged to attend the 
hearing intervention sessions.   
Session A is focused on the identification of individualized goals utilizing the Client Oriented 
Scale of Improvement (COSI) and the fitting of hearing aids (Session A). In addition to standard 
audiometric testing conducted in all ACHIEVE participants at baseline, an auditory needs 
assessment, involving specialized behavioral and self-report assessments, is completed in 
order to determine patient-specific recommendations for hearing aid intervention, including 
determination of signal processing and features (e.g., directional microphones, direct auditory 
inputs, noise management programs, frequency modulation [FM] devices, Bluetooth streaming, 
etc.). Participants will be fit binaurally with substantively equivalent technology that is currently 
found in Phonak Audéo V90-312T receiver-in-the-canal (RIC) hearing aids. Specification for 
hearing aid fitting and verification can be found in the MOP. Participants will be provided with 
materials to support self-management of hearing loss and communication in real-world settings, 
via the hearing intervention Toolkit (full details in MOP). The toolkit materials were developed 
based on previous research by Hickson and colleagues and with consideration of variations in 
health literacy, and cover the following topics: understanding hearing loss, realistic expectations, 
communicating in quiet, listening at a distance, communicating in background noise, using 
communication strategies and tactics, and resources for adults with hearing loss and their 
communication partners. The written materials are supplemented with a series of reusable 
learning objects (e.g., video clips) entitled C2HEAR which are designed to support first-time 
hearing aid users while they adapt to using hearing aids.  

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
39 
Session B occurs approximately 1-3 weeks after hearing aid fitting in order to allow for 
acclimatization to occur. If modifications are needed to the hearing aid fitting, they can occur 
and be documented in this or any subsequent sessions. During Session B, informal assessment 
of progress toward goals will be determined and needs for various hearing assistive 
technologies (HATs) will be assessed. HATs provide a more direct coupling of the sound source 
to the hearing aid, minimizing the negative effects of distance and background noise. Additional 
materials to support self-management are provided.  
Session C occurs approximately 1-3 weeks after Session B. Short-term hearing aid outcomes 
are assessed and individually selected HATs are dispensed. Each participant will receive at 
least one HAT, depending on his or her specific goals, and outcomes of hearing aid use. These 
HATs may include the following or generally equivalent devices: Phonak ComPilot II (streaming 
device); Phonak ComPilot Air II (streaming device); Phonak TVLink II; Phonak clip-on mic; 
and/or the Phonak Roger System. Systematic orientation to HAT use is provided and additional 
self-management tools are dispensed.  
Session D occurs approximately 1-3 weeks after Session C. Short-term outcomes of the 
comprehensive intervention approach, including use of hearing aids, HATs, and development of 
self-management skills, are assessed. Additional materials as needed to support self-
management are provided as well as a supply of batteries.  
Booster Intervention/Interim Visits: Scheduled semi-annual visits will capture audiologic 
outcomes and verify that hearing aids and HATs are functioning properly. Re-instruction in use 
of devices and hearing rehabilitative strategies will be provided during these visits. Booster 
sessions may be offered in a group format to allow for group rehabilitation for participants who 
are interested. We anticipate that unscheduled interim visits may also be required periodically 
(e.g., hearing aid malfunction), and these visits to trouble-shoot and/or repair malfunctioning 
hearing aids and/or HATs will be scheduled as needed if the issue cannot be resolved through a 
telephone conversation. 
Full details of the hearing intervention can be found in the MOP. 
 
9.2 
Successful Aging intervention 
Overview 
The successful aging health education control intervention (Successful Aging intervention, or SA 
intervention) will follow the protocol and materials developed for the 10 Keys™ to Healthy Aging 
program by the Center for Aging and Population Health Prevention Research Center at the 
University of Pittsburgh.1 This interactive, dynamic program informs older adults about risk 
factors for diseases. This program was developed from evidence-based research and aims to 
target the causes of disease and disability that could be greatly reduced, postponed, or 
eliminated to promote successful and healthy aging in functional older adults. The Successful 
Aging intervention contains the most up-to-date prevention guidelines available based on the 
current recommendations from leading groups such as the United States Preventive Services 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
40 
Task Force, Centers for Disease Control, and Institute of Medicine. Many adults age with more 
than one medical condition. A holistic approach to health provides a broad range of 
opportunities for individuals to become engaged and involved. This is important as the 
Successful Aging intervention focuses on the health and well-being of the whole person. 
Although the original “Keys” had 10 domains, the “Social Contact” Key will not be used (to avoid 
crossover effects with the main hearing loss intervention being tested), and a “Caregiving and 
Health” Key will instead be used for individuals for whom the smoking Key is not applicable. 
Individual participants in the Successful Aging intervention group will receive educational 
information and materials on health-related topics relevant to older adults. As a participant in the 
Successful Aging intervention, each individual will have an opportunity to practice skills and 
learn about: the importance of preventing disease and disability, information on Keys or health 
topics of his/her choice, and personal risk factors. In general, participants will receive 
information on a variety of health topic areas of relevance to older adults and learn how to 
actively “take charge” of their health and well-being in seeking out appropriate medical 
information, services, and resources. The health educator will tailor the Successful Aging 
intervention to each participant and provide guidance through the educational materials and 
ongoing support and encouragement over the duration of the study.  
At the first intervention visit, using a Prevention in Practice (PIP) report, the interventionist will 
present an introduction to all of the Keys and support the participant in identifying the specific 
topics of importance. At the first visit the interventionist will also go through the lowering systolic 
blood pressure key (this key was identified as the most popular key by Dr. Glynn and 
colleagues). Additionally, the interventionist will teach the participant proper technique for a 
series of upper body stretches. The second, third and fourth intervention sessions will contain a 
recap of the previous session and a new key. The participant will also do their body stretching 
routine. Each session will last approximately one hour, and each Key is designed to be 
presented during this time. Regardless of the specific Key being presented, each session will 
include a didactic education component as well as activities, goal-setting, and homework 
assignments to be completed by the following session.  
Specific Successful Aging Module Options 
Each participant randomized to the Successful Aging intervention will have the opportunity to 
cover the following Keys or health topics: 
 
Key #1: Lower Systolic Blood Pressure 
Key #2: Stop Smoking (if the participant is a smoker; if the participant is not a smoker 
they will skip this key) 
 
Key #3: Participate in Cancer Screening 
 
Key #4: Get Immunized Regularly 
 
Key #5: Regulate Blood Glucose 
 
Key #6: Lower LDL Cholesterol 
 
Key #7: Be Physically Active 
 
Key #8: Maintain Healthy Bones, Joints, and Muscles 
 
Key #9: Combat Depression 
 
Key #10: Caregiving and Health 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
41 
Contact Mode and Frequency 
Participants randomized to this group will meet individually with a health educator certified to 
administer the program every 2-3 weeks for a total of 4 visits over about 2-3 months. This 
program was effectively piloted in this cohort and previously implemented by Dr. Glynn in the 
Aging Successfully with Pain RCT.21,22 To further enhance retention and perceived benefit, each 
session will also include a 5-10 minute active upper body extremity stretching program as used 
in the Lifestyle Interventions and Independence for Elders (LIFE) study.2 Participants will return 
for booster sessions semi-annually (+/- about one month). Session content for booster sessions 
will be keys 5-9 (or 6-10 for non-smokers). The upper body stretching program will also be 
implemented during the booster sessions.  
Visit 1 (Session A):  Weeks 1-3 
Visit 2 (Session B):  Weeks 3-5 
Visit 3 (Session C):  Weeks 6-8 
Visit 4 (Session D):  Weeks 8-10 
 
Participants who miss a scheduled visit will be contacted by intervention staff to reschedule or to 
assist with overcoming barriers to attendance (e.g., transportation). Additional support will be 
provided by aging experts from the University of Pittsburgh who have years of experience 
overcoming barriers associated with adherence to the program.  
 
Full details of the Successful Aging intervention can be found in the MOP. 
 
10 Strategies to promote intervention adherence/compliance & minimize bias from 
unblinded study participants and staff 
Adherence to the study intervention will be assessed at each study visit using questions 
designed to capture adherence in both the hearing and successful aging intervention groups. 
Strategies for Promoting Adherence in the Hearing Intervention 
Strategies to promote adherence in the Hearing Intervention include: 
• 
Expectations of potential benefits of the intervention are structured given the 
participant’s level of hearing impairment in order to ensure that participants’ expectations 
are reasonable and realistic. 
• 
Individual assessment and instruction. 
• 
Participants are asked to bring a communication partner with them to the intervention 
visits. 
• 
Repeated assessment of individualized hearing goals with the audiologist and 
development of strategies to meet those goals throughout the intervention period. 
• 
Participants who miss a scheduled meeting are contacted by telephone by study staff to 
encourage continued participation and to evaluate and overcome barriers to 
participation. 

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42 
• 
Home visits for intervention sessions will be considered on a case-by-case basis by the 
study staff and interventionist when needed because of participant inability to travel to 
clinic-based study visits. 
• 
Participants are informed that they are allowed to keep the hearing aids and other 
hearing technologies for free if they complete all study visits. 
• 
At the completion of the study, participants in the hearing intervention may also choose 
to receive the successful aging intervention. 
 
 
Strategies for Promoting Adherence in the Successful Aging Intervention 
 
Strategies to promote adherence in the Successful Aging Intervention include: 
• 
Expectations of potential benefits of the intervention are structured in order to ensure 
that participants’ expectations are reasonable and realistic. 
• 
Individual assessment and instruction. 
• 
Participants can bring a friend or family member with them to intervention visits 
(analogous to the communication partner for participants randomized to the hearing 
intervention). 
• 
Establishes concrete and reasonable goals related to attending the Successful Aging 
sessions and participating in that intervention throughout the intervention period. 
• 
Easy-to-read written materials are distributed at each visit to prompt regular and 
appropriate participation.  
• 
Participants are encouraged to track behavior changes related to topics covered as part 
of the program.  
• 
Participants who miss a scheduled meeting are contacted by telephone by study staff to 
encourage continued participation and to evaluate and overcome barriers to 
participation.  
• 
Home visits for intervention sessions will be considered on a case-by-case basis by the 
study staff and interventionist when needed because of participant inability to travel to 
clinic-based study visits. 
• 
At the completion of the study, participants in the successful aging intervention may also 
choose to be fitted for hearing aids and provided hearing rehabilitation resource 
materials if they are interested.  
 
Strategies to Minimize Bias from Unblinded Study Participants and Staff 
 
Neither study participants nor study technicians collecting outcome data can feasibly be blinded 
to randomization status. We will minimize bias from unblinded study participants and staff 
through the following strategies based on recommendations from Boutron et al.23 for blinding in 
non-pharmacological trials: 
  
• 
Use of an attention control intervention Participants are randomized to one of two 
interventions – hearing rehabilitative intervention vs. an established successful aging 
intervention that serves as an attention control. This successful aging intervention is 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
43 
based on the 10 Keys™ to Healthy Aging program developed by the Center for Aging 
and Population Health Prevention Research Center at the University of Pittsburgh1 and 
which was successfully implemented as the attention control intervention in the 
unblinded Lifestyle Interventions and Independence for Elders (LIFE) study.2 The use of 
an attention control intervention that is perceived as having value to study participants 
can minimize participant dissatisfaction with not obtaining the hearing loss intervention. 
In the ACHIEVE-Pilot study, study staff reported strong participant enthusiasm for the 
successful aging intervention. The study overall will communicate that it has two 
interventions aimed at successful aging. They are very different and expected to have 
different benefits which are unknown. The goal is to identify which intervention has which 
benefits including cognition and other measures of aging. 
• 
Blinding of study participants to study hypothesis Informational material and the consent 
provided to study participants will emphasize that the ACHIEVE study is comparing two 
established interventions in which it is not known whether either intervention could affect 
cognitive decline. Blinding of study participants to the explicit hypothesis that the hearing 
intervention reduces cognitive decline can help promote acceptance and adherence to 
both study interventions.    
• 
Standardized protocols for training of data collectors & assessment of study outcomes 
Strict and standardized protocols for assessment of neurocognitive functioning will be 
implemented to minimize bias during data collection. Protocols (see Manual of 
Procedures) for both training/certification of psychometrists and quality 
assurance/control have been well-established and tested in both ARIC-NCS and the 
ACHIEVE-Pilot study. These protocols incorporate regular recordings/observations of 
data collection sessions for feedback/quality control and centralized training of all 
psychometrists on a standardized protocol for neurocognitive test administration. 
Importantly, we will also utilize a supplementary standardized protocol incorporating an 
assessment of spoken language understanding to ensure that speech understanding is 
not confounding neurocognitive testing or other data assessments (section 7.2.2). 
Dementia adjudication procedures based on consensus conference review of study data 
will be blinded to randomization status. These procedures will help minimize potential 
bias from unblinded data collection staff.  
• 
Data collectors & study coordinators will not have access to cognitive testing results from 
prior study visits Cognitive test data from prior study visits will not be available to data 
collectors and study coordinators in order to avoid unintentional and possibly 
unconscious bias by study staff during data collection. All data collection staff are distinct 
from staff who are involved with intervention administration. In addition, the primary and 
key secondary outcomes based on cognitive testing factor scores described in section 
12.3 will not be made available to the site study staff. 
  
Of note, the ACHIEVE Steering Committee did consider at length alternate study designs to 
allow for blinding of study technicians including having all participants use a body-worn sound 
amplifier at all visits, having all participants use no hearing devices at any visits (to mimic the 
state at baseline testing), having all participants wear “covers” over their ears, or having 
participants randomized to successful aging wear “sham” hearing aids during testing. The 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
44 
former two approaches would adversely affect neurocognitive testing (in which prevailing 
neuropsychometric standards stipulate that participants use whichever sensory aids they use on 
a regular daily basis). All four approaches were found to be pragmatically infeasible through 
discussion with field site staff and potential study participants. 
 
 
11 Safety monitoring 
11.1 Data and safety monitoring board 
An independent Data and Safety Monitoring Board (DSMB) has been constituted in 
collaboration with the NIA. The DSMB will provide oversight to ensure that the trial accrues at a 
sufficient rate and that the safety and privacy of all study participants are maintained. DSMB 
members are clinicians/investigators with expertise in clinical trials, neurology, dementia, 
biostatistics, audiology, and otolaryngology. A DSMB charter which was approved by the DSMB 
and the NIA specifies guidelines for DSMB conduct and early stopping rules for safety and 
futility. We anticipate meetings of the DSMB every 6 months after the first year, always focused 
on participant safety, but initially focusing on recruitment and follow-up. 
 
There will be no interim analysis for efficacy. We do not expect to see an efficacy signal of 
sufficient magnitude to stop the trial with periods of follow-up shorter than 3 years. Combined 
with the comparatively shorter recruitment period, there is minimal expected benefit from an 
interim efficacy analysis. A formal interim analysis to evaluate for futility and sample-size re-
estimation will be performed after 66% of subjects have completed the study, as described 
below in section 12.4. 
11.2 Adverse events 
Study participation and exposure to the hearing aid intervention is expected to have a low risk of 
adverse events for the participant. At the same time, the age of the participants may naturally 
lead to numerous deleterious health outcomes. In order to efficiently collect safety information 
that is relevant to study participation, interventions, and procedures, detailed information 
concerning a pre-specified set of adverse events and serious adverse events will be collected 
and evaluated throughout the conduct of the trial.  
An adverse event (AE) is an untoward medical occurrence, whether or not considered study-
related, which occurs during the conduct of a clinical trial 
A serious AE (SAE) is any AE that results in any of the following outcomes: 
• Death 
• Life-threatening  
• Inpatient hospitalization or prolongation of existing hospitalization  
• Results in persistent or significant disability or incapacity 
• A major congenital anomaly or birth defect  
• Important medical event that may not result in one of the above outcomes, but may 
jeopardize the health of the study participant or require medical or surgical intervention to 
prevent one of the outcomes listed above.  

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
45 
For this study, only the following adverse events and serious adverse events will be 
recorded and reported: 
Adverse Events 
Serious Adverse Events 
• 
Otitis externa 
• 
Death from any cause 
• 
Cerumen impaction or ear foreign body 
requiring removal by a physician 
 
An adverse event of otitis externa is defined as inflammation or infection of the ear canal 
resulting in pain, swelling, irritation, itching, or other related symptoms as diagnosed by the 
study audiologist or a physician. Adverse event severity is defined as: 
• 
Mild if the symptoms are self-limited and resolve with interventions such as transiently 
limiting hearing aid use and/or the use of over-the-counter pharmacological therapies 
such as hydrocortisone cream or swimmer’s ear drops.  
• 
Moderate if the symptoms require evaluation and management by a physician and the 
use of topical prescription pharmacological therapies such as antibiotic ear drops.  
• 
Severe if the symptoms require evaluation and management by a physician and the use 
of oral or parenteral antibiotics.  
 
An adverse event of a cerumen impaction or ear foreign body requiring removal by a physician 
is defined as a cerumen impaction and/or ear foreign body that cannot be routinely managed by 
the study audiologist and requires evaluation and management by a physician (typically an 
otolaryngologist). Adverse event severity is defined as:  
• 
Mild if the cerumen impaction or foreign body is resolved without further need for 
therapy besides over-the-counter pharmacological therapies such as cerumenlytic 
drops. 
• 
Moderate if there is an associated otitis externa requiring the use of topical prescription 
pharmacological therapies such as antibiotic ear drops.  
• 
Severe if the cerumen impaction or ear foreign body results in a perforation of the 
tympanic membrane or an associated otitis externa requiring the use of oral or 
parenteral antibiotics.  
 
AEs or SAEs will be defined as unexpected or expected based on the judgement of the field 
site PI in consultation with the study audiologist and/or study PI Lin (who is a board-certified 
otolaryngologist) based on the following definitions:  
• 
Unexpected – nature, severity, or frequency of the event is not consistent with 
information about the condition under study or intervention in the protocol and consent 
form 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
46 
• 
Expected – event is known to be associated with the intervention or condition under 
study.   
 
Study-relatedness of AEs or SAEs will be based on the judgement of the field site PI in 
consultation with the study audiologist and/or study PI Lin based on the following guidelines:  
• 
Definitely Related:  The adverse event is clearly related to the investigational 
intervention – i.e., an event that follows a reasonable temporal sequence from 
administration of the study intervention, follows a known or expected response pattern to 
the suspected intervention, that is confirmed by improvement on stopping and 
reappearance of the event on repeated exposure and that could not be reasonably 
explained by the known characteristics of the subject’s clinical state. 
• 
Possibly Related:  An adverse event that follows a reasonable temporal sequence from 
administration of the study intervention, that follows a known or expected response 
pattern to the suspected intervention, but that could readily have been produced by a 
number of other factors. 
• 
Not Related:  The adverse event is clearly not related to the investigational 
agent/procedure - i.e., another cause of the event is most plausible; and/or a clinically 
plausible temporal sequence is inconsistent with the onset of the event and the study 
intervention and/or a causal relationship is considered biologically implausible.  
 
Unanticipated Problems 
 
An unanticipated problem is defined as an incident, experience, or outcome that meets all of the 
following criteria: 
• 
Unexpected – in terms of nature, severity, or frequency given the procedures and 
interventions used in the ACHIEVE study as described in the protocol and informed 
consent given the characteristics of the study population 
• 
Possibly or definitely related to the participation in the ACHIEVE study 
• 
Suggests that the research placed the participant or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously known 
or recognized 
 
Some but not all adverse events may qualify as unanticipated problems.  
 
The DSMB will review all recorded treatment-emergent adverse events and all serious adverse 
events (SAEs) from this pre-specified list and will provide a report to the Steering Committee 
and to the local IRBs. An SAE that is unexpected and possibly or definitely related to study 
participation or study intervention will be reported within 48 hours by the sites to the local 
IRB and the PI to the NIA and DSMB.  
Adverse events and serious adverse events will be recorded on the electronic Adverse Events 
Form per study instructions. Additionally, for unexpected and possibly or definitely related 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
47 
serious adverse events only, sites will record a narrative description of the serious adverse 
event, including any relevant lab test results and dates.  
All completed AE forms will be forwarded promptly to the Coordinating Center where they will be 
reviewed for completeness by the Coordinating Center staff and the ACHIEVE Principal 
Investigator (Lin). In particular, the Principal Investigator will assure that documentation of each 
event is adequate to permit accurate inferences regarding causation (e.g., temporal 
associations, onset, course, response to patient or physician intervention, alternative etiologies) 
and severity. 
Full details of procedures for reporting adverse events can be found in the MOP. 
 
12 Statistical considerations 
12.1 Sample size 
Aim 1: Comparison of hearing rehabilitative intervention versus successful aging control 
intervention for 3-year cognitive decline 
Our sample size calculation is based on the primary outcome, the change in the Global 
Cognitive Function Factor Score from baseline to year 3. Estimates are based on the rate of 
change in the global cognitive function factor score from the first third of participants in the 
ongoing ARIC Visit 6 study (2016 to 2017) in addition to data from other representative studies 
with similar cohort characteristics as ARIC/ACHIEVE (i.e., ACTIVE and HealthABC). We also 
take into account assumptions regarding the rate of loss to follow-up as well as the rate of 
cross-over, where participants in the successful aging control group begin to wear hearing aids 
and participants in the hearing intervention group stop wearing the devices. 
We based these calculations on a t-test comparing groups on change from baseline at 3 years 
to align with the primary analysis (a mixed effects model treating time as categorical) and aimed 
to achieve 90% power using a 2-sided test with a p=0.05 significance level. We conservatively 
chose parameter estimates that fell within the mid-range of observed values from these studies.  
Parameter assumptions include: 
• 
Change in global cognitive function factor score in the control group per year:  
Estimated at -0.08 standard deviations (SD)/year (corresponding to -0.24 SD in 3 years) 
  
• 
Standard deviation of change in global cognitive function factor score per year:  
Estimated at 0.09 (corresponding to 0.27 at 3 years)  
• 
Drop-in/Drop-out: Estimated as a net total of 15% (drop-in + drop-out) for the 3-year 
study. This value is conservative. We assumed immediate drop-in/drop-out rather than 
later drop-in/drop-out (i.e., 1-2 years into the study) which would have less impact on 
reducing the observed effect size. We will continue to optimize the design to keep both 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
48 
drop-in and drop-out rates low (e.g., rigorous training for active group vs. energized 
successful aging group promised free hearing aids at trial completion). Among 13 
participants in the ACHIEVE-Pilot study who were randomized to the hearing 
intervention and have since been followed to 1 year, we did not observe any drop-out 
(discontinuation of hearing aid use) at 1 year (12 participants reported > 8 hours of 
hearing aid use/day and 1 participant reported 4-8 hours use/day). Similarly, drop-in 
rates will likely be minimized because all participants in the successful aging group are 
informed that they will receive free hearing intervention after 3 years of follow-up (out-of-
pocket costs for hearing aids are otherwise currently ~$4700 and are rarely covered by 
insurance). Rates of uptake of hearing aid use remain low in the community. In the 
HealthABC study among individuals with hearing loss in the inclusion range for the 
ACHIEVE study, rates of hearing aid uptake were ~3-4% per year.  
• 
Missing data/withdrawal from competing events (e.g., mortality not associated with 
dementia): Estimated at 10%/year (corresponding to 27% in 3 years)  
Based on these parameters and with 850 total individuals randomized, we will have 90% power 
to detect a 35% difference in annual cognitive decline between the hearing intervention vs 
successful aging intervention at 3 years follow-up.  
Aim 2: For the secondary outcome of incident cognitive impairment, a dataset was constructed 
of participants in the ARIC cohort who had comparable characteristics to the individuals enrolled 
in ACHIEVE, did not exhibit signs of cognitive impairment at the baseline, and who were 
monitored over a period of 5 to 8 years. The observed rate was 50 cases of incident cognitive 
impairment per 1000 person-years. Assuming a 30% reduction in the hearing intervention 
condition and a 25% loss of person-time due to attrition, the planned analysis would have 80% 
power to detect a hazard ratio of 0.54 when using a 2-sided test and p < 0.05. 
12.2 Analytic approach 
Analyses will follow the intention-to-treat (ITT) principle in which subjects will be analyzed in the 
group to which they were randomized, regardless of whether or not they received the assigned 
intervention. Primary analyses will be based on the ITT population, which includes all 
randomized subjects. In addition, a secondary analysis of the primary outcome will be 
completed for the per-protocol (PP) population, defined as a subset of the ITT population who 
completed the 8-10 week intervention period, had no hearing aid intervention drop-in for the 
control group, and had no major protocol deviations. Major protocol deviations include violations 
in inclusion and exclusion criteria at enrollment and poor compliance with hearing aids for the 
hearing aid intervention group, defined as subjects who discontinue hearing aid use. All major 
protocol deviations will be identified in a blinded fashion prior to database lock. Complier 
average causal effect analysis will also be conducted to mitigate bias present in per protocol 
analyses. 
Consistent with best practices in clinical trials, we will assess the comparability of the 
randomized groups with respect to known baseline confounders such as hearing loss (pure-tone 
average in the better hearing ear <40 dB vs ≥40 dB), recruitment source (ARIC vs de novo), 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
49 
field center, age, sex, education, and the presence of APOE ε4 alleles.24  If, despite 
randomization, there is an imbalance between the treatment conditions, we will adjust for 
relevant confounders as well as explore the use of a precise, locally efficient, augmented, 
simple estimator25 which may offer greater precision. 
 
Primary Outcome  
The primary outcome is cognitive decline, as measured by the change in a global cognitive 
function factor score. The factor score is derived from a confirmatory factor analysis model that 
identifies common covariation among all cognitive tests administered in-person. Factor scores 
are generated for each participant at each in-person assessment using a measure 
harmonization and item banking approach.26, 27 Factor loadings and latent means for each 
neurocognitive test are estimated using data from the ACHIEVE baseline. 
 
Primary Analysis  
Groups will be compared for the primary outcome using mixed effects models that account for 
the correlation among repeated measures as well as the correlation between spouses or 
cohabitating partners. If a linear trend appears reasonable, we will fit a model with a linear 
slope. If a nonlinear trend is observed, the model will be adapted to include time splines.28 
Continuous time in years from the baseline will be the time scale. An interaction term between 
treatment assignment and time will be used to test if rates of cognitive change differ by 
treatment assignment. Model fit will be assessed with residual plots and other statistics (Akaike 
Information Criterion, Bayesian Information Criterion, etc.). The primary analysis may include 
adjustments for the baseline hearing loss, ARIC vs de novo status, field center, age, sex, 
education, and APOE ε4 alleles. 
Missing cognitive factor scores among ACHIEVE participants will be generated utilizing multiple 
imputation by chained equations.29 The number of imputations needed to generate valid 
parameter estimates will be determined by a two-stage analysis.30 The imputation model will 
include (1) in-person cognitive factor scores, (2) MMSE and Six-item Screener scores, (3) 
adjudicated incident MCI or dementia, (4) race, (5) time variables indicating when a participant 
with missing data might have completed an assessment based on time from randomization to 
missed visit, and (6) all previously listed covariates. Interactions between variables in the 
imputation model will be tested and added as necessary. The imputation will be conducted in 
stages so that concurrent and past measurements, but not future measurements, inform the 
imputed values. The validity of the imputation model will be assessed by comparing observed 
values to imputed values among a 20% sample selected at random and a 20% sample selected 
based on the probability of missingness estimated from a logistic regression model. 
The primary analysis will focus on cognitive factor scores imputed prior to death. An analysis 
comparing pre- and post-death cognitive factor scores will be performed using values generated 
from an imputation model in which death is included as an auxiliary variable. A similar 
procedure will be used to contrast pre- and post-dementia cognitive factor scores.  

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50 
 
Sensitivity Analyses of the Primary Outcome 
Additional analyses of the primary outcome may include, but are not limited to: 
(a) An analysis of global cognitive function in which data from in-person cognitive 
evaluations will be stratified by condition before a factor score is computed for each 
participant. The factor scores generated will be standardized using the condition-specific 
baseline mean and SD. 
(b) An analysis of a co-calibrated31,32 global cognitive function factor score in which the ten 
tests administered in-person and the six tests administered over the phone will be 
included in the confirmatory factor analysis model. Modeling constraints will be applied 
to scale the co-calibrated factor score to the same metric as the in-person factor score 
utilized in the primary analysis.33 Mode of data collection (in-person, phone) will be 
included in the analytic model as a covariate. 
(c) Use of full-information maximum likelihood to account for missing data. Parameter 
estimates from these analyses will be compared to estimates from multiple imputation 
analyses to gauge the impact of including auxiliary variables in the imputation model. 
(d) Control-based multiple imputation, in which missing values of the primary outcome for 
the hearing aid condition without a dementia diagnosis are imputed based on the 
successful aging control intervention condition. This analysis will investigate the strength 
of the primary analysis results to the missing at random assumption. 
(e) Analysis of cognitive decline based on a categorized version of time (visits) rather than 
continuous time in years. 
(f) A replication of the primary analyses stratified by subgroups of ARIC vs de novo 
participants. Interaction between intervention condition and recruitment group will be 
tested in additional models relative to p < 0.10. 
(g) Exploration of the impact on the primary analysis by further adjustment for additional 
explanatory variables, as mentioned above. 
 
Exploratory Analyses of the Primary Outcome  
a) Differential practice effects by recruitment source The study recruited participants 
from ARIC and from a community sample. ARIC participants have had prior exposure to 
testing while non-ARIC participants have not. To address this potential limitation, we will 
use a mixed effects modeling framework to examine practice effects using an indicator 
for the first visit in each condition, allowing the practice effect parameter to vary by 
recruitment source and keeping the estimated intervention effect constant. We will test 
the fit of that model to one where the intervention effect differs by condition to evaluate 
whether differential practice effects by recruitment source affects the intervention 
condition difference. This is a test of effect modification.  

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
51 
b) Does intervention alter the trajectory of cognitive decline In the subset of ARIC 
participants, we will model prior cognitive change (before the baseline ACHIEVE visit) as 
well as prospective change through study end (2021-22) using linear spline models, to 
determine if the rate of change of cognitive decline during ACHIEVE in each condition is 
different than the rate of change in the preceding years in ARIC visit 5 and 6. We will 
also test the interaction hypothesis that the hearing intervention deceleration in decline is 
larger than that in the successful aging intervention condition. The power for analyses in 
the ARIC subgroup will be lower than optimal since the proportion of ACHIEVE 
participants recruited from ARIC was smaller than originally anticipated. 
c) Subgroup analyses by demographics Given the lower prevalence of hearing loss in 
women compared to men and blacks compared to other races, an exploratory analysis 
will be conducted stratifying by sex, race, and education. We will also conduct analyses 
stratifying by level of hearing loss and level of baseline global cognitive function factor 
score. Interaction between intervention condition and subgroups will be tested in 
additional models relative to p < 0.10.  
d) Subgroup analyses by AD risk factors We will investigate a further refinement of the 
primary analysis with subgroup analysis for known AD risk factors, including but not 
limited to ≥1 APOE ε4 allele, as well as diabetes or hypertension. A subset of ARIC 
participants will be defined as more likely to be at high risk of AD based on reduced 
temporal lobe volume meta ROI33 by structural MRI and no small vessel disease (ARIC 
Visit 5, 2011-13).  
e) Exclusion of tests with only auditory stimuli Among the full study cohort, we will 
derive a revised global cognitive function factor score excluding tests with only auditory 
stimuli (Logical Memory, Digits Backward). We will use model constraints in a latent 
variable modeling framework to scale these revised factor scores to be on the same 
metric as the factor scores in the primary analysis.34 
f) Mediation by social function Investigate the extent to which the cognitive 
improvements are mediated by improvements in social function using causal mediation 
methods.35 
 
Secondary Outcomes 
An important secondary outcome is time until a composite of (1) adjudicated dementia 
determined from in-person or phone-based evaluations, (2) adjudicated MCI26 determined from 
in-person evaluations (3) a 3-point drop in the 30-item MMSE administered in-person, or (4) a 3-
point drop in a factor score derived from the 10-item MMSE orientation subscale and 11-item 
Blessed scale administered over the phone and rescaled to be equivalent to the 30-item MMSE. 
Intervention conditions will be compared for the time until the composite outcome utilizing a 
discrete-time, cause-specific proportional-hazards model with a complimentary log-log link. The 
same baseline covariates specified for the mixed effects model will be integrated into the 
proportional-hazards model. Time on study will be the time scale. As a sensitivity analysis, we 
will examine variations of the composite outcome that include (1) adjudicated MCI from phone-

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
52 
based evaluations and (2) unadjudicated MCI diagnoses identified algorithmically. In exploratory 
analyses, we will analyze time until (1) adjudicated dementia or MCI diagnosis and (2) decline in 
MMSE and Blessed scores as separate events.  
Three additional secondary outcomes that will be examined include decline in the cognitive 
domain factor scores for memory, executive function, and language9 derived from in-person 
assessments. Intervention conditions will be compared using the same statistical methods 
described above for the primary outcome. Results from the analysis of the four secondary 
outcomes will be included in the primary outcome manuscript. 
Adjustment for Multiple Comparisons 
Statistical significance for the primary outcome will be defined as p <0.05. Secondary outcomes 
will be evaluated for statistical significance with a Hochberg modification to the Bonferroni 
adjustment, in which the p-values of the five outcomes will be ordered. The largest p-value will 
be compared relative to p <0.05, and if met, all parameters will be considered significant. If not, 
then the second largest p-value will be assessed relative to p <0.05/2 = 0.025, and if met, then it 
and all other parameters will be considered significant, and so on for the third p-value compared 
to 0.05/3=0.017, the fourth compared to 0.05/4 = 0.012, and the fifth compared to 0.05/5 = 0.01.  
Additional Pre-Specified Outcomes 
Additional measures include measures of social and physical function, physical activity, and 
HRQL. Analyses of all other outcomes are considered exploratory in nature and will not be 
viewed as providing confirmatory tests of hypotheses. There will be no adjustment for multiple 
comparisons of the exploratory pre-specified outcomes, and p-values will be provided for 
descriptive purposes only. 
Outcomes will be modeled continuously (outcomes transformed to account for non-normality if 
necessary) or categorized according to clinically-relevant cut-points.37 Intervention groups will 
be compared using the same approach adopted for the primary analysis.37 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
53 
 
12.3 Global cognitive function factor score 
Properties and advantages 
The global cognitive function factor score uses all available cognitive test data, has interval-level 
properties,38 is internally consistent using ARIC-NCS data (Cronbach’s alpha=0.87), has 
minimal floor or ceiling effects,39 and demonstrates reliable measurement precision over a broad 
range of cognitive ability. We have previously demonstrated criterion validity and established 
cut-points for clinically relevant impairment of the general cognitive performance factor score.39 
We have since extended the harmonization to 26 studies with over 60,000 people, most of 
which have longitudinal data. Using simulation, we verified the cognitive metric is the same 
across dataset.39  We compared precision of our approach with other approaches to combining 
data using external data: underscoring enhanced precision in a sample of 10,875 persons in 9 
datasets, our approach required the smallest sample size to detect cognitive decline with 80% 
power (N=232) compared to using only the MMSE (N=277) or summarizing available tests into 
a z-score (N=291).34,40 We further validated the approach against change in hippocampal 
volume and overall cortical thickness.34 The approach is consistent with other harmonization 
techniques and has been used in several other published studies33, 39-44 including 
demonstrations that the factors have the same meaning across datasets with different cognitive 
tests.33, 39-43, 45-49 
12.4 Assumptions analysis 
An assumptions analysis took place in June 2019, prior to the closure of the initial recruitment 
period. The goal of the analysis was to evaluate a subset of the assumptions described above 
and assess the value of a possible increase in the sample size. Since ACHIEVE was not going 
to be stopped early for efficacy or futility, regardless of the interim results, and the interim 
analysis only investigated assumptions around attrition and drop-in/drop-out rates, not 
outcomes, the interim analysis did not lead to increased type I error rates. Moreover, it was 
important to determine the extra required sample size, if any, as soon as possible in order to 
promptly begin the second stage of recruitment and expand the sample while there were still 
active participants from the initial stage.  
 
Both the attrition rate and the drop-in/drop-out rate were examined based on 1 year follow-up 
data from approximately 200 participants. The data suggested that the original assumptions 
made in the sample size calculations were reasonable. However, there was potential variability 
in the estimates since partial data were used in the analysis. Consequently, the DSMB 
recommended increasing the sample size up to 1000 participants. The final sample size is 977 
participants. This increased sample provided additional power for all tests, including greater 
than 90% power to detect a difference in cognitive decline after accounting for the estimated 
attrition and drop-in/drop-out rate as well as 80% power to detect a hazard ratio of 0.60 in the 
proportional-hazards analysis of incident cognitive impairment 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
54 
13 Data management 
Trained data management and study management staff at the UNC CSCC will be responsible 
for coordinating data management. The Data Coordinating Center (DCC) will develop a 
customized web-based data management system for the ACHIEVE trial, using the Carolina 
Data Acquisition and Reporting Tool (CDART), a state-of-the-art data management system that 
is currently used for ARIC-NCS. A complete description all data management procedures can 
be found in the MOP. 
Data collection 
The CSCC will lead the translation of the protocol data collection specifications into a 
consolidated set of clear, unambiguous data collection forms (electronic case report forms, 
eCRFs). Each eCRF will have a corresponding paper form to be used by sites in cases where 
data cannot be entered at the time of collection. Most of the CRFs have already been developed 
as part of ACHIEVE-P study and ARIC-NCS. Developing CRFs can uncover discrepancies 
within the protocol; thus, forms, the protocol, and manual of procedures will be finalized in 
unison during study startup.  
Randomization and unblinding  
Randomization, stratified by ARIC study status, field center, and hearing impairment level is 
completed within CDART. Although ACHIEVE hearing aid intervention is by nature un-masked, 
in order to minimize bias based on review of accumulating data by the project team, the 
ACHIEVE PI, co-investigators and key project staff except data coordinating center staff and 
one unblinded statistician will remain blinded to accumulating data.  
Data reporting & extraction 
CDART reports are run from the database in real-time and can run across multiple research 
sites to provide participant feedback, assist in participant visit scheduling, monitoring data 
quality and protocol adherence, track study enrollment, and identify medical alert values (e.g., 
blood pressure, depression scores, etc.).  
Data security and confidentiality 
CDART uses a flexible, secure authentication system requiring a username and password. In 
accordance with HIPAA, all individually identifiable information is encrypted and decrypted for 
local on-screen display at clinical centers for their own participants. 
 
14 Data handling and record keeping 
Confidentiality 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Those 
regulations require a signed subject authorization informing the subject of the following:  

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
55 
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of their PHI 
In the event that a subject revokes authorization to collect or use PHI, the investigators, by 
regulation, retain the ability to use all information collected prior to the revocation of subject 
authorization. For subjects that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (i.e. that the subject is alive) 
at the end of their scheduled study period. 
 
Source Documents 
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source 
data are contained in source documents. Examples of these original documents, and data 
records include: hospital records, clinical and office charts, laboratory notes, memoranda, 
subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified after verification as being accurate and 
complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject 
files, and records kept at the pharmacy, at the laboratories, and at medico-technical 
departments involved in the clinical trial. 
 
Electronic Case Report Forms 
The study electronic case report form (CRF) will be the primary data collection instrument for 
the study. All data requested on the CRF will be recorded and all missing data will be explained. 
For ease of data collection, paper forms can be used by the site, in which case the paper form 
becomes part of the source documents.  
 
Records Retention 
Co-PIs and field center PIs will retain study essential documents and specimens for up to 10 
years following study completion. 
 
15 Quality assurance and quality control 
Established quality assurance procedures used in ARIC-NCS will be followed. Full details can 
be found in MOP. 
15.1 Fidelity of hearing intervention 
To ensure fidelity of the hearing intervention, field site training of study staff, including study 
audiologist and delegated hearing intervention study staff, as well as intervention delivery, 
receipt, and enactment will be monitored by the USF co-investigator team - Drs. Chisolm, 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
56 
Eddins, Sanchez, and Arnold. Fidelity assurance begins with centralized training conducted by 
the USF co-investigator team. Should there be personnel changes during the course of the 
study, the new field site audiologist or study staff will be trained as-needed either during a site 
visit or remotely, depending on individual field site needs. Training will consist of informational 
and hands-on learning activities and will be assessed via skill observation with mock 
participants as well as a written examination. During the first quarter of participant testing, 
weekly phone calls will take place between each site and the USF team to address site-specific 
issues and monitor overall fidelity. During the second and third quarters, phone calls will take 
place biweekly, and during the fourth quarter and onward, phone calls will take place monthly. In 
addition, a random sample of paper data forms will be selected for chart review at regular 
intervals throughout the trial. Chart reviews will be conducted to verify accurate data entry from 
the paper source to CDART. Site visits and remote monitoring will also be conducted, 
determined based on sites’ needs, for additional support or as supplemental training for new 
study audiologists. Study audiologists will be informed at centralized training that a sample of 
sessions will be video or audio recorded, and 10% will be chosen at random for remote review 
with feedback provided to the study audiologist by the USF team. Trackable documentation will 
be kept for accountability including certificates of study staff and study audiologist training and 
reports after site visits and phone calls.  
15.2 Fidelity of successful aging intervention 
To ensure fidelity of the Successful Aging intervention, observations of health educators will be 
conducted via a site visit conducted by Dr. Glynn. Health educators will be informed at 
centralized training that a sample of sessions will be also be audio taped; ten percent of the 
sessions will be chosen at random and feedback provided to the health educator by Dr. Glynn. 
Further, Dr. Glynn will lead monthly Successful Aging subcommittee calls to ensure the control 
program is being conducted in the manner outlined in the manual of procedures as well as to 
troubleshoot any participant-related issues. 
15.3 Quality assurance of data entry 
All staff involved with data collection will be required to have appropriate electronic data 
management system training. The training course includes a primer on using CDART for data 
collection and data reporting. In addition to training and providing reference documentation, the 
DCC may be contacted by telephone with questions about using CDART. CDART has 
embedded quality control measures in the application. These include reports on missing data 
fields and range-checks on each data field where applicable. Additional reports may be 
developed to check cross-form consistencies. These reports facilitate timely identification and 
resolution of problems in data collection and processing. The CDART User’s Manual is found in 
MOP. 
 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
57 
16 Study monitoring, auditing, and inspecting 
Study Monitoring Plan 
The Co-PIs and field center PIs will monitor the study to ensure quality and integrity of data 
collected. They will review study files, regulatory documents, consent forms and allocate 
adequate time for other study monitoring activities. Field centers will be monitored periodically 
by representatives from the data coordinating center. The Co-PIs and field center PIs will also 
ensure that the monitor or other compliance or quality assurance reviewer is given access to all 
the above noted study-related documents and study related facilities and has adequate space to 
conduct the monitoring visit. 
 
Auditing and Inspecting 
Co-PIs and field center PIs will permit study-related monitoring, audits, and inspections by the 
IRB, University compliance and quality assurance groups of all study related documents (e.g., 
source documents, regulatory documents, data collection instruments, study data etc.). PIs will 
ensure the capability for inspections of applicable study-related facilities.  
 
Ethical Considerations 
This study is to be conducted according to US and international standards of Good Clinical 
Practice (FDA Title 21 part 312 and International Conference on Harmonization guidelines), 
applicable government regulations and Institutional research policies and procedures. 
This protocol and any amendments will be submitted to a properly constituted Institutional 
Review Board (IRB), in agreement with local legal prescriptions, for formal approval of the study 
conduct. The decision of the IRB concerning the conduct of the study will be made in writing to 
the investigator and a copy of this decision will be provided to the sponsor before 
commencement of this study.  
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study. This consent form will be submitted with the protocol for review and approval by the IRB 
for the study. The formal consent of a participant, using the IRB-approved consent form, will be 
obtained before that participant undergoes any study procedure. The participant will sign the 
consent form, and the investigator-designated research professional obtaining the consents. 
 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
58 
17 Timeline 
Project YR 
1 
2 
3 
4 
5 
Quarter 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 
Finalize Protocol 
x   
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Finalize MOP/forms 
x   
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Finalize Analytic Plan x   
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Establish DSMB 
x x   
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Training 
  
x   
  
  
x   
  
  
x   
  
  
x   
  
  
x   
  
Recruitment 
  
  
x x x x x x x x   
  
  
  
  
  
  
  
  
  
Intervention 
  
  
x x x x x x x x   
  
  
  
  
  
  
  
  
  
Follow-up 
  
  
  
x x x x x x x x x x x x x x x x x 
Primary Analysis 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
x 
Publication/Closeout 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
x 
*Interim analysis for sample size re-estimation will be done after 66% of study completion 
(expected during year 5). 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
59 
18 Organization of the study 
Organizational structure for year one of the ACHIEVE study is shown in Figure 1. In brief, the 
Steering Committee will oversee all study activities and be chaired by the two Co-PI’s (Lin, 
Coresh) and be comprised of all committee chairs and center leads. The ACHIEVE working 
group committees (Chairs) include Operations (Lin/Ring), Design and Analysis (Couper/Coresh) 
Neurocognitive & Dementia Adjudication (Mosley/Albert), Secondary Outcomes/Ancillary 
Studies (Schrack/Coresh), Intervention Fidelity & Quality (Chisolm/Glynn), Publications 
(Deal/Coresh), DCC (Couper/Burgard). Any updates to the organizational structure will be noted 
in the MOP. 
 
Figure 1. Organizational structure for year one of the ACHIEVE study 
18.1 Key roles of committees 
• 
Steering Committee 
o The steering committee will meet regularly to manage the study. 
• 
Operations Committee 
o Monitoring recruitment/retention 
o Staff training 
o Development of MOP, CDART, data forms 
o Coordination with ARIC-NCS 
o Data management implementation 
o Subcommittee: Field Site Research Coordinators 
o Subcommittee: Recruitment 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
60 
• 
Design and Analysis Committee 
o Finalize analytic plan and protocol for ACHIEVE trial 
o Develop DSMB charter and DSMP for ACHIEVE in partnership with NIA 
• 
Neurocognitive/ Dementia Adjudication Committee 
o Oversight of neurocognitive battery administration 
o MCI/dementia adjudication 
o QA/QI of neurocognitive battery administration and collected data 
• 
Secondary Outcomes and Ancillary Studies Committee 
o Oversight of secondary outcome battery 
o Consideration of ancillary studies 
o QA/QI of secondary battery administration and collected data 
• 
Intervention Fidelity and Quality Committee 
o Oversight of fidelity of study interventions 
o Subcommittee: Hearing intervention 
o Subcommittee: Successful aging intervention 
• 
Publications Committee 
o Review of all planned conference abstracts and manuscripts 
• 
Data coordinating center 
o Management of data. 
o Organization of centralized training. 
 
19 Changes as a result of COVID-19 
The impact of the COVID-19 global pandemic has necessitated changes to the ACHIEVE 
protocol. This is to protect the ACHIEVE participants, ACHIEVE study staff, and the wider 
community from the risk of infection from COVID-19 and to adhere to institutional, state, and 
federal guidelines in response to the pandemic. This section details the changes as a result of 
COVID-19. 
 
19.1 Remote visits 
In mid-March 2020, all field sites suspended in-person study visits. Until in-person data 
collection is deemed safe to resume with appropriate protections in place, semi-annual and 
annual visits, including neurocognitive assessment, intervention booster sessions, and 
secondary outcome data collection, will occur via telephone or HIPAA-compliant video call (e.g., 
Zoom) according to the schedule shown in the table below. Specific guidance for these 
telephone contacts is provided in a COVID-19 MOP Appendix.  For ACHIEVE participants due 
for their final Year 3 study visit while field site clinics were still closed, their final study visit will 
be a split visit that will comprise both a phone-based component on schedule and a delayed in-
person component that will be conducted once field site clinics reopen.  At these in-person 
visits, final data elements will be collected, and participants will be able to receive the other 
study intervention, as promised at the beginning of the trial. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
61 
Table 4. Schedule of Evaluations for Remote Data Collection 
Assessment 
Follow-Up Visits 
Visit 6  Visit 7  Visit 8  Visit 9 Visit 10 Visit 11 
(6mo) (12mo) (18mo) (24mo) (30mo) (36mo) 
 
Yr1 
 
Yr2 
 
Yr3 
Covariates 
Health History Form 
X1 
X 
X1 
X 
X1 
X 
Neurocognitive Battery 
Ensuring speech understanding test 
X 
X 
X 
X 
X 
X 
MMSE/Partial CDP Hybrid 
 
X 
 
X 
 
X 
CERAD Recall Test 
 
X 
 
X 
 
X 
Trail Making Test Part A [oral] 
 
X 
 
X 
 
X 
Trail Making Test Part B [oral] 
 
X 
 
X 
 
X 
Digit Span Backward 
 
X 
 
X 
 
X 
Word Fluency (FA) 
 
X 
 
X 
 
X 
Animal Naming 
 
X 
 
X 
 
X 
Clinical Dementia Rating Scale – Telephone 
Version of Participant Interview 
 
X 
 
X 
 
X 
Dementia/MCI evaluation if applicable2  
 
X 
 
X 
 
X 
Six-Item Screener3 
X 
X 
X 
X 
X 
X 
AD84 
X 
X 
X 
X 
X 
X 
Non-Neurocognitive Measures  
CES-D Scale 
X 
X 
 
X 
 
X 
Hearing Handicap Inventory for the Elderly - 
Screening Version 
X 
X 
 
X 
 
X 
SF-36 Health Survey 
X 
X 
 
X 
 
X 
Cohen Social Network Index 
X 
X 
 
X 
 
X 
UCLA Loneliness Scale 
X 
X 
 
X 
 
X 
Falls and mobility questionnaire 
 
X 
 
X 
 
X 
Hospitalizations 
X 
X 
X 
X 
X 
X 
Physical Activity Form 
 
X 
 
X 
 
X 
Intervention Feedback Form 
X 
 
 
 
 
X 
COVID impact questionnaire5 
 
 
X 
X 
X 
X 
SUCCESSFUL AGING INTERVENTION PARTICIPANTS ONLY 
Successful aging intervention visit/booster session 
X 
X 
X 
X 
X 
 
HEARING INTERVENTION PARTICIPANTS ONLY 
Intervention Check-up Form 
X  
X 
X 
X 
X 
X 
International Outcome Inventory for 
comprehensive intervention 
X  
X 
X 
X 
X 
X 
1. Only questions about hearing aid use. 
2. Clinical dementia rating (informant and summary) forms and neuropsychiatric interview collected from 
participant’s informant if participant meets criteria for additional data collection based on the neurocognitive 
battery. 
3. Collected at the semi-annual visits. Only collected at the annual visit if unable to collect neurocognitive data. 
4. Collected from knowledgeable informant at any visit only if participant is unable to complete the annual 
neurocognitive battery and/or the SIS. 
5. Added in January 2021. 
 
 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
62 
19.2 Modifications to neurocognitive assessment 
 
19.2.1 Neurocognitive tests with no substantive changes 
See section 7.2 for comparison of the in-person neurocognitive assessments. The content of the 
ensuring speech understanding test, the digits backwards test, and animal naming test remains 
the same as described in section 7.2 but with some modifications to instructions for telephone 
administration. The content of the CDP (see section 7.3.2) remains the same but the order of 
administration has been modified for use over the telephone. The word fluency test has been 
shortened to collect on 'F' and 'A' words. 'S' words has been dropped. 
 
19.2.2 CERAD recall 
An oral 10-item word list memory measure (CERAD, The Consortium to Establish a Registry for 
Alzheimer's Disease50) test is used in lieu of the visual Delayed Word Recall test (see section 
7.2.4). 
 
19.2.3 Shortened Mini-Mental State Exam 
This includes a subset of items from the Mini-Mental State Exam (see section 7.4.10). The 
shortened version facilitates telephone interviewing. Two questions from the original MMSE 
have been adjusted for phone administration and 19 original items have been dropped. A 
detailed script is provided for each item.  
19.2.4 Oral Trails A 
An oral version of Trails A in lieu of the visual version described in Sections 7.2.7. The 
participant is asked to count from 1 to 25 as quickly as they can. Up to 5 attempts are allowed 
for this task. The total time the participant took to complete the series, the total numbers correct 
and the total number of errors are recorded. The maximum time permitted to complete the task 
is 4 minutes. If the participant makes 5 errors then the test is stopped. 
19.2.5 Oral Trails B 
An oral version of Trails B in lieu of the visual version described in section 7.2.8. The participant 
is asked to alternate between letters and numbers as quickly as they can until they reach the 
number 13. Up to 5 attempts are allowed for this task. The total time the participant took to 
complete the series, the total numbers and letters correct, and the total number of errors are 
recorded. The maximum time permitted to complete the task is 4 minutes. If the participant 
makes 5 errors then the test is stopped. 
19.3 Addition of interim check-in calls 
As a result of COVID-19 and its effects, the ACHIEVE team is adding interim calls to 
participants initiated by the interventionist (i.e., audiologist or health educator) to occur between 
the scheduled semi-annual and annual visits (i.e., around 9, 15, 18, 21, 27, and 33 months post-

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
63 
randomization) until in-clinic visits resume. The purpose of these calls is to reinforce 
intervention-specific content (e.g., hearing aid use, health topics covered previously), check on 
participant well-being, and remind participants that the study is ongoing, though remotely, and 
we continue to value their contributions. These calls are considered both an additional retention 
tool and an adherence tool and are collected at the site’s discretion. 
20 History of protocol amendments 
Minor changes to page numbering and formatting have been made throughout the document as 
part of the protocol updates. Substantive modifications between versions are detailed below. 
Protocol 
version 
Affected section Brief description of change 
Brief rationale for change 
v1.7 
(28 Jul 2017) 
Original version of the protocol approved by site IRBs. 
v1.8 
(16 Nov 2017) 
4.2 Exclusion 
criteria 
Vision criteria changed from no 
worse than 20/40 to no worse 
than 20/63. 
The criteria for the ACHIEVE pilot 
was to read 14-point font, which 
corresponds to 20/63. It was always 
the intention to use the same criteria 
in ACHIEVE, but the corresponding 
MN acuity was inadvertently stated 
as 20/40 instead of 20/63. 
6.1 Informed 
consent 
Description of re-obtaining 
consent in the event of 
cognitive impairment was 
added. 
This information was included in the 
MOP but had been omitted from the 
protocol. 
7.5.4 SF-12v2 
Health Survey 
SF-12 survey replaced with 
SF-36 survey. 
The parent study ARIC no longer 
uses the SF-12 due to licensing 
restrictions. The SF-12 is a short 
version of the SF-36. 
7.7 Schedule of 
evaluations 
Table modified to reflect the 
correct schedule of 
evaluations. A pre-screening 
column was added, changes 
were made to some 
assessment names, and edits 
were made to when data on 
inclusion criteria and covariates 
are collected across pre-
screening, screening, and 
baseline. 
ACHIEVE Steering Committee 
decision. 
10. Strategies to 
promote 
intervention 
adherence 
Successful aging participants 
“can” bring a partner changed 
from “encouraged” to match 
with the MOP. 
The partner is not enrolled in the 
study but may accompany the 
participant to sessions. 
11.2 Adverse 
events 
Addition of “Unanticipated 
Problems” section. 
This section provides a general 
description of NIH criteria of 
unanticipated problems. 
12.1 Sample size 
calculation 
Wording of one sentence 
changed from “mixed effects” 
to “multiple imputation 
ANCOVA”. 
This sentence was inadvertently not 
updated when we modified the 
primary analysis method from a 
mixed model to multiple imputation 
ANCOVA. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
64 
v1.9 
(1 Jul 2020) 
Study Summary, 
4. Study 
population and 
eligibility 
Sample size updated to reflect 
expanded recruitment up to 
1000 participants. 
The DSMB recommended extending 
recruitment, and the NIA issued an 
administrative supplement to 
support this change. 
5.4 Retention 
strategies 
Clarified that study staff will 
determine how long to continue 
contact efforts, but that 
participants are only 
considered “withdrawn” if they 
explicitly request to withdraw. 
This is a clarification. 
7.7 Schedule of 
evaluations 
Sentence added to allow data 
collection visits to be split 
across multiple days or 
settings.  
 
The ESU form is collected at all 
follow-up visits. The table was 
updated to reflect that point. 
Other parts of the protocol already 
allowed for telephone contacts or 
home visits, but this information has 
been clearly added here to allow 
maximum flexibility to accommodate 
participants. 
9.2 Successful 
Aging intervention 
Key #10 updated to 
“Caregiving and Health”. 
This key was previously under 
development and has since been 
finalized. 
12.4 Interim 
Analysis for 
sample size re-
estimation 
 
Updated to detail the interim 
analysis that was conducted in 
June 2019 in lieu of the 
originally planned interim 
analysis. 
Changes made based on DSMB 
recommendations 
19. Changes as a 
result of COVID-
19 
NEW section added to outline 
the substantive modifications to 
ACHIEVE as a result of 
COVID-19. This section details 
the addition of telephone 
contacts and changes to 
outcome assessments. 
The COVID-19 global pandemic led 
to suspension of in-person research 
study visits to protect participants, 
staff, and the larger community from 
risk of infection from COVID-19, 
which necessitated implementing 
remote data collection procedures. 
20. History of 
protocol 
amendments 
NEW section added outlining 
prior substantive protocol 
amendments. 
It is helpful to have the full history of 
protocol changes within the current 
protocol document. 
v1.10 
(9 Nov 2021) 
5.4 Retention 
strategies 
Added that telephone visits 
may be conducted to collect 
data from participants unable 
to come to the field site. 
Telephone visits were previously 
added as a modality of data 
collection, as noted in sections 7.7 
and 19 but had not been added to 
the retention section. 
6.1 Informed 
consent 
Details on obtaining re-consent 
with a proxy, including remote 
consent, were added. 
Due to the ongoing pandemic, the 
ability to obtain consent remotely 
from a proxy was necessary for 
participants who had previously 
provided informed consent but have 
been determined to have 
significantly reduced cognitive 
capacity during the course of the 
trial. 
6.2 Participant 
confidentiality 
Details on the results provided 
to participants and their private 
physicians were updated. 
These changes reflect corrections to 
match with how the study is being 
implemented.  As ACHIEVE is a trial 
studying cognition, information 
related to cognitive impairment is 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
65 
not shared with participants.  
Audiometry results are not routinely 
shared with participants or their 
physicians (but can be shared with 
participants if requested).  The only 
results shared directly with a 
participant’s physician relate to alert 
values, and these are only shared 
with the physician if the participant 
has given approval for the results to 
be shared. 
7.4.12 COVID 
impact 
questionnaire; 
7.7 Schedule of 
evaluations; 
19.1 Remote 
visits – Table 4 
The protocol is being updated 
to reflect the addition of the 
COVID impact questionnaire 
effective January 2021 for the 
semi-annual and annual visits. 
This questionnaire was previously 
submitted and approved for use but 
had not yet been incorporated into 
the study protocol.  This brief 
questionnaire, which was based on 
the National Alzheimer’s 
Coordinating Center (NACC) 
COVID-19 Impact Survey, was 
added to understand how COVID-19 
may be affecting participants. 
7.7 Schedule of 
evaluations 
The CDP, CDI, CDS, and NPI 
were removed from the semi-
annual visits. 
The removal from the semi-annual 
visits is a correction to reflect that 
these assessments were only 
intended to be completed annually 
(and for the CDI, CDS, and NPI, 
only if applicable). 
7.7 Schedule of 
evaluations 
The Client-Orientated Scale of 
Improvement (COSI) collection 
schedule was updated to 
reflect that the goals were only 
discussed during hearing 
intervention sessions A, C, and 
D, and not at the subsequent 
semi-annual and annual visits. 
This change is a correction to reflect 
the proper timing of assessment as 
planned and implemented. 
17 Timeline 
The timeline was updated. 
The updates to the timeline reflect 
the extended recruitment period that 
was recommended by the DSMB 
and supported by an administrative 
supplement from the NIA. 
19.1 Remote 
visits 
Information regarding the split 
Year 3 visits with a delayed in-
person component after the 
field sites reopened. 
This change, which was previously 
submitted and approved, is now 
being incorporated into the protocol.  
While the field sites were closed due 
to COVID, it was necessary to split 
the Year 3 visits, with a delayed in-
person visit after the field sites 
reopened, to allow for the best 
quality data for the primary 
endpoint, consistent with the 
baseline in-person measurement.  
Having a delayed in-person visit 
also allowed for delivery of the other 
study intervention upon trial 
completion, as was promised to 
participants. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
66 
22 Appendix A 
This section was added to 
detail the delivery of the other 
intervention to participants 
upon their completion of the 
ACHIEVE Trial. 
The protocol and consent stated 
that participants would be able to 
receive the other intervention (i.e., 
the successful aging intervention for 
participants originally randomized to 
the hearing intervention, or vice 
versa) upon completion of their final 
(Year 3) ACHIEVE visit.  Although 
the descriptions of the interventions 
were previously outlined in protocol 
section 9 as they related to the trial, 
the protocol did not previously 
specifically address what the 
delivery of the other interventions 
would look like after participants had 
already completed the trial. 
23 Appendix B 
This section was added to 
describe optional extended 
follow-up of the participants 
randomized to the successful 
aging group after completing 
the ACHIEVE trial and 
receiving hearing aids and the 
hearing intervention program. 
We would like to learn how receiving 
hearing aids affects the participants’ 
hearing and communication, as well 
as social, mental, physical, and 
overall well-being.  We would also 
like to understand how much 
participants use their hearing aids 
and the hearing care support from 
the study audiologists.  Participants 
will be asked to provide consent to 
(a) allow the study to use 
information related to the delivery of 
their hearing aids and hearing 
support as part of their research 
record, and (b) participate in 
additional data collection 
assessments similar to what has 
been collected during their 
ACHIEVE visits. 
 
 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
67 
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22 Appendix A:  Delivery of the Other Intervention after Completing ACHIEVE Trial 
22.1 Successful Aging intervention for participants originally randomized to the 
hearing intervention group 
22.1.1 Overview 
Upon completion of the Year 3 ACHIEVE visit, all participants from the hearing intervention 
group will be offered a binder containing the Successful Aging intervention program materials on 
topics important for healthy aging (see section 9.2 Successful Aging intervention for an overview 
of the program). 
Participants will be offered that they can choose to receive a follow-up call from the health 
educator.  They can also choose to schedule an in-person session with the health educator to 
review health goals relevant to them.   
22.1.2 Schedule of activities 
Completion of any follow-up calls or in-person sessions with the health educator is considered 
optional, at the participant’s discretion.  The timing of any follow-up sessions is flexible, and 
there are no set windows for when the sessions must occur, but are generally encouraged to 
occur within 1-2 months of receiving the binder. 
22.2 Hearing intervention for participants originally randomized to the Successful 
Aging intervention group 
22.2.1 Overview 
Upon completion of the Year 3 ACHIEVE visit, all participants from the successful aging 
intervention group will be offered to receive the comprehensive hearing intervention program, 
including hearing aids and other devices customized to participants’ hearing needs and listening 
goals, along with follow-up care for 6 months. 
22.2.2 Blended telehealth hearing health care delivery model 
Participants receiving the hearing intervention program after completion of the successful aging 
program will be offered a comparable, though different, hearing intervention program than the 
participants initially randomized to the hearing intervention program.  These participants will 
receive hearing aids that are compatible with remote hearing aid programming.  Participants will 
be encouraged to receive their hearing intervention sessions remotely via telehealth.  
Participants may receive these sessions in person, if preferred by the participant or if the 
participant does not meet the technological requirements for telehealth (i.e., internet connection, 
smart device).  
 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
72 
22.2.3 Schedule of activities for delivery of the hearing intervention to SA participants after 
completing ACHIEVE 
 
Hearing Intervention Sessiona 
6-month 
check-up 
Assessment 
A 
Bb 
Cc 
Dd 
Instructions for telehealth 
X 
 
 
 
 
Hearing aid dispensing, programming, and 
instruction in care and use 
X 
 
 
 
 
HAT dispensing 
Xe 
Xe 
Xe 
Xe 
 
Counseling, education, and self-management 
support 
X 
X 
X 
X 
 
SA Intervention check-up 
X 
X 
X 
X 
X 
International Outcome Inventory for 
Comprehensive Hearing Intervention (IOI-CHI) 
 
 
 
X 
 
Client-Oriented Scale of Improvement (COSI) 
goal setting 
X 
 
 
 
 
COSI goals achievement 
 
 
 
X 
 
Telehealth acceptance pre-intervention (TAP) 
X 
 
 
 
 
aHearing intervention session A will be conducted in person.  Sessions B, C, and D will be conducted 
remotely using telehealth unless participant or staff preference is in-person sessions. 
bSession B will occur approximately 3 weeks after Session A. 
cSession C will occur approximately 6 weeks after Session A. 
dSession D will occur approximately 8 weeks after Session A. 
eHAT dispensing is expected to occur during the hearing intervention program sessions, but the specific 
session(s) when it occurs may vary depending upon participant goals. 
22.2.4 Procedures 
The activities and assessments listed in the table above are intended to be used by the 
audiologists to deliver the hearing intervention.  These activities and assessments, with the 
exception of telehealth components (instruction in telehealth and the telehealth acceptance pre-
intervention questionnaire), mirror those of the hearing intervention that the participants 
originally randomized to the hearing intervention received. 
The telehealth acceptance pre-intervention questionnaire (TAP) questionnaire assesses the 
participant’s comfort with and acceptance of telehealth HHC prior to start of the telehealth 
intervention, in order to help guide the audiologist in determining whether remote or in-person 
sessions may be a better fit for the participant or where additional instruction related to 
telehealth may be needed. 
The hearing intervention program will be similar to what was described in section 9.1 above. 
Session A will occur in person and involves providing an overview of the participant’s hearing 
loss, determining the participant’s level of comfort with telehealth, setting goals using the Client 
Oriented Scale of Improvement (COSI), fitting the hearing aids using best practices, providing 
orientation for how to use the devices, determining which sections of the ACHIEVE-HI Toolkit 
for Self-Management© and RLO videos best relate to the participant’s needs, and orienting the 
participant to eAudiology and myPhonak applications. 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
73 
Session B focuses on management and troubleshooting of hearing aids and HATs, including 
any need for fine-tuning of device settings, and counseling for self-management, including 
reviewing the “Hearing Loss and Your Listening Goals” and the “Communication Strategies” 
Toolkit sections.  It is at Session B that the intervention becomes more individualized based on 
the unique needs and experiences of the participant.  Session B will default to a telehealth 
session but can be completed as an in-person session if necessary. 
Session C is similar to Session B.  Session C will default to a telehealth session but can be 
completed as an in-person session if necessary. 
Session D is similar to Session C and also involves completion of the IOI-CHI. 
Around 6 months after Session A, participants will return to the clinic for an in-person visit to 
check whether the participant has any questions or concerns related to their listening goals, the 
hearing aids, or hearing assistive technologies. 
 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
74 
23 Appendix B:  Extended Follow-Up of Successful Aging Participants after Delivery of 
the Hearing Intervention 
Note:  The Hearing Intervention participants are already being offered extended follow-up as 
part of a separate trial (Randomized Trial of Telehealth vs. Conventional Hearing Care Delivery 
in the ACHIEVE Study [ACHIEVE-HIFU]; R01DC019408; IRB00284937 [JHU sIRB]).   
23.1 Background and rationale 
As part of participation in the ACHIEVE trial, upon completion of the final Year 3 visit, 
participants are offered the intervention that they were not initially randomized to receive (i.e., 
participants who were randomized to receive the hearing intervention program are offered the 
successful aging education program, and vice versa – see section 22 Appendix A:  Delivery of 
the Other Intervention after Completing ACHIEVE Trial).  For the successful aging participants 
who receive the hearing intervention program after Year 3, we would like to learn how receiving 
hearing aids affects the participants’ hearing and communication, as well as social, mental, 
physical, and overall well-being.  We also want to understand how much participants use their 
hearing aids and the hearing care support from the study audiologists, as well as the modality of 
hearing care support (telehealth vs. in-person). 
23.2 Participants 
To be eligible for the extended follow-up, participants must: 
1) have been eligible for and participated in the successful aging intervention arm of the 
ACHIEVE trial, 
2) agree to receive the hearing intervention program, and  
3) be able and willing to participate in this extended follow-up (i.e., provide separate 
consent for the extended follow-up). 
ACHIEVE participants who have developed cognitive impairment are eligible for the extended 
follow-up visits if they are willing to participate and are consented with a proxy (see section 6.1 
Informed consent). 
 
 

ACHIEVE Protocol, v.1.11 March 23, 2023 
 
75 
23.3 Schedule of activities 
 42-month 
Year 4 
Informed consent 
Xa 
 
Hearing Intervention 
SA Intervention check-up 
X 
X 
International Outcome Inventory for Comprehensive Hearing 
Intervention 
X 
X 
Audiometry 
Air conduction audiometry 
 
X 
Bone conduction audiometry 
 
Xb 
Tympanometry 
 
X 
Word Recognition in Quiet 
 
X 
Quick Speech in Noise (unaided) 
 
X 
Social, Mental, and Physical Outcomes 
CES-D Scale 
X 
X 
Hearing Handicap Inventory for the Elderly - Screening Version 
X 
X 
RAND-36 Health Survey 
X 
X 
Cohen Social Network Index 
X 
X 
UCLA Loneliness Scale 
X 
X 
Hospitalizations 
X 
X 
Qualifying (S)AE assessment 
X 
X 
Abbreviated neurocognitive batteryc 
X 
 
Full neurocognitive batteryd 
 
X 
Clinical Dementia Rating Scale - Participant (CDP) 
 
X 
Dementia/MCI evaluation if applicable (CDI, CDS, NPI) 
 
Xb 
Baecke activity questionnaire 
 
X 
Falls and mobility questionnaire 
 
X 
Accelerometry 
 
X 
Grip strength 
 
X 
Short Physical Performance Battery 
 
X 
Covariates 
Health history 
 
X 
Neurologic history 
 
X 
Anthropometry 
 
X 
Seated blood pressure 
 
X 
COVID impact questionnaire 
X 
X 
Telehealth acceptance post-intervention (TAF) 
X 
X 
aInformed consent can occur following the ACHIEVE Year 3 visit, at Hearing Intervention Session A, or at 
the 42-month visit prior to any data collection. 
bProcedures that are intermittent based on protocol. 
cEnsuring Speech Understanding (ESU) and MMSE only. 
dESU, MMSE, Delayed Word Recall Test, Digit Symbol Substitution Test, Incidental Learning, Trail 
Making Test Part A and Part B, Logical Memory I and II, Digit Span Backward, Boston Naming Test, 
Word Fluency (FAS), and Animal Naming. 
23.4 Procedures 
See section 7 Data collection and measurements for descriptions of all procedures, except for 
the telehealth acceptance questionnaire post-intervention.  The telehealth acceptance post-
intervention questionnaire (TAF) is an interviewer-administered questionnaire that assesses the 

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participant’s comfort with and acceptance of telehealth hearing health care after starting the 
telehealth intervention. 
As part of participation in this extended follow-up, participants will be able to continue receiving 
hearing follow-up care from the study audiologist (e.g., maintenance, adjustments, counseling, 
monitoring of listening goals) for an additional 6 months beyond what was covered as part of the 
delivery of the other intervention (i.e., for 1 year after receiving the hearing aids).  For each 
participant issue, the audiologist will document the modality of support provided (e.g., 
telephone, video call, clinic visit, hybrid), the number and duration of the encounters, the type of 
issue, and its resolution. 
23.5 Safety 
As only one questionnaire (TAF) has been added vs. what was collected in the main ACHIEVE 
trial, there are no new risks associated with extended follow-up.