Cognitive Rehabilitation for Older Veterans With Mild Cognitive Impairment
Phase: NA
Conditions: Mild Cognitive Impairment
Sponsor: VA Office of Research and Development

Cognitive Rehabilitation for Older 
Veterans with Mild Cognitive Impairment
NCT03225482
April 13, 2021

Human Protocol (Version 1.17)
General Information
*Please enter the full title of your protocol:
Cognitive Rehabilitation for Older Veterans with Mild Cognitive Impairment
 
 
*Please provide a short name (nickname) to reference this protocol:
CCT for MCI
* This field allows you to enter an abbreviated version of the Protocol Title to quickly identify 
this protocol.
 
 
Add Site(s)
VA Site (************** DO NOT ADD OR CHANGE, just save and continue **************):
Primary 
Dept?
Department Name
VASDHS - VASDHS
 
Identify protocol staff members
*Please add a Principal Investigator for the study:
 
Twamley, Elizabeth W., PhD
 
3.1 Add all other VA research staff personnel (if name is not in the list, please contact Research 
Staffing to confirm appointment status)
 
A) Additional Investigators
Jak, Amy J., PhD 
 Co-Investigator
B) Research Support Staff
Clark, Jillian, PhD 
 Post-Doc
Contreras, Ingrid 
 Study Coordinator
Green, Chloe T., PhD 
 Research Associate
Hernandez, Jeffrey 
 Research Associate
Jurick Lefler, Sarah, PhD 
 Research Associate with no PHI access
N

Keller, Amber Victoria 
 Study Coordinator
Lykins, Hannah 
 Study Coordinator
Mahmood, Zanjbeel, BA 
 Research Associate
Maye, Jacqueline, PhD 
 Post-Doc
Morgan, Matthew R. 
 Research Associate
Muller-Cohn, Chantal, BA 
 Research Associate
Parikh, Mili, PhD 
 Research Associate
Pickell, Delaney Q. 
 Research Associate
Seewald, Paula Michelle, MA 
 Study Coordinator
Van Patten, Ryan 
 Post-Doc
Wyckoff, Janae Ruth 
 Research Associate
*Please select the Research Contact(s)
 
Twamley, Elizabeth W., PhD 
The Research Contact(s) will receive all important system notifications along with the Principal 
Investigator. (Research Contacts are typically Study Coordinators or the Principal Investigator 
themselves).
 
VASDHS - IRB Protocol
v20150312
 - Preliminaries
Section 1
Principal Investigator:
Elizabeth W. Twamley, PhD
Protocol Title:
Cognitive Rehabilitation for Older Veterans with Mild Cognitive Impairment
IRB Protocol Number:
H170016
Protocol Nickname:
CCT for MCI
Form Template Version:
v20150115
Date Prepared:
04/06/2021
 Is this study considered human research?
1a)

 Yes   
 No
 Is this a request for a determination of exemption from IRB review?
1b)
  Yes   
  No
 Is this a request for an expedited IRB review?
1c)
  Yes   
  No
 
New Protocol or Transfer/Renewal of Prior Protocol
1.3 
Section 
 Select the type of protocol application:
1.3)
Is this a new protocol?  (if transfer to VA IRB, select 
)
1.3a) 
No
 Yes   
 No
 Is this a resubmission of a VASDHS IRB protocol?
1.3b)
  Yes   
  No
 Is this a transfer of a protocol to the VASDHS IRB?
1.3c)
  Yes   
  No
 
 - Research Subjects
Section 2
 What is the total planned number of VASDHS-consented subjects needed?
2a)
(Include even if using a waiver of documented consent, e.g. oral consents)
108
 What is the total number of VASDHS subjects needed that WILL NOT be consented (e.g., 
2b)
retrospective reviews) ?
0
 
Consented Subject Groups
2.1 
Section 
 For each of the subject categories listed below, indicate whether or not these subjects will be 
2.1)
enrolled (consented) in the study: (exclude cases of data or specimens only)
 Children under age 18
2.1a)
  Yes   
  No
 Women of child-bearing potential
2.1b)
  Yes   
  No
 Pregnant women
2.1c)
  Yes   
  No

 Individuals with cognitive/decisional impairment
2.1d)
 Yes   
 No
 Non-English speaking individuals
2.1e)
  Yes   
  No
 Prisoners of War [explicitly targeting this group]
2.1f)
  Yes   
  No
 Non-Veterans (Note: A justification will be required below)
2.1g)
  Yes   
  No
 Incarcerated individuals (Note:  VA CRADO approval will be required)
2.1h)
  Yes   
  No
 VA employees (or WOCs)
2.1i)
  Yes   
  No
 Students
2.1j)
  Yes   
  No
 Patients with cancer (or high cancer risk) [explicitly targeting this group]
2.1k)
  Yes   
  No
 
 - Study Features
Section 3
       (these items default to "No" for convenience)
This section consists of several Yes/No questions addressing protocol characteristics.    
3) 
   Click on Save 
.
and Continue
 
Protocol Basics
3.1 
Section 
Indicate whether or not each of the following applies to this protocol
 The research 
 the participant
3.1a)
intends to change
 Yes   
 No
 with living participants to collect data or specimens with no intent to change them.
3.1b) Interactions
  Yes   
  No
This is a study that 
 has any 
 (e.g., de-identified 
3.1c) 
never
subject contact or subject identifiers
tissue only).
  Yes   
  No
 This is a 
 study (multiple IRB's involved) and 
 is the 
 or a coordinating site
3.1d)
multi-site
VASDHS
main
 Yes   
 No
This is a 
study (multiple IRB's involved) and VASDHS is NOT the main or a coordinating 
3.1e) 
multi-site 
site
  Yes   
  No
There is an 
 component to this research
3.1f) 
international

  Yes   
  No
Any study activity occurs at 
(not including VHASDC leased space or 
3.1g) 
non-VASDHS locations 
clinics) under the VASDHS IRB protocol.
  Yes   
  No
VASDHS subjects 
 in whole or in part 
 (not including VHASDC leased 
3.1h) 
participate
at other locations
space or clinics) under this VASDHS IRB protocol.
  Yes   
  No
 
Specimen Use and Data Repository
3.2 
Section 
Indicate whether or not each of the following applies to this protocol
Involves specimens that are left over from pathological or diagnostic testing (
3.2a) 
non-research 
)
specimens
  Yes   
  No
Involves 
 purposes 
3.2b) 
specimens collected for research
only
  Yes   
  No
This study includes 
 (specimens are retained for use outside of the purposes of 
3.2c) 
specimen banking
this protocol)
  Yes   
  No
The study involves 
genotyping or other 
3.2d) 
DNA 
genetic analysis
  Yes   
  No
A Biological 
Agreement is required.
3.2e) 
Materials Transfer 
  Yes   
  No
A 
 is maintained (data are retained after completion of the protocol for other uses, 
3.2f) 
data repository
 see  before checking "yes")
IMPORTANT
?
  Yes   
  No
 
Treatment and Clinical Trials
3.3 
Section 
Indicate whether or not each of the following applies to this protocol
Includes a 
 component 
3.3a) 
treatment
(a research treatment)
 Yes   
 No
Study is a 
3.3b) 
clinical trial
 Yes   
 No
Has a data safety monitoring board (
or data safety monitoring committee
3.3c) 
DSMB) 
  Yes   
  No
 Has a 
 (but not a DSMB) 
3.3d)
data safety monitoring plan
(this is not the data security plan, it is a 
safety plan)
 Yes   
 No

 
Drugs and Devices
3.4 
Section 
Indicate whether or not each of the following applies to this protocol
 that require 
 action such as an Investigational New Drug (IND) approval or exemption 
3.4a) Drugs
FDA
or 510(k) approval.
  Yes   
  No
Other drugs that
action for inclusion in the study
3.4b) 
 do not require FDA 
  Yes   
  No
 Medical 
 IDE approval or waiver
3.4c)
devices requiring FDA
  Yes   
  No
 medical 
3.4d) Other
devices
  Yes   
  No
 
 Risk and Hazards
3.5
Section 
Indicate whether or not each of the following applies to this protocol
 Study places subjects at 
3.5a)
greater than minimal risk (do not include risks that are due to standard 
care)
  Yes   
  No
 Human subjects are exposed to 
 (do not include standard care)
3.5b)
radioisotopes
  Yes   
  No
 Subjects have other 
 (e.g., x-rays) (do not include standard clinical use)
3.5c)
radiation exposure
  Yes   
  No
Target population has psychiatric diagnosis or behavioral complaint.
3.5d) 
 Yes   
 No
 
Clinical Facilities and Standard Care
3.6 
Section 
Indicate whether or not each of the following applies to this protocol
 Study 
 (e.g., adds required tests run in the VA lab for study purposes)
3.6a)
uses VA clinical services
  Yes   
  No
 Includes procedures or drugs that will be considered 
3.6b)
part of standard care
  Yes   
  No
Involves 
purposes
3.6c) 
lab tests done for research 
  Yes   
  No
 
Subject Expenses and Compensation
3.7 
Section 

Indicate whether or not each of the following applies to this protocol
There may be expense or added 
or the subject's insurance.
3.7a) 
costs to the subject 
  Yes   
  No
 This is a 
 and subjects may be billed for study drugs or 
3.7b)
qualifying cancer treatment trial
procedures.
  Yes   
  No
This is a cancer treatment trial but 
 for study drugs or procedures.
3.7c) 
subjects will not be billed
  Yes   
  No
 Subjects will be
(either in cash or other means such as a gift certificate)?
3.7d)
 compensated 
 Yes   
 No
 
Subject Activities
3.8 
Section 
Indicate whether or not each of the following applies to this protocol
 Involves 
 completed by subjects
3.8a)
surveys or questionnaires
 Yes   
 No
 Includes the use of 
 such as flyers, advertisements, or letters
3.8b)
recruitment materials
 Yes   
 No
 Involves facial 
 or audio or video 
of 
3.8c)
photographs
recordings 
patients
 Yes   
 No
 
Sponsors and Collaboration
3.9 
Section 
Indicate whether or not each of the following applies to this protocol
This research has a 
3.9a) 
commercial (industry) sponsor.
  Yes   
  No
Other 
is provided (e.g., drugs or supplies).
3.9b) 
commercial (industry) non-financial support 
  Yes   
  No
The PI or other study staff member has a financial interest or other
3.9c) 
 real or potential conflict 
related to this study.
  Yes   
  No
The protocol has 
 involvement (e.g., subjects or funding).
3.9d) 
Department of Defense
  Yes   
  No
(either researchers or entities, not VA WOCs, can be VA 
3.9e) Non-VASDHS Research collaborators 
Other service also) are involved in this VASDHS IRB protocol. (Generally they cannot have access to 
sensitive information)
  Yes   
  No

 
 - Estimated Duration
Section 4
What is the estimated duration of the entire study?  
4) 
(From IRB approval to IRB closure)
6 years
 
 - Lay Language Summary
Section 5
Provide a summary or synopsis of the proposed study using non-technical language 
5) 
(not more than 1 
paragraph)
Due to the aging of the United States population, age-related cognitive problems resulting from Alzheimer’
s disease and other causes of dementia are increasingly prevalent. Before individuals are diagnosed with 
dementia, they typically exhibit a period of “mild cognitive impairment” (MCI). Mild cognitive problems 
associated with MCI frequently impact an individual’s ability to perform everyday tasks, including working, 
independent living, and medication adherence. Veterans are at increased risk of cognitive decline, and the 
Veterans Healthcare Administration (VA) is now providing health care to surging numbers of older 
Veterans with MCI who report significant cognitive complaints, difficulties with everyday functioning, and 
concerns about impending dementia. Despite high patient demand, few cognitive rehabilitation 
interventions exist that specifically address the needs of older Veterans with MCI that are widely 
accessible, patient-centered, and evidence-based. To our knowledge, no randomized controlled trials have 
been conducted that evaluate the efficacy of manualized, brief and inexpensive, yet comprehensive (multi-
modal) cognitive rehabilitation interventions for older Veterans with MCI. Hence, the primary objective of 
this study is to evaluate the efficacy of Motivationally Enhanced Compensatory Cognitive Training (ME-
CCT), a manualized cognitive rehabilitation group treatment for older Veterans with MCI. The study’s 
specific aims are to determine whether ME-CCT is effective for: 1) improving objective cognitive 
performance and functional capacity, 2) improving subjective cognitive complaints, subjective functioning, 
and collateral measures of everyday function, and 3) increasing modifiable protective factors (e.g., diet, 
exercise) associated with reduced risk for MCI. We will also explore mediators and moderators of 
treatment effects. The overall goal is to evaluate a manualized group treatment for the symptoms of MCI 
that can be readily implemented in VA treatment settings. The study design makes use of the convergent 
availability of resources at the two participating VA Healthcare Systems in San Diego, California and 
Portland, Oregon to conduct a randomized controlled trial of ME-CCT. The study will recruit a sample of 
216 Veterans (108 at each site) who meet criteria for MCI. Inclusion criteria will be: 1) Veterans 55 years 
old or older enrolled at one of the participating VAs who are able to provide informed consent, 2) 
Independently living, 3) Meet criteria for MCI based on previously published criteria (Petersen, 2004; 
Petersen, 2011), and 4) Willingness to participate in audio-recorded group sessions. Exclusion criteria will 
be: 1) Current substance use disorder with less than 30 days abstinence, 2) History of schizophrenia, 
schizoaffective disorder, or other primary psychotic disorder, 3) History of significant head trauma with 
loss of consciousness >30 minutes, and 4) Auditory or visual impairments that would prevent ability to 
participate in the cognitive rehabilitation group. Eligible participants will be randomly assigned to either 
the ME-CCT or an active control group, Goal-focused Supportive Contact (SC). The SC group will provide 
the same frequency and amount of therapist and peer contact as ME-CCT, but without specific training in 
cognitive strategies, lifestyle strategies, or motivational enhancement. 8 2-hour long weekly sessions will 
be delivered in both conditions. Both groups will undergo evaluations at baseline, 4 weeks (midway 
through the intervention), 8 weeks (immediately following the end of the intervention), and 21 weeks (3 
months after completion of the intervention).
 
 - Specific Aims
Section 6
Provide a statement of specific aims and 
 that serve as the basis for this 
6) 
hypotheses
protocol.  Emphasize those aspects that justify the use of human subjects.
Due to the aging of the United States population, age-related cognitive problems resulting from Mild 
Cognitive Impairment (MCI), Alzheimer's disease, and other causes of dementia are increasingly 
prevalent. Before individuals are diagnosed with dementia, they typically exhibit a period of MCI. Mild 
cognitive problems associated with MCI frequently impact an individual's ability to optimally perform 
everyday tasks, including working, tasks of independent living, and medication adherence. Veterans are at 
increased risk of cognitive decline, and older Veterans diagnosed with posttraumatic stress disorder 
(PTSD) are twice as likely to have a diagnosis of dementia as individuals without PTSD. Hence, the 
Veterans Healthcare Administration (VA) is now providing health care to surging numbers of older 
Veterans with MCI who report significant cognitive complaints, difficulties with everyday functioning, and 
concerns about impending dementia. Despite high patient demand, few cognitive rehabilitation 

interventions exist that specifically address the needs of older adults with MCI and that are widely 
accessible, patient-centered, and evidence-based. Although several clinical trials are currently evaluating 
behavioral interventions for MCI, they assess highly focused interventions (e.g., attention training) which 
are unlikely to effectively address the broader range of impairments (e.g., memory, attention, executive 
function, everyday functioning) and cognitive risk factors (e.g., low physical and mental activity levels) 
that adults with MCI commonly report. Alternatively, they evaluate highly intensive and therefore 
expensive interventions (>100 hours), which are not likely to be feasible for broad numbers of Veterans 
across typical VA facilities nationally. Accessible (e.g., brief, manualized), holistic/comprehensive, and 
effective treatments for rising numbers of Veterans with MCI are urgently needed. 
Our study team recently completed a randomized controlled trial (RCT) that demonstrates the efficacy of 
our manualized, group-based, 10-week (two hours per week), Compensatory Cognitive Training (CCT) 
intervention for OEF/OIF Veterans with mild traumatic brain injury (TBI). CCT is a brief, inexpensive, 
patient centered, and holistic/comprehensive multi-modal behavioral intervention. Because Veterans with 
mild TBI have cognitive impairments similar to those seen in older Veterans with MCI, we conducted a 
small pilot study demonstrating the feasibility and acceptability of Motivationally Enhanced CCT (ME-CCT), 
which is our 8-week revision of CCT specifically adapted for the needs of older Veterans with MCI. In 
addition to compensatory cognitive training, ME-CCT includes motivational interviewing tools to boost the 
adoption of lifestyle strategies (e.g., diet, exercise) that improve cognition. Thus, the proposed RCT will 
extend our research and allow us to evaluate the efficacy of our intervention in a large sample of older 
Veterans with MCI. We will compare ME-CCT to Goal-Focused Supportive Contact (SC) for 8 weeks, 
followed by a 3 month follow-up period. 
Aim 1: To determine whether ME-CCT is effective for improving objective cognitive performance and 
functional capacity (co-primary outcomes) in older Veterans with MCI. Hypothesis 1: Compared to those 
in SC, participants in ME-CCT will show significant improvements in objective cognitive performance and 
functional capacity.
Aim 2: To determine whether ME-CCT is effective for improving secondary outcomes in older Veterans 
with MCI. Hypothesis 2: Compared to those in the SC control group, participants in ME-CCT will show 
significant improvements on measures of subjective cognitive complaints, subjective functioning, and 
collateral measures of everyday functioning.
Aim 3: To determine whether ME-CCT is effective for increasing modifiable protective factors (i.e., 
physical exercise and mental exercise) associated with reduced risk for MCI and dementia. Hypothesis 3: 
Compared to those in SC, participants in ME-CCT will show increased participation in protective activities, 
as measured by physical and cognitive activity inventories.
Exploratory Aim 4 (Mediation and Moderation): As a preliminary evaluation of mechanism, we will conduct 
exploratory analyses to evaluate whether increased use of compensatory cognitive strategies and 
increased physical and cognitive activity mediate improvements in objective cognitive performance and 
functional capacity. In order to preliminarily explore for whom this intervention is most effective, we will 
evaluate whether baseline variables (i.e., demographics, premorbid IQ, baseline health and psychiatric 
status, medication and substance use) or baseline performance on primary and secondary endpoint 
measures moderate ME-CCT-associated improvements in objective cognitive performance and functional 
capacity. 
This study addresses the significant gap in services and evidence-based treatments for aging Veterans 
with MCI. The overall impact of this project is the potential to yield a manualized, empirically-validated, 
highly feasible, person-centered intervention that meets the needs of surging numbers of older Veterans 
with MCI across the United States. If found to be efficacious, our study team will work with VA Central 
Office leaders toward national dissemination and scale-up of the ME-CCT for MCI intervention. 
 
 - Background and Significance
Section 7
Provide a succinct discussion of relevant background information to justify performing the proposed 
7) 
study.
 Due to the aging of the United States population over the past few decades, cognitive problems 
1) Scope of the problem.
such as Mild Cognitive Impairment (MCI), dementia, and Alzheimer's disease are becoming more prevalent among the 
elderly. Hence, the Department of Veterans Affairs (VA) is faced with providing healthcare for an increasing number of 
MCI is an intermediate stage between normal 
elderly Veterans who are beginning to exhibit signs of cognitive decline. 
aging and dementia [8] and is the prodromal stage for a variety of dementing neurodegenerative disorders [9]. Over 5 
million Americans currently have Alzheimer’s disease, the most common form of dementia; 35 years from now, that 
number is expected to more than triple to 16 million [10]. Alzheimer’s disease is the costliest disease in the country, at 
$214 billion per year; 35 years from now, that cost will be $1.2 trillion per year [10]. Given the personal, family, societal, 
and fiscal costs of dementia, interventions to slow the onset of dementia are urgently needed.

 
 MCI is frequently classified 
2) There is no single cause of MCI, but risk and protective factors have been identified.
into subtypes based on whether cognitive deficits are amnestic versus non-amnestic, and whether deficits affect a single 
cognitive domain versus multiple domains [9]. MCI has been demonstrated to precede various dementing 
neurodegenerative disorders. There are numerous risk and protective factors associated with MCI [1] (see 
). The 
Table 1
risk and protective factors for conversion to dementia have been shown to be similar to the risk and protective factors for 
the development of MCI [11-15].
 
Table 1. Risk and Protective Factors Associated with Mild Cognitive Impairment (MCI)
Demographic Risk Factors
Older age
Lower education
African American
Genetic Risk Factors
Family history, the presence of apolipoprotein E #4 allele (APOE)
Disease Risk Factors
Cardiovascular disease, high cholesterol, high blood pressure
Metabolic and endocrine diseases, diabetes mellitus, thyroid dysfunction
Chronic renal failure
Psychiatric disorder, depression, psychosis
Sleep disorder
Polypharmacy
Vitamin B12 deficiency
Negative Lifestyle Factors
Smoking
Heavy alcohol consumption
Positive Lifestyle Factors
Physical activity, exercise
Cognitively-stimulating activity and mental exercise
Healthy nutrition, Mediterranean diet
Note: See Huckans et al. (2013) [1] for a review and individual references supporting each factor.
 
3) Individuals with MCI report increased neuropsychiatric symptoms, reduced everyday functioning, and reduced 
Although Petersen’s [9, 16] widely accepted 
quality of life (QOL), and they are at risk for increasing disability. 
diagnostic criteria stipulate that individuals with MCI should have no more than minimal functional impairment, research 
suggests individuals with MCI nevertheless demonstrate changes in their psychological and everyday functioning [17, 18]. 
Neuropsychiatric symptoms are very common in individuals with MCI, with prevalence rates of at least one symptom 
ranging from 35-85% [19]. The most common neuropsychiatric issues associated with MCI are depression, anxiety, 
irritability, agitation, apathy, euphoria, disinhibition, delusions, hallucinations, and sleep disorders [19-22]. Areas of 
everyday functioning most frequently affected by MCI include appointment scheduling/attendance, transportation, and 
financial and medication management [23]. Individuals with MCI also report reduced QOL relative to older adults without 
cognitive impairment; reduced QOL is associated with increased neuropsychiatric symptoms and reduced functioning [24]. 
Annual conversion rates of MCI to dementia range from 10-15% in clinical samples [25].
 
Pharmacologic interventions for MCI are based on current treatment 
4) Medications have shown minimal benefit. 
guidelines for the management of Alzheimer's disease and have primarily focused on administering acetylcholinesterase 
inhibitors or other compounds to individuals with MCI in order to lower the rate of conversion to dementia [26]. The majority 
of findings from these studies indicate that acetylcholinesterase inhibitors, Vitamin E, rofecoxib, and piracetam do not 
significantly lower the rate of progression to dementia [27-29]. Given the lack of pharmacologic efficacy for MCI, non-
pharmacologic interventions have been receiving increased attention over the past decade [12, 30].
 
Cognitive 
5) Evidence supports the effectiveness of behavioral treatments, namely cognitive rehabilitation therapy. 
rehabilitation therapies can improve cognitive functioning to slow the onset of disability and prolong the independence of 
individuals with prodromal dementia [31]. Cognitive rehabilitation therapies for MCI include behavioral interventions such 
as cognitive training, psychotherapeutic, and lifestyle techniques. Cognitive rehabilitation therapies for MCI have been 
associated with improvements in subjective cognitive complaints, objective cognitive performance (e.g., memory and 
problem-solving), Independent Activities of Daily Living (IADLs), mood, and QOL; mechanisms of these effects have 
included increases in choline and creatine signals in the hippocampus and increased activation in frontal and parieto-
occipital regions of the brain [32-49]. Two studies have examined long-term effects (6 months post-treatment) of cognitive 
training, finding continued gains in QOL, work performance, objective processing speed, and memory appraisal [42, 45]. Th
ese results suggest that individuals with MCI demonstrate learning potential and cognitive plasticity, and can benefit from 
interventions [32, 50]. The bulk of the evidence from both randomized controlled trials (RCTs) and 
cognitive 
epidemiological studies suggests that positive lifestyle factors can also improve cognition and lower risk of dementia in 
adults with MCI [51]. In particular, cognitively-stimulating activities, physical exercise, and diet can improve objective 
cognitive performance in adults with MCI [51]. In our own recently published systematic review on this topic [1], we 

evaluated the efficacy of cognitive rehabilitation therapies for MCI. The bulk of the evidence suggested that cognitive 
rehabilitation therapies, including those incorporating cognitive training, psychotherapeutic, and/or lifestyle techniques, can 
change targeted behaviors in individuals with MCI and that cognitive rehabilitation therapies are associated with 
improvements in objective cognitive performance. Relatively few studies evaluated other important outcomes such as 
subjective cognitive complaints, everyday functioning, functional capacity, or neuropsychiatric symptom severity. We 
concluded that additional well-designed and adequately powered trials are warranted and required before cognitive 
rehabilitation therapies for MCI can be considered evidence-based. Our proposed trial will, therefore, address this gap and 
advance the field toward establishment of an evidence-based intervention for a rapidly growing population of older adults 
with MCI.
 
6) A comprehensive multimodal cognitive approach, as opposed to a single domain cognitive rehabilitation 
Because individuals with MCI represent a 
intervention, will better address the diverse needs of Veterans with MCI. 
heterogeneous sample and may present with a wide variety of cognitive, functional, and neuropsychiatric problems [19, 
22], MCI has been broken into four subtypes in order to improve accuracy of diagnosis and prediction of conversion to 
dementia [9]. The subtypes are determined by the type of cognitive impairment the individual with MCI is demonstrating: 
amnestic vs. nonamnestic, and single domain impairment vs. multi-domain impairment [9]. Impairment can be seen in 
virtually all cognitive domains including memory, language, attention, visuospatial functioning, and executive functions [52]. 
Because of the heterogeneity of cognitive impairments noted in MCI populations, multi-modal cognitive training 
techniques, as opposed to single domain cognitive interventions, are needed to fully address their rehabilitation needs. In 
addition to improving cognitive functioning, rehabilitation interventions should also include healthy lifestyle strategies and 
techniques to reduce emotional distress, as these can both decrease risk for the development of dementia [53]. We found 
in our systematic review of cognitive rehabilitation for MCI that improvements in objective cognitive functioning were highly 
associated with multi-modal as opposed to single-domain cognitive training interventions [1]. Based on these results, we 
are confident that our decision to make our Motivationally Enhanced Compensatory Cognitive Training (ME-CCT) 
intervention comprehensive (i.e., includes cognitive training, psychotherapeutic, and lifestyle techniques) and to include 
multi-modal compensatory cognitive training techniques (i.e., teaches skills to address attention, memory and executive 
function problems) offers the greatest potential to effectively treat MCI.
 
The VA/Department of Defense (DoD) does 
7) Clinical practice guidelines have not been adequately implemented. 
not currently have a published practice guideline for the management of MCI, but various professional organizations, 
panels, and clinicians have published recommendations for the management of MCI [16, 18, 31, 54]. Even though these 
publications acknowledge the need for treatments to reduce the rate of conversion to dementia, few specific treatment 
guidelines are provided. Those that were provided included: providing information on maintaining a healthy lifestyle; 
prevention and management of modifiable risk factors for cognitive impairment; treatment of behavioral and psychiatric 
symptoms; cognitive training that includes the use of mnemonics, association strategies, and computer-assisted training 
programs; and lifestyle interventions such as exercise, intellectually-stimulating activities, and leisure activities/socializing. 
Recommendations to the field include the need for randomized controlled designs using large samples, particularly 
because of the heterogeneity of the MCI population, as well as use of both cognitive and functional outcome measures 
and adequate follow-up periods [31].
 
8) Our ME-CCT intervention is consistent with guideline recommendations, and our preliminary data support the 
Our proposed study is consistent with future directions suggested in recent 
ME-CCT intervention (see Preliminary Data). 
MCI literature as well as the President’s national plan to fight Alzheimer's disease, released in 2012. The plan aims to 
 
develop effective prevention and treatment approaches for Alzheimer’s disease and related dementias by 2025.
Consistent with these recommendations, our proposed study intends to conduct a multi-site RCT evaluating the efficacy of 
a cognitive rehabilitation therapy for individuals with MCI. Because we intend to include participants who meet criteria for 
each of the four subtypes of MCI, our cognitive training program will address a variety of areas of cognitive impairment 
including memory, attention, and executive functions. We also intend to recruit a large sample of participants in order to 
account for the expected heterogeneity of our sample and make findings more generalizable. A 3-month follow-up will be 
conducted in order to examine the long-term effect of our intervention. In addition to focusing on improving cognitive 
functioning, the ME-CCT intervention also addresses the healthy lifestyle strategies that are associated with reduced MCI 
and dementia risk. Finally, our program's efficacy will be determined by the use of multiple outcome measures that not only 
assess objective cognitive performance, but also functional capacity, subjective everyday functioning, neuropsychiatric 
symptom severity, and frequency of participation in protective activities including exercise and cognitively-stimulating 
activities.
 
9) Working toward a theoretical model and a theoretically driven evidence-based treatment for MCI. In our 
systematic review of cognitive rehabilitation therapies for MCI [1], we published the first theoretical model of MCI treatment 
and rehabilitation. In doing so, we aimed to guide the future development and evaluation of evidence-based treatments for 
MCI, including our own proposed intervention. In this model, MCI is viewed as an intermediate stage between normal 
cognition and dementia. Individuals with MCI may convert to dementia, return to normal cognition, or have persistent MCI 
that does not convert to dementia. The etiology of MCI and dementia are viewed as multi-factorial, and a range of risk and 
protective factors, including those in 
, contribute toward increased or decreased risk, respectively. In some 
Table 1
individuals, the cumulative and interactive impact of these factors on the brain results in the behavioral manifestation 
known as MCI, which is characterized by three types of symptoms: a) mild cognitive compromise (measured by objective 
neuropsychological tests), b) mild functional compromise (evaluated by measures of subjective cognitive complaints, 
everyday functioning, and functional capacity), and c) commonly associated neuropsychiatric symptoms (measured by 
neuropsychiatric symptom questionnaires). Based on this model, effective cognitive rehabilitation therapies for MCI would 
therefore directly address and reduce these three types of symptoms. A cognitive rehabilitation therapy may also indirectly 
reduce these symptoms by targeting modifiable risk and protective factors that are known to increase (depicted as arrows 

with plus signs) or decrease (depicted as arrows with negative signs) risk of MCI and dementia. This theoretical model 
serves as the conceptual framework for the design of our proposed ME-CCT intervention and clinical trial. ME-CCT is 
designed to target all three types of MCI symptoms – cognitive compromise, functional compromise, and neuropsychiatric 
symptoms – along with increasing modifiable protective factors associated with reduced risk of MCI and dementia. The ME-
CCT intervention is comprehensive and multi-modal and, thus, incorporates the following three elements to target these 
symptoms and protective factors:
1) Multi-Modal Compensatory Cognitive Training Techniques: Participants learn and practice compensatory 
attention, and executive functioning (i.e., organization, planning, and problem-
cognitive skills designed to improve memory, 
solving). 
 
Compensatory strategies include internal strategies (e.g., visual imagery, chunking or acronyms to compensate 
 
for memory difficulties, structured problem-solving and planning methods to compensate for executive dysfunction), 
 
external strategies (e.g., calendars and timers), and environmental strategies (e.g., setting up a quiet work space). 
Participants are given in-class activities and weekly home exercises so they can practice and implement compensatory 
cognitive skills in their daily lives. Home exercises are discussed at subsequent sessions so that participants can receive 
feedback and troubleshoot application of new skills to their specific real life problems and activities of daily living. Given 
this emphasis on everyday functioning, and because previous MCI studies [55, 56] and our own pilot data (see Preliminary
) suggest that cognitive training interventions can increase daily functioning in adults with cognitive impairments, 
Studies
our primary hypothesis is that ME-CCT will improve everyday functioning in individuals with MCI. Because previous MCI 
studies [40, 56, 57] and our own pilot data (see 
) also suggest that comprehensive multi-modal 
Preliminary Studies
cognitive interventions can improve objective cognitive performance in adults with cognitive impairments, we additionally 
hypothesize that ME-CCT will improve objective functional capacity and cognitive performance in adults with MCI.
2) Psychotherapeutic Techniques: Given the high rates of neuropsychiatric symptoms (e.g., depression, anxiety, 
fatigue, and sleep problems) among individuals with MCI and the likelihood that these symptoms exacerbate problems 
with cognition and everyday functioning, our ME-CCT intervention incorporates mindfulness-based stress reduction 
exercises, fatigue and energy management skills, and sleep hygiene skills. In particular, our intervention includes weekly 
in-class practice of tension reduction exercises such as abdominal breathing and mindfulness meditation, as well as an 
education module that utilizes brief motivational interviewing techniques [58, 59] to enhance participants’ motivation to 
regularly practice mindfulness-based stress reduction exercises. In a systematic review of the benefits of mindfulness-
based stress reduction techniques, empirically supported benefits included reduced stress, depression, anxiety and 
worrying; improved sleep; and improved cognition, including improved attention, working memory, problem-solving, mental 
flexibility, and processing speed [60].
3) Lifestyle Techniques: Epidemiological and cross-sectional studies indicate that adults who frequently engage 
in physical activity (i.e., exercise) and cognitively-stimulating activities (e.g., puzzles, games, reading, social and cultural 
activities) are at significantly reduced risk for MCI and dementia [51, 61-64]. Moreover, we found in our systematic review 
of MCI treatments [1] that all 7 RCTs testing interventions to increase physical activity or cognitively-stimulating activities 
found significant improvements in objective cognitive performance relative to control conditions. Our ME-CCT intervention 
provides participants with education about the benefits of reducing modifiable risk factors (i.e., smoking and heavy alcohol 
use) and increasing modifiable protective factors (i.e., physical activity, cognitively-stimulating activity, and a healthy
/Mediterranean diet) known to be associated with MCI (
). We additionally incorporate education modules that 
Table 1
utilize brief motivational interviewing techniques [58, 59] to enhance participants’ motivation to increase the frequency of 
physical activity and cognitively-stimulating activities in their daily life; evidence suggests that motivational interviewing can 
effectively promote healthy lifestyle changes in adults with a range of conditions [58, 59, 65, 66].
 
10) Relationship to competing local or national clinical trials. A search of the national clinical trials registry [67] 
several trials are underway that evaluate cognitive rehabilitation interventions for MCI. Several of these trials 
reveals that 
evaluate single modality (i.e., non-comprehensive) memory or attention training techniques for MCI, which are not likely to 
have as robust of effects as comprehensive multi-modal interventions such as ME-CCT. Additional trials entail highly 
intensive (e.g., > 100 hours) and therefore expensive interventions for MCI, which are not likely to be feasible for broad 
numbers of Veterans across typical VA facilities nationally. However, to our knowledge, there are no competing national or 
local trials underway which specifically evaluate manualized, brief and inexpensive, yet comprehensive multi-modal 
cognitive rehabilitation interventions for older Veterans with MCI.
 
. The number of older Veterans with MCI seeking 
11) Relevance of the proposed work to the VA Patient Care Mission
treatment is increasing and is expected to increase more rapidly as Vietnam Veterans and the Baby Boomer population 
age. The cognitive effects of MCI and subsequent neurodegenerative disorders can adversely affect Veterans’ abilities to 
function independently. The VA currently spends over $19,000 annually per patient to care for Veterans with dementia 
[68], and delaying the onset of dementia even by one to two years will result in QOL gains for Veterans and substantial 
financial savings to the VA. Treatments that work are urgently needed. Therefore, an evidence-based cognitive training 
intervention that optimally addresses the complex needs of older Veterans with MCI is of critical importance to the VA 
patient care mission. To our knowledge, no RCTs have been conducted to evaluate the efficacy of manualized 
comprehensive compensatory cognitive training with older Veterans with MCI. Demonstrating that a new treatment for MCI 
is effective in improving cognition and functioning would be a significant contribution to the quality of care provided by the 
VA. If the treatment is found to be effective, the ME-CCT manual could be quickly disseminated to all VA facilities. With the 
program’s portability and ready availability, it will immediately be possible to deliver cost-effective, evidence-based 
compensatory cognitive training to Veterans with MCI.
 
 - Design and Methods
Section 9
Describe the research design and the procedures to be used to accomplish the specific aims of the 
9) 

project.  Provide a precise description of the planned data collection, analysis and 
interpretation.  Address sample size, inclusion of women and minorities.  Define in clear terms exactly 
what will be done to the human subjects.
The planned RCT uses a 2 (ME-CCT vs. SC) x 4 (Weeks 0, 4, 8 and 21) mixed effects experimental design. A 
Overview. 
total of 216 older participants with MCI will be recruited from the two participating sites, VASDHS and VAPORHCS (108 
from each site). By including two geographically distinct sites, we will not only enhance the efficiency of our recruitment 
and diversity of our sample, but also demonstrate the efficacy of ME-CCT at different geographic areas with different 
providers. Participants will be randomized to either the ME-CCT or SC group. Participants in the CCT group will receive 
our ME-CCT intervention during the first 8 weeks of participation in the study, whereas SC participants will receive a robust 
control intervention, Goal-Focused Supportive Contact. During study participation, all participants will continue to receive 
their usual medical, psychiatric and psychotherapeutic care. Both groups will undergo study evaluations at baseline, 4 
weeks (midway through ME-CCT), 8 weeks (immediately following ME-CCT completion) and 21 weeks (3 months after ME-
CCT completion).
 
: 1) Veterans 55 years old enrolled at one of the participating VA 
Participants and eligibility criteria. Inclusion Criteria
>
sites (VASDHS and VAPORHCS) who are able to provide informed consent. 2) Independently living. 3) Meet criteria for 
MCI based on previously published criteria [9, 16]. 4) Willingness to participate in audio-recorded sessions. Exclusion 
: 1) Current substance use disorder with < 30 days abstinence. 2) History of schizophrenia, schizoaffective 
Criteria
disorder, or other primary psychotic disorder. 3) History of significant brain injury with loss of consciousness > 30 minutes. 
4) Auditory or visual impairments that would prevent ability to participate in the cognitive rehabilitation group or benefit 
from compensatory strategies. MCI Criteria: Criteria for MCI will be based on previously published criteria [9, 16]: 1) 
Concern about a decline in cognitive functioning expressed by a physician, informant, participant or nurse. 2) Cognitive 
impairment in one or more of the following domains: executive function, memory, attention, language or visuospatial 
To determine 
abilities. 3) Normal or minimal impairment in functional activities. 4) Does not meet criteria for dementia. 
whether individuals meet criteria for MCI, two neuropsychologists (Drs. Twamley, Huckans, Jak, or Storzbach) will 
separately review each individual’s neuropsychological performance on a comprehensive neuropsychological battery (see 
) to determine study eligibility and classify MCI subtypes. If there are discrepancies, a third neuropsychologist will 
Table 6
review the data and the participant will only be included if consensus can be reached. The standard clinical 
neuropsychological assessment batteries conducted with adults with MCI through the Neuropsychology Clinics at the 
VASDHS and VAPORHCS sites are typically much longer (often exceeding three hours), and adults with MCI tolerate 
these batteries well. All subtypes of MCI will be included; however, in order to facilitate exploratory analyses to determine 
whether ME-CCT is more effective for particular subtypes, participants will be classified as follows, using previously 
published criteria [9, 16] and procedures similar to those we have used in our previous studies 
 A) 
[73]:
Single domain 
amnestic MCI will be operationally defined as performance on at least two memory measures falling 1 standard deviation 
>
(SD) below their age-appropriate norms. B) Single domain non-amnestic MCI will be operationally defined as performance 
on at least two measures in one domain of the above mentioned cognitive domains falling 1 SD below their age-
>
appropriate norms in the absence of memory impairment. C) Multiple domain amnestic MCI will be defined as meeting the 
above criteria for a memory deficit as well as meeting criteria for a deficit 1 SD below their age-appropriate norms on at 
>
least two measures within one or more of the additional cognitive domains (attention/processing speed, language, 
executive functioning). D) Multiple domain non-amnestic MCI will be operationally defined as performance on at least two 
measures in more than one of the above mentioned non-memory cognitive domains falling 1 SD or more below their age-
>
appropriate norms in the absence of memory impairment.
 
Total enrollment for the study will be 108 participants per site (54 ME-CCT and 
Recruitment and feasibility. 
54 SC per site), for a total of 216 participants (108 ME-CCT and 108 SC). Participants will be primarily 
recruited through clinic referrals and medical record review followed by recruitment letters sent to patients 
who meet the requisite pre-screening criteria. The recruitment letter will state that the individual may opt 
out by calling the research team indicating that they do not wish to be contacted, or they may indicate 
they are interested in learning more about the study by calling the study team. The letter will state that if 
the individual has not responded to the letter within two weeks, research personnel will contact them by 
phone. Participants will also be recruited through other research study referrals and contacted by letter
/phone (see Section 11: Recruitment for more recruitment methods).  We will recruit a sample composed of at 
least 25% of individuals from ethnic/racial minority groups, including African Americans, consistent with the 2013 US 
Census. This will provide us with enough subjects to explore minority status as a moderator of treatment outcome, 
although we do not expect differential effects. By having two sites, we will be better able to ensure adequate ethnic/racial 
diversity in our sample. We will recruit women and men. At the VASDHS, over the past year approximately one third of the 
500+ total referrals to the Neuropsychological Assessment Unit were diagnosed with MCI and likely would have been 
eligible for the proposed study. At VAPORHCS, 2,472 Veterans with a diagnosis of MCI were treated over the past two 
years; moreover, within the past year, of the 336 neuropsychological assessments conducted through the VAPORHCS 
Neuropsychology Clinic, 129 of those (59%) resulted in a diagnosis of MCI and likely would have been eligible to 
participate in the proposed study. At the VAPORHCS, since January 2015, 125 patients have been referred for the waiting 
list for the ME-CCT intervention; all referrals came from clinicians who had heard about the groups through word of mouth. 
We did not implement any intensive research recruitment efforts such as those proposed in this study (e.g., 
advertisements, letters to eligible patients, study compensation, study coordinators with protected time to seek out 
referrals). This demonstrates not only recruitment feasibility but also genuine interest in the groups, both by patients and 
the clinicians who refer them. Based on these data, we estimate that over 250 adults per year will be eligible to participate 
in the proposed study between the two sites, indicating that the goal of recruiting 216 participants over the course of the 
five-year study is very feasible. Nevertheless, should our VA recruitment efforts prove less successful than we anticipate, 

we will recruit additional participants from the academic institutions affiliated with each participating VA, namely University 
of California, San Diego (UCSD) and Oregon Health & Science University (OHSU), where Drs. Twamley and Huckans 
have joint appointments, respectively. UCSD programs that can refer participants include Senior Behavioral Health and the 
Memory and Resilience Center (see letter of support from Dr. Daniel Sewell, Medical Director and Co-Director of these two 
outpatient programs). At UCSD, the Senior Behavioral Health Program and the Memory, Aging, and Resilience Center 
evaluate and treat about 75 patients per year with MCI. OHSU programs that can refer participants include the National 
Institute on Aging (NIA)-funded Layton Aging & Alzheimer’s Disease Center (Directed by Co-Investigator Kaye) and the 
OHSU Division of General Internal Medicine and Geriatrics (Directed by Co-Investigator Eckstrom) (see letters of support 
from Drs. Kaye and Eckstrom). At OHSU, the Layton Center longitudinally follows about 450 research volunteers at risk for 
MCI or dementia, and enrolls 60 new volunteers per year.
 
We had a relatively low non-completer rate (11%) among subjects enrolled in our funded 
Retention and reimbursement. 
CCT study with OEF/OIF Veterans with mild TBI; moreover, all of the non-completers dropped out prior to the start of the 
group, while those who attended the first session of the group completed the 10-week CCT intervention. The five ME-CCT 
for MCI groups that we have run at VAPORHCS have had a similar drop-out rate of ~10%. We have, therefore, 
conservatively assumed a 20% drop-out rate and will recruit 216 participants to yield a final sample size of 180. Our power 
analyses were calculated assuming 20% attrition, yielding a total final sample of n=180 (see power analyses for each 
e will use subject compensation and reminder phone calls to reduce our attrition rate. Participants will be 
hypothesis). W
compensated $50 after each of the first three assessments, and $75 after the fourth and final follow-up assessment. If 
participants complete all four assessments, their total compensation will be $225. VASDHS participants who elect to use 
the Fitbit during the study will be able to keep the Fitbit device at the conclusion of their study participation.
 ME-CCT was developed, authored, and piloted by the PIs, Drs. Twamley and 
Experimental intervention (ME-CCT).
Huckans (see 
). ME-CCT is a manualized group-based behavioral intervention (8 weeks, 2 hours per week, 
Pilot Study 1
16 hours total) designed to improve cognitive and everyday functioning in patients with MCI. See 
 for a description 
Table 2
of the ME-CCT intervention and 
 for the treatment manual.
Appendix 6
We propose to use a robust control condition, Goal-focused Supportive Contact (SC), a group 
Control intervention (SC). 
therapy intervention that provides the same frequency and amount of therapist and other group member contact as ME-
CCT, but does not provide training in cognitive strategies, lifestyle strategies, or motivational enhancement. The SC 
intervention will have a primary focus on setting and achieving short or long-term goals. Focusing on goals is intended to 
provide “face validity” to potential participants and to enhance treatment attendance and reduce drop-out in this population. 
Sessions will be semi-structured and consist of check-in about the week prior, current symptoms or concerns, followed by 
a flexible discussion about setting and working toward goals. Sessions will typically include components of empathy and 
non-directive reinforcement of health, coping, and symptom management behaviors that grow out of group discussions, 
with only minimal therapist guidance. Participants will be asked to think about how the discussions had bearing on their 
individual goals, and will be encouraged to ask for the advice of other participants in achieving specific goals, but no 
specific training will be provided. Study therapists will not provide advice on reaching goals, but will encourage feedback 
from other group members. The SC control condition is being used in one of Dr. Twamley’s currently-funded cognitive 
training studies (NIMH R34) and has been used in published studies by her colleague, Dr. Granholm [6, 7].
Potential subjects will be identified through the specific recruitment
methods described in the 
 
Procedures.
 
below section 11.  Prior to enrollment, interested Veterans will be 
Study personnel will 
pre-screened. 
conduct a medical record review, including neuropsychological assessment records, to ensure study 
eligibility. As described in the following sections related to recruitment (Section 9: “Recruitment and 
Feasibility” and Section 11: “Recruitment”), study personnel will then contact individuals by phone or 
letter, depending on the specific recruitment method, to answer questions about the study, confirm 
interest in participation, and to schedule an initial study visit.  All eligible participants will then complete an 
which will include 
 and 
 (see 
); all 
 
initial study visit
informed consent
baseline measures
Table 5
participants will be carefully screened to ensure their ability to comprehend study procedures, risks and 
benefits. Participants at the VASDHS site will be offered the opportunity to use a Fitbit to track their physical activity and 
sleep during the study. (The Fitbit Charge 2 is a non-invasive, water-resistant, wrist-worn device that measures steps 
Upon enrollment, we will create a unique login 
taken, distance traveled, heart rate, and sleep quality and stages.) 
ID and password for each participant to enable us to track their data on the Fitbit website each week of 
the 8-week intervention; we will upload these data during the weekly group session. When connected to a 
compatible device (i.e., study computer), data are automatically uploaded to the users' Fitbit accounts. 
The researchers will bring a study laptop to the groups each week, at which time the researchers will 
upload participants' data for adherence and assessment purposes. These data will then be “dumped” into 
and stored on a secure study server. We will also upload their data during their last assessment at 21 
weeks; however, participants will be given the option of coming to the VA between the 8 week and 21 
week assessment to upload their data so they can get continued summary of their progress each week. 
The participants will be allowed to keep the device when the study ends and guided through the procedure 
for establishing a new username and password, thereby terminating the research staff's access to their 
account. All eligible participants will then be 
 to either the ME-CCT or SC group. Randomization tables will 
randomized
be prepared by Dr. Golshan, the study statistician, at the beginning of the study. For each site, groups will be randomly 
assigned to ME-CCT or SC based on the site’s randomization table. New study participants will be allocated to the current 
group awaiting randomization. Once group membership reaches the minimum of 6, the group will be randomized by Dr. 
Golshan, who will be blind to membership of each group. Randomization procedures and enrollment for each site will be 
monitored by Dr. Golshan, and if imbalance occurs at any site, he will recommend the necessary adjustment. Following 
randomization, participants will receive the 
 for 8 weeks. To reduce the risk of treatment 
intervention (ME-CCT or SC)

contamination, groups will be held at times and locations where Veterans in different groups will not have the opportunity 
to meet in a waiting room. We will also ask Veterans not to discuss their treatment with other Veterans until after 
completion of the protocol. Both groups will complete 
 (see 
) at baseline, 4 weeks (midway 
outcome measures
Table 5
through ME-CCT), 8 weeks (immediately following ME-CCT), and at 21 weeks (3 months after ME-CCT is completed); 
assessors will be blind to randomization status. None of the study procedures are part of standard care. Both groups are 
experimental.
 All assessment and intervention 
COVID Procedures: Assessments and group intervention sessions:
 
procedures will be completed using social distancing whenever possible, and requiring medical-grade 
procedure masks at all times. *Study has required follow up visits, but if restrictions were re-imposed, we 
would instead gather the information by phone or home-based video telemedicine so subjects would not 
need to return to the VA. We cannot do baseline assessments remotely, but if need be, we can collect 
partial follow-up data remotely. 
Attendance of each participant at each session will be recorded. Individual make-up sessions will 
Treatment Adherence. 
be offered to participants who miss a session, and attendance at make-ups will be recorded.
Treatment Fidelity. In addition to extensive therapist training and weekly supervision to ensure treatment fidelity, 
treatment fidelity will be closely monitored by Drs. Twamley and Huckans, using procedures similar to those used in our 
CCT for TBI study. ME-CCT sessions will be audio-recorded with an Olympus digital voice recorder (VN-4100PC or 
similar), and 20% of sessions randomly selected by Dr. Golshan will be rated by Drs. Twamley or Huckans using the ME-
CCT fidelity monitoring tool (see 
). Scores < 90% will trigger a review and plan for improving fidelity. SC 
Appendix 7
sessions will also be audiotaped and 20% of sessions randomly selected by Dr. Golshan will be rated by Drs. Twamley or 
Huckans using the ME-CCT fidelity monitoring tool to ensure that no ME-CCT content is present in SC sessions. Scores > 
 
0% will trigger a review and plan for improving fidelity. Specific plans have been developed for responding to sub-threshold 
adherence, ranging from extra training to statistically controlling for adherence to replacing therapists (in the extreme).
 Participants will complete the assessment battery at weeks 0, 4, 8 and 21, consisting of self-
Assessment Methodology.
report questionnaires and performance-based tests of cognition and functioning. Performance-based tests will not be 
administered at week 4, however, to avoid practice effects. Collateral informants (e.g., spouse, adult child, relative), when 
available, will complete questionnaires at weeks 0, 4, 8, and 21. Study measures and the rationale for including them are 
listed in 
. Measures will take < 3.5 hours to complete at week 0 (baseline), < 1 hour at week 5, and approximately 3 
Table 5
hours at weeks 8 and 21 (follow up). We have selected measures based on 4 criteria: 1) importance for assessing 
constructs evaluated in our aims, 2) brevity (to reduce subject burden), 3) reliability, and 4) demonstrated validity. The 
rationale for including each study measure is listed in 
 and further described below. Data collected at the second 
Table 5
site, VAPORHCS, will be transferred to VASDHS via drive behind the VA firewall, as we have done in a previous study. 
Fitbit data will be collected at the VASDHS site only.
Fitbit Charge 2 (https://www.fitbit.com/charge2): This non-invasive, water resistant device, which is worn 
around the wrist, will be used to measure participants’ activity levels, heart rate, and sleep quality. The 
Fitbit uses a three-dimensional accelerometer to sense movement. It measures steps taken, distance 
walked, calories burned, active/inactive minutes, stationary time, heart rate, hours and quality of sleep, as 
well as stages of sleep. The Fitbit’s measurement of self-paced and prescribed intensity exercise has been 
validated against the Omron HJ-720IT accelerometer and direct observation.
 
Table 5. Study Measures
Measure
Purpose
/Specific Aim:
Hypothesis
Construct Assessed
Weeks 
Administ
ered
Ti
m
e 
(m
in)
Patient Health Questionnaire-
9 (PHQ-9) [74].
Subject 
characterization; 
Exploratory Aim 
4.
Depression symptom severity.
0
2
General Anxiety Disorder-7 
Scale (GAD-7) [75].
Subject 
characterization; 
Exploratory Aim 
4.
Anxiety symptom severity.
0
2
PTSD Checklist (PCL)
Subject 
characterization; 
Exploratory Aim 
4.
PTSD symptom severity.
0
2
Wide Range Achievement 
Test-4-Reading (WRAT-4) 
[76].
Subject 
characterization; 
Exploratory Aim 
4.
Reading ability (premorbid IQ estimate).
0
5

Neurocognitive Composite 
Score
(Average z Score of tests in Ta
targeted by ME-CCT).
ble 6 
Aim 1: H1 (co-
primary outcome).
 
Neurocognitive functioning (see cognitive 
domains in 
targeted by ME-CCT).
Table 6 
0, 8, 21
90
Functional Capacity 
Composite Score (Average z 
Score of tests in 
).
Table 7
Aim 1: H1 (co-
primary outcome).
Functional capacity (i.e., performance 
based measures of everyday functioning; 
see 
).
Table 7
0, 8, 21
45
Subjective Everyday 
Functioning Composite Score 
(Average total score across 
two Neuro-QOL scales, 
Applied Cognition Executive 
Function and Applied 
Cognition General Concerns 
[77]).
Aim 2: H2 
(secondary 
outcome).
Subjective cognitive complaints and 
everyday functioning.
0, 4, 8, 21
5
Everyday Cognition Scale 
(ECog) [78].
Aim 2: H2 
(secondary 
outcome).
Collateral measure of cognitive and 
everyday functioning.
0, 4, 8, 21
10
Cognitive Activity Inventory 
[63, 79].
Aim 3: H3; 
Exploratory Aim 
4.
Recent frequency of engagement in 
activities requiring mental exercise, a 
protective factor known to reduce risk of 
MCI and dementia.
0, 4, 8, 21
3
CHAMPS Physical Activity 
Questionnaire for Older Adults 
[80].
Aim 3: H3; 
Exploratory Aim 
4.
Recent frequency of engagement in 
activities requiring physical exercise, a 
protective factor known to reduce risk of 
MCI and dementia.
0, 4, 8, 21
6
Portland Cognitive Strategies 
Scale (PCSS) [69].
Exploratory Aim 
4.
Recent frequency of use of cognitive 
strategies taught in the ME-CCT class.
0, 4, 8, 21
5
 
Additional Measures Added to the Study or Required by eScreening: 
Motivation/Efficacy items -- added to the study to track participant motivation for lifestyle changes 
addressed in the intervention. These are the same items that are used in the ME-CCT intervention. 
Example item: On a scale of 0-10, based on your current life and goals, how confident are you that, if 
you decided to exercise more regularly than you do now, you could do it? (rated 0-10)
Measures Required by eScreening: basic demographics and military history, Basic Pain, PROMIS Pain 
Intensity and Interference, Alcohol Use Disorders Identification Test-C, Insomnia Severity Index, Brief 
TBI Screen, Patient Health Questionnaire 15, and WHO Disability Assessment Schedule-2. All are brief, 
standard measures required by eScreening. They are brief enough to not increase subject burden 
significantly.
. 
 will be a composite z score derived by averaging 
Co-Primary Outcomes (Aim 1: H1) Objective cognitive performance
the scores across tests in our battery (see 
) except for language measures, which are only used in the diagnostic 
Table 6
evaluation. ME-CCT teaches strategies that participants can use to improve their performance on real-world tasks as well 
as traditional objective neuropsychological tests. The neurocognitive battery was also designed to confirm accurate 
diagnosis of MCI using published [9, 16] criteria and therefore confirm eligibility criteria. When possible, we have selected 
measures with equivalent forms which will be alternated to reduce practice effects. We found significant CCT-associated 
improvements on several of these measures, namely WAIS-IV Digit Span, HVLT-R, and D-KEFS Verbal Fluency, following 
CCT for TBI (see 
). 
 will be a co-primary outcome, 
Pilot Study 2
Objective, performance-based functional capacity
measured with a battery of performance-based (role play) measures (see 
) that ask participants to apply everyday 
Table 7
living skills on tasks that are highly congruent with analogous real-world activities (e.g., medication management, financial 
skills). Performance-based tests of everyday living skills are the most objective way to capture improvements in functional 
abilities. We will use a composite z score derived by averaging scores across tests in the battery. We found near-
significant (p=.059) improvements on one of these measures, the UPSA, following CCT for TBI (see 
).
Pilot Study 2
 Subjective cognitive complaints and subjective everyday functioning will be a composite 
Secondary Outcomes (Aim 2: H2).
score derived by averaging the total scores across two Neuro-QOL scales, the Applied Cognition Executive Functions 
Scale and the Applied Cognition General Concerns Scale [77]. The Neuro-QOL scales were developed as part of the NIH 
Measurement Initiative to promote aggregation and cross-comparability of results across studies nationally, and they are 
specifically designed for use in clinical trials for the evaluation of interventions for neurological conditions [77]. Neuro-QOL 
measures are brief (8-items), psychometrically robust, and highly patient-centered in that they are sensitive to the 
symptoms, concerns and issues that neurological patients most commonly report and deem relevant to their well-being. 
We found significant improvements on these Neuro-QOL scales following ME-CCT for MCI in our pilot study (see Pilot 
). We also found significant improvements on two other measures of cognitive complaints and everyday 
Study 1
functioning following CCT for TBI (see 
). We will also include the ECog, a collateral (e.g., spouse, close 
Pilot Study 2
relative) measure of cognitive and everyday functioning [78]. The ECog has demonstrated sensitivity to detecting varying 
levels of impairment across clinical groups and can differentiate between the four subtypes of MCI [78]. We found 
significant improvements on the ECog in adults with MCI following the CogSMART intervention in our pilot study (see Pilot 
). We will focus analyses on the general factor (i.e., single summary score) derived from the ECog.
Study 3

Table 6. Neurocognitive Battery
Domain
Test
Description
Memory (targeted 
in ME-CCT)
 
 
Hopkins Verbal Learning Test-
Revised (HVLT-R) [81]
Brief Visuospatial Memory Test-
Revised (BVMT-R) [82]
Oral list-learning task requiring acquisition of a list of 12 
words from 3 categories over 3 trials.
A test that involves learning and reproducing six geometric 
figures from memory.
Attention (targeted 
in ME-CCT)
 
Wechsler Adult Intelligence 
Scale, Fourth Edition (WAIS-IV) 
Digit Span [83]
WAIS-IV Coding [83]
Delis-Kaplan Executive 
Function System (D-KEFS) 
Trails, Number and Letter 
Sequencing [84]
Participant recalls sequences of numbers in the same order 
(Digits Forward), in reverse order (Digits Backwards), and in 
ascending order (Digit Span Sequencing).
Participant uses a key to draw symbols corresponding to 
numbers.
Participant quickly draws a line connecting numbers in order 
(Number Sequencing) and then letters in order (Letter 
Sequencing).
Executive Function 
(targeted in ME-
CCT)
 
D-KEFS Trails, Number-Letter 
Switching [84]
D-KEFS Color-Word 
Interference Test, Inhibition and 
Inhibition-Switching [84]
 
NAB Categories [88]
Participant switches back and forth between connecting 
letters and numbers in order (i.e., 1, A, 2, B, 3, C, etc.)
A Stroop task in which participants name the color words 
are printed in rather than reading the color word (Inhibition), 
and then switches between naming the color or reading the 
word (Inhibition-Switching).
ask
An ecologically valid measure in which the participant is 
ed to generate as many different two-group 
categories as they can based on photographs and 
verbal information.
Language (needed 
for diagnostic 
evaluation, but not 
targeted in ME-
CCT or included in 
composite z score)
Boston Naming Test [85]
D-KEFS Verbal Fluency [84]
Participant names pictures of familiar objects.
Participant names animals for 1 minute (Category Fluency), 
and then words that start with a particular letter for 1 minute 
(Letter Fluency).
 
Table 7. Performance Based Functional Capacity Battery
Domain
Test
Description
Communication 
and financial 
management skills
UCSD Performance-Based 
Skills Assessment-Brief (UPSA-
B) [86]
A role-play-based test that measures ability to communicate 
efficiently and accurately and apply financial skills to simple 
(counting change) and more complex (paying a bill by 
check) situations.
Medication 
management skills
Medication Management Ability 
Assessment (MMAA) [87]
A performance-based measure of ability to manage a 
simulated, complex medication regimen similar in complexity 
to one that an older person is likely to be prescribed.
Memory skills 
relevant to 
everyday 
functioning
NAB Daily Living Memory [88]
An ecologically valid measure in which the participant is 
asked to recall, both immediately and following a delay, 
information encountered in daily life, including medication 
instructions and a name, address and phone number.
Problem-solving 
skills relevant to 
everyday 
functioning
NAB Judgment [88]
An ecologically valid measure in which the participant is 
asked to respond to questions about how they would 
address various everyday problems related to home safety, 
health and medical issues.
Driving/attention 
skills
NAB Driving Scenes [88]
An ecologically valid measure in which the participant is 
asked to attend to and identify changes across simulated 
driving scene relevant to driving safety.
 
. ME-CCT uses motivational interviewing techniques designed to increase participant 
Additional Outcomes (Aim 3: H3)
engagement in healthy lifestyle behaviors known to reduce risk for dementia, namely physical exercise and mental 
exercise [1, 51]. Increased participation in these modifiable protective factors will be evaluated using physical and 
cognitive activity inventories. The CHAMPS Physical Activity Questionnaire for Older Adults has previously demonstrated 
adequate short-term stability and construct validity in older adults, and is sensitive to changes in physical activity [80]. The 
Cognitive Activity Inventory (Current Cognitive Activity Subscale) has demonstrated adequate short term temporal stability, 
internal consistency and validity in older adults [79], and higher scores on this measure are associated with reduced risk 
for cognitive decline in healthy older adults and for developing MCI and Alzheimer’s disease [62-64].
. As a preliminary evaluation of mechanism, we will conduct exploratory analyses to 
Mediators (Exploratory Analyses)
determine if increased use of the compensatory cognitive strategies taught through the intervention mediates 

improvements in objective cognitive performance and functional capacity. The frequency with which participants use these 
strategies will be evaluated with the Portland Cognitive Strategies Scale (PCSS) [69]. Our pilot data demonstrate 
significant increases in cognitive strategy use on the PCSS in Veterans with MCI following ME-CCT (see 
). 
Pilot Study 1
We also found significantly increased strategy use on the PCSS in combat Veterans following CCT for TBI (see Pilot 
). Using the CHAMPS Physical Activity Questionnaire, the Fitbit data, and the Cognitive Activity Inventory, we will 
Study 2
also evaluate whether increases in physical activity and mental activity mediate improvements in objective cognitive 
performance and functional capacity.
 Baseline measures were selected to ensure that 
Baseline Characterization and Moderators (Exploratory Analyses).
baseline rates of demographics, medical conditions, BMI, medication and substance use, psychiatric disorders, premorbid 
IQ, and significant other involvement are equivalent across groups. If between group analyses reveal any differences 
across groups in terms of these factors, they will be controlled for in subsequent analyses. In order to preliminarily explore 
for whom this intervention is most effective, we will evaluate whether these baseline variables (see 
) or baseline 
Table 5
performance on primary and secondary endpoint measures moderate ME-CCT associated improvements in objective 
cognitive performance and functional capacity.
HYPOTHESIS-SPECIFIC DATA ANALYSIS PLAN AND POWER ANALYSES
Data analyses will proceed in stages: 1) First, descriptive statistics and exploratory analyses will be used to assess the 
normality of the data and homogeneity of variance. The continuous outcome data will be transformed if necessary by using 
an appropriate transformation such as the log transform for skewed long tailed data. Similarly, potential covariates will be 
summarized with descriptive statistics and graphs to determine the most appropriate way to treat these variables. In 
addition, the results will be inspected for bias due to dropouts or missing data. 2) Although we don’t anticipate any baseline 
differences, we will compare any differences among groups and sites on baseline measures. Any statistically and clinically 
significant differences will be controlled for in subsequent analyses by adding the target variables as covariates to the 
model. 3) We propose to use mixed effects modeling to account for clustering structure of the data (i.e., repeated 
assessments within an individual, groups, therapists and sites) for main hypotheses testing. The mixed effects approach is 
more powerful than traditional methods and allows the inclusion of subjects with missing data or those who were 
terminated early in the study, without relying on data imputation procedures. Two specific forms of the mixed effects 
models of random regression models (RRM), also known as hierarchical linear models (HLM) or multilevel models, and 
mixed model analysis of variance (MMANOVA) will be considered. Each outcome variable will be graphed versus time for 
each subject to evaluate what function of time best describes the data. If the change is linear we will proceed with the HLM 
structure. If the time pattern is not immediately apparent we will proceed with the MMANOVA. 4) We will use the extension 
of the Pattern-Mixture models [89] which allow subject-to-subject heterogeneity, to assess if there is bias due to drop out 
or missing data. Furthermore, the randomness of missing data will be examined according to recommended procedures 
[90], which includes comparing group differences in the primary outcomes of subjects with versus without missing data. 
Specific plans for testing each hypothesis are below.
 
H1: Compared to those in SC, participants in ME-CCT will show significant improvements in objective cognitive 
performance and functional capacity.
 Neurocognitive composite score (Average z score across subtests in the Neurocognitive Battery 
Dependent variables:
detailed in 
); Functional capacity composite score (Average z score across subtests in the Functional Capacity 
Table 6
Battery detailed in 
). 
 Treatment group (2 levels, ME-CCT and SC), and Time (4 levels, 
Table 7
Independent variables:
Weeks 0, 4, 8, 21). 
 We will analyze data on all randomized subjects for whom we have a baseline 
Statistical Analysis:
assessment and at least one post-baseline evaluation. Data will be analyzed by mixed effects model methods [91-93] for 
 
linear or non-linear trends based on earlier inspection of data. The mixed effects model method provides an estimate of 
the individual variability around the population trend, the variability of the individual intercepts (baseline values) and slopes 
 A fully saturated treatment X time model will be utilized for 
(changes across time), and the correlation between them.
inference. Covariance structure will be chosen based on Akaike’s Information Criterion (AIC). Random group level 
treatment effects will also be evaluated for importance based on the model AIC. Denominator degrees of freedom will be 
calculated using the Kenward-Roger small sample correction. The effects of site, therapist and their interaction with 
treatment will be included and tested. However, we do not anticipate any significant interactions or main effects of these 
factors given our balanced study design (equal numbers at each site in each group), our standard training and operating 
procedures at both sites and with all therapists, and our previous analyses from our similarly-designed study (our CCT for 
TBI study). In any case, the analysis procedures will include these factors and their interaction effects to avoid allowing site 
or therapist effects to bias treatment comparisons. If we detect any imbalances between the treatment groups, we will 
follow the primary analyses above with subsequent analyses considering the imbalances to verify that the conclusions are 
Analyses will be conducted within and across nested levels of the study design; this will 
not affected by the imbalances. 
involve within-subject analyses (comparison of occasions of measurement nested within an individual), as well as between-
subject analyses. In addition, any treatment group comparison will be adjusted for subject-specific characteristics, and 
adjustments for changes in these characteristics over the course of the study can be incorporated into the single-subject 
analyses. 
 In addition to the p
Power Analysis:
rocedures described by Hedeker and colleagues [94] for Random 
the RMASS program provided by Hedeker), we used several standard other methods for power 
Regression Models (
calculation and estimation of needed sample size. We selected the sample size that would provide us with a minimum of 
80% power across all hypotheses and their expected effect sizes. We used this method with the following assumptions to 
estimate required sample size: the mixed design of two groups (ME-CCT and SC) and time (4 levels, weeks 0, 4, 8, 21) 
where the slope is the dependent measure; alpha-level of .02, nature of the hypothesis (two-sided), dropout rate (up to 
20%), autoregressive covariance structure (with correlation between sequential assessments set at .45) of the longitudinal 
data, medium effect size as a between-group difference increasing linearly from 0 at baseline to .5 SD units at the last time 
point, various correlations (.2, .5, and .8) between the repeated measures, and various effect sizes from medium to large. 
We estimated that with a final sample size of 180 participants (216, with a drop-out rate of 20%), the study will have 

minimum 85% power to yield a statistically significant result for a medium effect size. As is noted in the previous sections, 
we have found medium to large post-treatment effect sizes for several outcome measures in our previous studies.
 
H2: Compared to those in SC, participants in ME-CCT will show significant improvements on measures of 
subjective cognitive complaints, subjective functioning, and collateral measures of everyday functioning.
 Subjective Everyday Functioning Composite Score (average total score across the two Neuro-QOL 
Dependent variables:
scales, namely the Applied Cognition Executive Function Scale, and the Applied Cognition General Concern Scale); ECog. 
 Treatment group (2 levels, ME-CCT and SC), and Time (4 levels, Weeks 0, 4, 8, 21). 
Independent variables:
Statistical 
 Data will be analyzed similar to the method described for H1. 
 Power analyses were conducted 
Analyses:
Power Analyses:
similarly to H1, and the study will have 87% power to yield a statistically significant result for a medium effect size for H2. 
We have found large effects on subjective cognitive/functional complaints in previous studies.
 
H3: Compared to those in SC, participants in ME-CCT will show increased participation in protective activities, as 
measured by physical and cognitive activity inventories.
 Cognitive Activity Inventory, CHAMPS Physical Activity Inventory for Older Adults. 
Dependent variables:
Independent 
 Treatment group (2 levels, ME-CCT and SC), and Time (4 levels, Weeks 0, 4, 8, 21). 
 Data 
variables:
Statistical Analyses:
will be analyzed similar to the method described for H1. 
 Power analyses were conducted similarly to H1, 
Power Analyses:
except the alpha level was set at .01; the study will have 80% power to yield a statistically significant result for a medium 
effect size for each dependent measure evaluated through H3.
 
Exploratory Analyses. We will conduct exploratory analyses to evaluate whether increased use of compensatory 
cognitive strategies and increased physical and cognitive activity (PCSS, Cognitive Activity Inventory, CHAMPS Physical 
Activity Inventory for Older Adults, Fitbit data) mediate improvements in objective cognitive performance and functional 
capacity. Furthermore, we will explore for whom this intervention is most effective by evaluating whether baseline variables 
demographics, medications, and substance use measured through the clinical interview; premorbid IQ measured by 
(e.g., 
the WRAT-4; baseline health and psychiatric status measured through the clinical interview, PHQ-9, and GAD-7), baseline 
, or involvement of significant others in treatment will moderate 
performance on primary and secondary endpoint measures
ME-CCT-associated improvements in objective cognitive performance and functional capacity. 
 The 
Statistical Analyses:
effect of moderator and mediator variables will be examined following the procedures recommended by statistical experts 
Kraemer, Cohen and Cohen, and Busemeyer and Jones [95-97]. The effects of moderator and mediator variables will be 
explored using similar models as ones described in H1.
 
Questionnaires & Surveys
9.8 
Section 
Provide the name and a reference for questionnaires/surveys that are standard or identify them here 
9.8) 
and attach a copy of the questionnaire/survey.
Please see Tables 5, 6, and 7 of Section 9. All are standard measures.
 
 Data Safety Monitoring Board or Plan
9.9
Section 
Provide a Data Safety Monitoring Plan (DSMP) or the details of a Data Safety Monitoring Board.
9.9) 
Safety Monitoring will be performed by the study staff who conduct the interviews, administer the 
assessment questionnaires, conduct the psychological and cognitive assessments, and facilitate the group 
interventions. Any adverse events will be reported immediately to the PIs, who will examine the patient 
and determine if any additional evaluation or treatment is needed. The PIs will recommend termination of 
participation, provide appropriate referrals, and engage in follow-up if substantial decline in functioning is 
observed. Referrals will also be offered to non-responders and any participant who requests further 
treatment. The PIs will ensure that adverse events are properly reported to the IRB. Study personnel will 
examine all cumulative adverse events quarterly to determine if there are any systematic problems.
Data will be monitored for accuracy and integrity across the duration of the study. Study personnel at 
each site will be adequately trained by the respective PI to conduct screenings, medical record reviews, 
clinical interviews, standardized neuropsychological assessments, and the ME-CCT and SC interventions 
prior to engaging in any data collection. Study personnel will also have professional education and training 
as required to conduct the study assessments and interventions. A paper questionnaire will be used to 
guide medical record reviews to ensure that the same historical information is gathered and coded for all 
study participants. The self-report questionnaires, collateral informant measure, functional capacity 
battery, and neuropsychological battery all consist of standardized protocols with scripted questions and 
standard scoring systems that quantify answers. Fidelity to the ME-CCT treatment and SC group will be 
closely monitored by the PIs. All ME-CCT and SC sessions will be audio-recorded, and 20% of group 
sessions will be randomly selected by Dr. Golshan (the study’s biostatistician), and will be rated by Drs. 
Huckans or Twamley using the ME-CCT fidelity monitoring tool. Scores with <90% fidelity will trigger a 
review and a plan for improving fidelity.

With regard to safety and security of electronic data, multilevel data security programs have been written 
into the sites’ network operating systems to ensure that only authorized research personnel have access 
to the Center Network. Backups are conducted regularly, and an electronic archive of all data is kept 
offsite to ensure against loss by fire, theft, etc. All statistical transfer routines are inherently secure via 
operating platform and contain no patient names or personal data. A database will be developed using 
Microsoft Access by the study biostatistician. The database will be tested and the final version will be 
distributed to the participating study sites. Two study support persons located at each site will enter data 
from the hard copy forms into the database to ensure accuracy of data entry. All data entry discrepancies 
will be solved by the site study coordinator. Hard copy source documents will be kept and stored at the 
VA site location at which they were gathered. For adherence monitoring, digital audio-recordings of 
sessions will be kept. The recording will be de-identified, password-protected, and encrypted.
Upon enrollment, we will create a unique login ID (subject number to avoid entering identifiable 
information) and password for each participant to enable us to track their data on the Fitbit website each 
week of the 8-week intervention; we will upload these data during the weekly group session. When 
connected to a compatible device (i.e., study computer), data are automatically uploaded to the users' 
Fitbit accounts. The researchers will bring a study laptop to the groups each week, at which time the 
researchers will upload participants' data for adherence and assessment purposes. These data will then be 
“dumped” into and stored on a secure study server. We will also upload their data during their last 
assessment at 21 weeks; however, participants will be given the option of coming to the VA between the 
8 week and 21 week assessment to upload their data so they can get continued summary of their 
progress each week. The participants will be allowed to keep the device when the study ends and guided 
through the procedure for establishing a new username and password, thereby terminating the research 
staff's access to their account.
Every effort will be made to prevent missing data. Veterans who miss a group session will be encouraged 
to attend an individual make-up session. Attendance at all group and individual sessions will be recorded 
and this will be used as a covariate (if appropriate) in final analyses. Veterans will be given every 
opportunity to reschedule missed study assessment visits (i.e., baseline, week 4, week 8, week 21) and 
study personnel will closely monitor participants’ completion of all study elements. Reminder calls will be 
conducted prior to scheduled study visit appointments, to increase the likelihood of attendance. In the 
event of unavoidable missing data (including participant drop-out prior to completion of all study 
elements), the missing data will be handled in the data analysis stage. Specifically, the proposed mixed 
effects modeling approach is more powerful than traditional methods and allows for inclusion of subjects 
with missing data or those who were terminated early on in the study, without relying on data imputation 
techniques. The randomness of missing data will also be assessed, by comparing group differences on 
primary outcome variables for subjects with missing data and those without missing data. 
The VA Centralized Data Monitoring Committee will assist with data safety monitoring.
 
Pictures and Audio/Video Recordings of Patients
9.11 
Section 
Describe the purpose and of photographs (facial) or audio or video recordings of patients
9.11) 
Audio recordings are necessary for the purpose of assessing therapist fidelity to the intervention.
 
 - Human Subjects
Section 10
Describe the characteristics of the proposed subject population. Include age, gender, ethnicity, and 
10) 
health status as appropriate.  
 
 Provide inclusion and exclusion criteria as appropriate.  Indicate the 
 
number of VASDHS participants to be studied.  For multisite studies, also provide the total number of 
  
subjects from all sites.  Indicate the estimated number of 
 subjects that will fail the screening 
consented
process, if any.
Inclusion Criteria: 1) Veterans >55 years old enrolled at one of the participating VA sites (VASDHS and 
VAPORHCS) who are able to provide informed consent. 2) Independently living. 3) Meet criteria for MCI 
based on previously published criteria [9, 16]. 4) Willingness to participate in audio-recorded sessions. 
Exclusion Criteria: 1) Current substance use disorder with < 30 days abstinence. 2) History of 
schizophrenia, schizoaffective disorder, or other primary psychotic disorder. 3) History of significant brain 
injury with loss of consciousness > 30 minutes. 4) Auditory or visual impairments that would prevent 
ability to participate in the cognitive rehabilitation group or benefit from compensatory strategies. MCI 
Criteria: Criteria for MCI will be based on previously published criteria [9, 16]: 1) Concern about a decline 
in cognitive functioning expressed by a physician, informant, participant or nurse. 2) Cognitive 

impairment in one or more of the following domains: executive function, memory, attention, language or 
visuospatial abilities. 3) Normal or minimal impairment in functional activities. 4) Does not meet criteria 
for dementia. To determine whether individuals meet criteria for MCI, two neuropsychologists (Drs. 
Twamley, Huckans, Jak, or Storzbach) will separately review each individual’s neuropsychological 
performance on a comprehensive neuropsychological battery (see Table 6) to determine study eligibility 
and classify MCI subtypes. If there are discrepancies, a third neuropsychologist will review the data and 
the participant will only be included if consensus can be reached. The standard clinical neuropsychological 
assessment batteries conducted with adults with MCI through the Neuropsychology Clinics at the VASDHS 
and VAPORHCS sites are typically much longer (often exceeding three hours), and adults with MCI 
tolerate these batteries well. 
Total enrollment for the study will be 108 participants per site (54 ME-CCT and 54 SC per site), for a total 
of 216 participants (108 ME-CCT and 108 SC). 
We do not anticipate a large number of consented subjects that will fail to meet MCI criteria, because we 
expect most referrals to the study to come from the Neuropsychological Assessment Unit, which will have 
already determined a diagnosis of MCI.
 
Individuals with Cognitive/Decisional Impairment
10.5 
Section 
Provide the rationale and additional study procedures that will be required for including individuals 
10.5) 
with known cognitive impairment or institutionalized individuals.  (Address Decisional Capacity 
Assessment and Surrogate Consent Sections 12.5 and 12.6).
This is a study of people with known cognitive impairment -- MCI. Decisional capacity assessment will be 
used to ensure capacity to consent to the research.
 
 - Recruitment
Section 11
Describe the plans for recruitment of subjects (or selection of subjects as in record review). This 
11) 
description must include how, when, and where potential subjects are approached as well as procedures 
such as data mining, physician referral, etc. Include how selection is equitable.  Indicate if vulnerability 
to coercion may be present and if so plans to ensure voluntary participation.
Our primary recruitment method will be from clinic referrals and medical record review (see below for 
more details). In addition, participants will also be recruited through research study referrals (see below 
for more details). 
For eligible individuals identified by study staff through clinic referrals/medical record review, the study 
staff will send a recruitment letter (or contact by phone if the Veteran gave their verbal permission to 
being contacted by phone). The letter will state that the individual may opt out by calling the research 
team indicating that they do not wish to be contacted, or they may indicate they are interested in learning 
more about the study by calling the study team. The letter will state that if the individual has not 
responded to the letter within two weeks, research personnel will contact them by phone. Study Personnel 
will respond to calls from individuals who are interested in the study to answer any questions they might 
have about the study and to schedule an Initial Study Visit if they remain interested. If no response to the 
letter is received within two weeks, the research team will contact the individual by phone but with limited 
interaction. During this follow-up phone call, the researcher will identify themselves, explain why they are 
calling, and ask if the individual received the letter. If they did, the researcher will ask if they have 
reviewed the letter and whether or not they are interested in hearing more about the study. If the 
individual has received, but not reviewed, the letter, the researcher may ask if they are interested in 
hearing more about the study or receiving more information. After answering their questions, the 
researcher will schedule an Initial Study Visit for those who state they are interested in participating. If 
the Veteran has not received the letter, the researcher will only ask permission to send a second letter 
and confirm the individual’s address; no other information will be requested at that time. 
Individuals referred from other VA IRB-approved research studies (who gave their consent to be 
contacted about additional research opportunities), will also be sent a recruitment letter via mail prior to 
being contacted by phone, unless they have specifically consented to phone contact. If no response to the 
letter is received within two weeks, research personnel will follow the same follow-up phone call 
procedures as stated in the previous paragraph. Studies we will recruit from include protocol numbers: 
H170028, H160090, H140057, H130022, and H160022, and other applicable VA studies with older 
Veterans with MCI. 

For all individuals who express interest in the study, research staff will provide information about the 
study and its procedures via phone. For those individuals who remain interested, study staff will confirm 
their eligibility via phone before proceeding to schedule their baseline visit: consent and initial 
assessment. Individuals not interested in participating will not be contacted again.
 
Recruitment Materials
11.1 
Section 
Identify all recruitment materials (flyers, advertisements, letters, etc.) that will be used. The text 
11.1) 
of all communications with prospective participants must be reviewed and approved by the IRB before it 
can be used.  You will be reminded to attach copies of recruitment materials to the initial submission 
packet.
Recruitment letters and recruitment flyers. Research flyers will be given to other appropriate research 
studies that include Veterans with MCI, appropriate VA clinics, and VA medical providers, such as 
geropsychiatrists and neurologists, who may also be able to refer Veterans with MCI.
 
 - Informed Consent
Section 12
Indicate whether or not each category of consent is involved in this study:
12) 
 informed consent
12a) Signed
 Yes   
 No
12b) Signed consent for 
 (VA form 10-3203) [NO LONGER REQUIRED]
picture/voice recording
 Yes   
 No
Waiver of documented consent (e.g., 
consent)
12c) 
oral 
  Yes   
  No
12d) Request for a 
 of consent (i.e., a "full" waiver, not just for screening)
waiver
  Yes   
  No
 Alteration of 
 of consent.
12e)
other required elements
  Yes   
  No
12f) Child assent to participate (Director approval will be required)
  Yes   
  No
Will any language 
 be used by those obtaining consent and understood by the 
12g) 
other than English
prospective participant or the legally authorized representative?
  Yes   
  No
 to determine if participants have the capacity to consent for 
12h) Decisional Capacity Assessment
themselves.
 Yes   
 No
 consent (legally authorized representative)
12i) Surrogate
  Yes   
  No
 
Informed Consent Process
12.1 
Section 
Will consent be obtained before any study procedures are performed (including screening 
12.1a) 
procedures except screening procedures with Consent/HIPAA waiver approval)?

 Yes   
 No
Will the information being communicated to the participant or legally authorized representative 
12.1b) 
during the consent process include exculpatory language through which the participant or legally 
authorized representative is made to waive or appear to waive any of the participant’s legal rights or 
release or appear to release the Researcher, Sponsor, the VA or its agents from liability for negligence.
  Yes   
  No
A master list of all VA subjects consented (written or not) under this protocol number will be 
12.1c) 
maintained.  (If a waiver of the master list entry requirement is requested below and will be approved, 
.
indicate Agree)
 Agree 
 Disagree
Identify the circumstances under which consent will be obtained including where the process will 
12.1d) 
take place; any waiting period between describing the research and obtaining consent including sufficient 
time for the prospective participant to consider participation, and any steps taken to minimize the 
possibility of coercion or undue influence.
Written informed consent will be obtained in person by the PI, co-investigator Jak, or a trained member of 
the research staff, in a private office. Decisional capacity assessment will be administered to all individuals 
who express a desire to participate. Potential participants will be asked to confirm that all of their 
questions have been answered prior to providing consent. Any potential participant who would like to take 
the consent document home for further consideration will be invited to do so.
 
Decisional Capacity Assessment
12.6 
Section 
Describe the method(s) for determination of decisional capacity: 
12.6a) 
(see ? for guidance)
A post-consent questionnaire will be administered to ensure that individuals understand the purpose of 
the study, the study procedures, the potential risks, and the voluntary nature of research participation.
If subjects with limited decisional capacity will be enrolled, describe methods for obtaining 
12.6b) 
subject assent or why they are not indicated:
Individuals who cannot pass the decisional capacity assessment will not be enrolled.
If subjects with limited decisional capacity will be enrolled, describe procedures for respecting 
12.6c) 
subject dissent and any additional safeguards or why these features are not needed:
N/A
If subjects with limited decisional capacity will be enrolled, describe the risk and, if greater than 
12.6d) 
minimal, the relation to potential benefits:
N/A
If subjects with limited decisional capacity will be enrolled, describe the justification for the 
12.6e) 
inclusion of any incompetent persons or persons with impaired decision-making capacity:
N/A

 
HIPAA Authorization
12.9 
Section 
For each category below, indicate whether or not this study involves the indicated process:
 HIPAA Authorization
12.9a) Signed
 Yes   
 No
HIPAA/consent waiver or alteration for
 purposes only
12.9b) 
 screening
 Yes   
 No
Full HIPAA 
 or alteration
12.9c) 
waiver
  Yes   
  No
HIPAA 
or waiver is 
 for some or all of the study subjects (e.g. no 
12.9d) 
Authorization 
not required
health data)
  Yes   
  No
 
 HIPAA Waivers and Alterations
12.10
Section 
Describe the purpose/nature of the HIPAA waiver or alteration and 
12.10a) 
list specifically, what 
identifiers and health information are being requested under the waiver/alteration and identify whether 
the waiver is for access, use, and/or collection of this information. 
HIPAA waiver is requested for screening purposes. Veterans with a diagnosis of MCI are sought for this 
study, and the VASDHS Neuropsychological Assessment Unit diagnoses many such Veterans with MCI 
every year. Neuropsychological Assessment Unit records of Veterans diagnosed with MCI will be used to 
identify potential participants. The CPRS records of these potential participants will then be used to 
determine whether they meet the screening criteria for the study. Individuals meeting study criteria will 
be sent a letter inviting them to participate in the study.
The use or disclosure of PHI involves no more than a minimal risk to the privacy of individuals.
12.10b) 
 Agree 
 Disagree
12.10c) The plan to protect the identifiers from improper use and disclosure is adequate.
 Agree 
 Disagree
Describe the plan
The name and last 4 digits of the Social Security Number of each Veteran who meets screening criteria 
and the date of the letter will be kept in a document stored securely on the R drive. These data will be 
stored to ensure that duplicate letters are not sent.
An adequate plan to destroy the identifiers at the earliest opportunity consistent with conduct of 
12.10d) 
the research, unless there is a health or research justification for retaining the identifiers or such 
retention is otherwise required by law (VA Records Control Schedule does not currently permit 
destruction)
 Agree 
 Disagree
Describe the plan
12.10d2) 
Data will only be destroyed according to RCS-10 under Records Control Manager guidance.
By signing this protocol for submission, the PI is providing written assurance that the PHI will 
12.10e) 
not be reused or disclosed to any other person or entity, except as required by law, for authorized 

oversight of the research project, or for other research for which the use or disclosure of protected health 
information would be permitted by the Privacy Rule. 
:  If the waiver of HIPAA 
38 U.S.C. 7332 Information
authorization is for the use of 38 USC 7332 information (applicable to drug abuse, alcohol abuse, HIV 
infection, and sickle cell anemia records), by signing this protocol for submission the PI is providing 
written assurance that the purpose of the data is to conduct scientific research and that no personnel 
involved may identify, directly or indirectly, any individual patient or subject in any report of such 
research or otherwise disclose patient or subject identities in any manner. (Ref:  38 U.S.C. 7332(b)(2)(B))
 Agree 
 Disagree
The research could not practicably be conducted without the waiver or alteration
12.10f) 
 Agree 
 Disagree
Describe how the waiver/alteration enables the research to be conducted
12.10f2) 
We do not have the resources to provide testing to every Veteran with a cognitive complaint, and to do so 
would be replicating clinical services already offered.
The research could not practicably be conducted without access to and use of the PHI
12.10g) 
 Agree 
 Disagree
12.10g2) Describe why it would be impracticable to conduct this research without the PHI described 12.10
a. (v3/8/18)
We will need to ensure that potential participants have a diagnosis of MCI, and we will need their 
addresses to be able to send a letter about the study.
 
 - Alternatives to Participation
Section 13
Describe the alternatives to participation in this research study (see  for guidance)
13) 
?
The alternative to participation is not to participate.
 
 - Potential Risks
Section 14
Describe any potential or known risks or discomforts and assess their likelihood and 
14) 
seriousness.  (see  for guidance)
?
Minimal risk is anticipated with the current investigation. Regarding research risks, participants may 
experience fatigue and/or boredom while completing the interviews, questionnaires, and cognitive tests. 
Some participants may also experience mild anxiety, frustration, and/or stress while reporting on their 
psychiatric symptoms, during assessment procedures if a cognitive test proves difficult for them, and/or 
during the course of group treatment. It is possible that some participants might not experience 
symptomatic relief from the intervention. Participants may experience mild discomfort as a result of being 
audio-recorded during the group sessions. Skin irritation is a possible risk of using the Fitbit.
 
 - Risk Management
Section 15
Describe the procedures for protecting against or minimizing any potential risks/discomforts, and the 
15) 
adequacy of resources for conducting the study and resources participants may need as a consequence of 
the research.  See  for further requirements.
?
If participants experience fatigue, boredom, anxiety, frustration, or stress while completing the 
interviews, questionnaires, and cognitive tests, they will be invited to take a break or return another day 
to complete the assessments.

Study participants will be informed that they may choose to discontinue the study without risk to their 
medical care. 
The Fitbit can be taken off if the participant experiences skin irritation.
COVID Procedures: Participants will be informed that participation in research may increase risk for 
COVID infection and that we will take necessary safety precautions for their safety.
 
 - Privacy and Confidentiality
Section 16
 Provide a brief description of how participant privacy and confidentiality will be protected in this 
16a)
study.
All research records will be labeled with a code number, rather than the name of the participant. A master 
list matching participant names with the code number will be kept in a locked file in the research team’s 
office. Any research records that identify participants will be kept only as paper records in a secure 
VASDHS location, or as files behind the secure VASDHS computer firewall. Any presentations or 
publications from this information will not identify participants by name. Audio recordings of treatment 
sessions will be stored on a VA secure server and will be accessed by Dr. Twamley or her staff for the 
purposes of rating the psychologist’s adherence to the treatment manuals.
See Privacy and Data Security Plan for further details.
16a2) 
 Yes   
 No
 Is SSN used for any purpose other than scanning Consent/HIPAA into the medical record?  (e.g., 
16b)
subject payments, use of clinical record)
 Yes   
 No
If YES, indicate purpose and justification:
16b2) 
SSN is needed for subject payments and last 4 digits are needed to ensure access only to appropriate 
patients in CPRS.
 Section 16.1 Entry of CPRS Notes
Entry of a CPRS 
 is required if any of the following apply:
16.1) 
Research Informed Consent Note
   
The subject is admitted as an inpatient or treated as an outpatient for research
The study involves research medical care or may affect medical care.
The Informed Consent and HIPAA Authorization indicate notes will be entered
    Notes: Scanning the Consent and HIPAA Authorization into CPRS is 
.  Linking the 
no longer required
Consent to the Research Informed Consent Note is permitted (Unless the study has a Certificate of 
        
Confidentiality) and may be especially useful for trials involving the Research Pharmacy.
·
For Non-
Veterans, if Research Informed Consent Notes are entered then the 
 must be 
NOPP Acknowledgement
        
       
scanned in.
·
A 
 should also be entered for each procedure or intervention.
Research Progress Note
·
 
Address the CPRS note requirement:
Is entry of CPRS notes required based on the above criteria?
16.1a) 
 Yes   
 No
Are CPRS notes entered?
16.1b) 
 Yes   
 No
Is a CPRS waiver is requested instead?
16.1c) 

  Yes   
  No
 
 - Potential Benefits
Section 17
Discuss benefits that may be gained by the subject as well as potential benefits to society in 
17) 
general.  (see  for guidance)
?
This research may provide participants with information about their psychological and cognitive 
functioning. Participants may experience a reduction in their complaints regarding cognitive impairment 
and may experience an improvement in their cognitive ability, usage of cognitive strategies, self-efficacy, 
adaptive functioning, and ability to reliably manage personal affairs. They will receive information about 
their activity levels and sleep that they may find helpful. The knowledge gained from this study could lead 
to effective treatments that otherwise might not have been made available. Additionally, study results will 
help expand knowledge of treatments appropriate for Veterans with Mild Cognitive Impairment.
 
 - Risk/Benefit Ratio
Section 18
Discuss why the risks to subjects are reasonable in relation to the anticipated benefits to subjects 
18) 
and in relation to the importance of the knowledge that may reasonably be expected to result.
The risk of increased distress during the assessment, skin irritation due to Fitbit use, or distress 
associated with the treatment components of the study is balanced by the potential benefit of reduced 
distress over time for study participants. The knowledge gained from this study could lead to effective 
treatments that otherwise might not have been made available. Additionally, study results will help 
expand knowledge of treatments appropriate for Veterans with Mild Cognitive Impairment.
 
 - Compensation for Participation
Section 20
Provide all details and justifications of the compensation plan.  See  for detailed requirements.
20) 
?
Participants will be compensated $50 after each of the first three assessments, and $75 after the fourth 
and final follow-up assessment. If participants complete all four assessments, their total compensation will 
be $225. This compensation is provided in consideration of the participants' time and travel. Participants 
who elect to use the Fitbit will be given the device at the end of their study participation.
 
 - Responsibilities and Qualifications
Section 21
Here are the identified study staff members
Elizabeth W. Twamley, PhD
Amy J. Jak, PhD, Amber Victoria Keller, Hannah Lykins, Ingrid Contreras, Paula Michelle Seewald, MA, 
Chantal Muller-Cohn, BA, Chloe T. Green, PhD, Delaney Q. Pickell, Janae Ruth Wyckoff, Jeffrey Hernandez, 
Matthew R. Morgan, Mili Parikh, PhD, Zanjbeel Mahmood, BA, Jacqueline Maye, PhD, Jillian Clark, PhD, 
Ryan Van Patten, Sarah Jurick Lefler, PhD
 Identify here by name those staff working on this protocol, unless they have no contact with subjects 
21)
or identifiable data.  Indicate their role and qualifications.  Also indicate which of the study staff are 
authorized to obtain consent for subjects of VA research.
Dr. Twamley -- PI
Dr. Jak -- Co-Investigator
The above-named study staff are neuropsychologists who will be authorized to obtain consent and deliver 
intervention.
Amber Keller

Chantal Muller-Cohn
Chloe Green
Delaney Pickell
Hannah Lykins
Ingrid Contreras
Jacqueline Maye
Janae Wyckoff
Jillian Clark
Matthew Morgan
Michelle Seewald
Mili Parikh
Ryan Van Patten
Zanjbeel Mahmood
The above-named study staff and trainees will be authorized to obtain consent and to administer 
assessments and deliver intervention. 
Jeffrey Hernandez is a research associate who will manage the eScreening program, but will not have 
contact with participants. Sarah Jurick Lefler may run analyses on coded research databases but will not 
have access to PHI and will not have any contact with participants.
 
 - Bibliography
Section 22
List relevant articles that the IRB can use to provide necessary background for the protocol. Do not 
22) 
include an extensive NIH-grant-style bibliography.  (Up to 5 recommended, but use more if needed to 
support the protocol or citations above.)
Huckans, M., et al., Efficacy of cognitive rehabilitation therapies for mild cognitive impairment (MCI) in 
older adults: working toward a theoretical model and evidence-based interventions. Neuropsychol Rev, 
2013. 23(1): p. 63-80.
Li, H., et al., Cognitive intervention for persons with mild cognitive impairment: A meta-analysis. Ageing 
Res Rev, 2011. 10(2): p. 285-96.
Jak, A.J., The impact of physical and mental activity on cognitive aging. Curr Top Behav Neurosci, 2012. 
10: p. 273-91.
Storzbach, D., Twamley, E.W. (co first authors), et al., Compensatory Cognitive Training for Operation 
Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans with mild traumatic brain 
injury. J Head Trauma Rehabil, in press.
Jak, A.J., et al., Quantification of five neuropsychological approaches to defining mild cognitive 
impairment. American Journal of Geriatric Psychiatry., in press.
 
 - Protocol Attachments
Section 27
If there is any material, such as tables or figures, that are referenced in the protocol text above but not 
pasted into the protocol application these can be attached in the Submission form along with other 
documents such as Consents and HIPAA Authorizations. press Save and Continue
 
Protocol Association to New or Existing Project
Section 28 - 
  
Is this a new R&D Project?.
28) 
 Before you go on to complete the 
 
Initial Review Submission Form
(which is used for attachments), please address the association of this Protocol to an R&D Committee 
Project.  This Protocol may represent a new R&D Project, or it may be an additional Protocol under an 
  
existing R&D Project (such as when a single grant supports multiple Protocols).  Will this Protocol be 
 
submitted to the R&D Committee as a new Project?
  Yes   
  No

 
Existing Project Association
Section 29 - 
  
The associated R&D Project should already exist in the database.
29) 
 Identify the R&D Project(s) that 
 
correspond to this protocol.
Project Status
Proposal Number
Project Title
Principal 
Investigator
Approved
1195749
1195749
Elizabeth W. 
Twamley, 
PhD
Cognitive Rehabilitation for Older Veterans with 
Mild Cognitive Impairment
 The Protocol Application is now complete for a Protocol attached to an 
existing Project.
 
Next you will go on to the Initial Review Submission Form.  This form is used 
to collect the Application and any other needed attachments for submission to 
the IRB for review.
Press Save and Continue

Department of  Veterans Affairs 
RESEARCH INFORMED CONSENT   Page 1 of 4 
                                         IRB Protocol #: H170016
Title of Study: 
Cognitive Rehabilitation for Older Veterans with Mild Cognitive Impairment
Principal Investigator:
Elizabeth W. Twamley, PhD
VAMC:
VA San Diego Healthcare System
10-1086 VASDHS 20150220 
This document must be stamped 
by the IRB with approval dates
   
1 hk
             
1) Purpose of this research study
Elizabeth W. Twamley, PhD is conducting a research study to find out more about treatments 
for Mild Cognitive Impairment. You have been asked to participate because you have been 
diagnosed with Mild Cognitive Impairment. There will be approximately 108 participants at this 
VA site and 108 participants at the Portland VA site. There will be a total of 216 participants at 
both sites.
2) How long the study will take
Your participation will take approximately 1-3 hours each time you come to the VA hospital, and 
you will be expected to come to the hospital 12 times over a 6-month period (4 times for 
assessments and 8 times for treatment groups). The entire study will take about 5 years.
3) What will happen to you in this study 
If you agree to be in the study, the following will happen to you:
A. At your first visit you will receive information regarding this study and have an opportunity 
to ask questions regarding study participation. If you agree to participate in the study, you 
will sign this informed consent document. You will then take part in an assessment of 
your cognition, symptoms, and functioning, which will take approximately 3 hours.
B. You will be randomly assigned (like the flip of a coin) to receive Goal-Focused Treatment 
or Compensatory Cognitive Training. Both treatments will involve weekly groups with a 
psychologist for approximately 2 hours per week for 8 weeks. Goal-Focused Treatment 
includes setting and achieving short-term and long-term goals for improving cognition and 
functioning. Compensatory Cognitive Training includes training in strategies to improve 
cognition, stress management, and improving nutrition and exercise. Treatment sessions 
will be audiotaped to ensure that the psychologist is following the treatment manual.
C. You will also complete repeat assessments of your cognition, symptoms, and functioning 
at 4 weeks, 8 weeks, and 21 weeks after you begin treatment. The 4-week assessment 
session will take about 1 hour and the 8-week and 21-week assessment sessions will 
take about 3 hours each.
COVID-19 Safety Procedures: All assessment and intervention procedures will be completed 
using social distancing whenever possible. All group members and facilitators will be required to 
wear a medical grade procedure mask for the entire duration of the intervention sessions.
4) Which procedure(s) or treatment(s) are done for research only
All assessments are done for research only. The treatments provided in this study include 
approaches to address cognitive and functioning problems. Neither treatment is part of standard 
care; both treatments are experimental. In this study, we will be comparing the two treatments to 
see which works best. 
Subject Name:
Date:
VA San Diego Healthcare System
IRB NUMBER: H170016
IRB APPROVAL DATE: 04/13/2021

Department of  Veterans Affairs 
RESEARCH INFORMED CONSENT   Page 2 of 4 
                                         IRB Protocol #: H170016
Title of Study: 
Cognitive Rehabilitation for Older Veterans with Mild Cognitive Impairment
Principal Investigator:
Elizabeth W. Twamley, PhD
VAMC:
VA San Diego Healthcare System
10-1086 VASDHS 20150220 
This document must be stamped 
by the IRB with approval dates
   
1 hk
5) RISKS reasonably to be expected
Participation in this study may involve some added discomforts. The procedures used may 
cause: 
A. Fatigue, boredom, or stress while completing the assessments.
B. Discomfort as a result of the audiotaping of treatment groups.
C. As with any research study, the possibility of breach of confidentiality exists.
D. Participation in research may increase your risk for COVID infection.
Unforeseeable RISKS 
Because this is an investigational study there may be some unknown risks that are currently 
unforeseeable.  You will be informed if the researchers learn of any change in the amount of risk 
to you.
6) BENEFITS reasonably to be expected.
There may or may not be a direct benefit to you from these procedures. The investigator, 
however, may learn more about treatments for Mild Cognitive Impairment.
7) Voluntary nature of participation and right to withdraw without penalty.
Participation in research is entirely voluntary. You may refuse to participate or withdraw at any 
time without jeopardy to the medical care you will receive at this institution or loss of benefits to 
which you are entitled.  
8) Alternatives to the research procedure or treatment 
The alternative to participation is not to participate.
9) Procedure for the orderly termination of a volunteer’s participation
If you decide that you no longer wish to participate in this study please call Dr. Twamley at 858-
642-3848. Your participation in this study may be stopped if the investigator decides that 
stopping is in your best interest or if you do not participate in assessments or treatment.
10) Information learned from the study will be shared with you
While you are a participant in this study you will be told if any important new information is found 
that may affect your wanting to continue. If the results of this research might influence your 
medical care after you have completed your participation, the investigators will contact you to let 
you know these results.
11) Care provided if you are injured as a result of this study
The VA will provide necessary medical treatment should you be injured as a result of 
participating in this study and following study procedures.  You will be treated for the injury by 
the VA at no cost to you or your insurance but no additional compensation is available. 
12) Privacy and confidentiality
VA San Diego Healthcare System
IRB NUMBER: H170016
IRB APPROVAL DATE: 04/13/2021

Department of  Veterans Affairs 
RESEARCH INFORMED CONSENT   Page 3 of 4 
                                         IRB Protocol #: H170016
Title of Study: 
Cognitive Rehabilitation for Older Veterans with Mild Cognitive Impairment
Principal Investigator:
Elizabeth W. Twamley, PhD
VAMC:
VA San Diego Healthcare System
10-1086 VASDHS 20150220 
This document must be stamped 
by the IRB with approval dates
   
1 hk
Participation in this study may involve a loss of privacy, but information about you will be 
handled as confidentially as possible. Your participation in study assessments and any study-
related treatment will be documented in your electronic medical record. 
Your research records will be labeled with a code number. The list that matches your name with 
the code number will be kept in a locked file in the research team’s office. Any research records 
that identify you will be kept only as paper records in a secure VASDHS location, or as files 
behind the secure VASDHS computer firewall. Any presentations or publications from this 
information will not identify you. Audio recordings of treatment sessions will be stored on a VA 
secure server and will be accessed by Dr. Twamley or her staff for the purposes of rating the 
psychologist’s adherence to the treatment manuals.
This study includes collection of your social security number for the purpose of providing you 
compensation. 
We will keep confidential all research and medical records that identify you to the extent allowed 
by law.  However, you should know that there are some circumstances in which we may have to 
show your information to other people.  For example, the Federal Office of Human Research 
Protections, the General Accounting Office, the VASDHS R&D Committee, the VASDHS 
Institutional Review Board, VA Clinical Science Research and Development, and federal 
compliance officers may look at or copy portions of records that identify you. 
13) Payment
Costs to you or your insurance 
There will be no costs to you or your insurance for any procedures or testing done only as part 
of this research study.  If you receive a bill for services that you think could be related to your 
participation in this study, you should contact Dr. Twamley.
Medical care and services provided by the VA that are not part of this study (e.g., normal 
hospital and prescription expenses which are not part of the research study) may require co-
payments if your VA-eligibility category requires co-payment for VA services.  
Payment for participating
In consideration of your time, you will receive a payment of $50 for each of the first three 
assessments you complete in this study, and $75 after the fourth and final follow-up 
assessment. The maximum compensation for participating in the study is $225. Payments will 
be made directly to your bank account using electronic funds transfer. If you currently have a 
debt to the Federal Government, your debt may be subtracted from your funds transfer payment 
for study participation.
14) Additional Information
The VA San Diego Healthcare System provides oversight and resources for this study.  
Financial support for this study is provided by VA Clinical Science Research and Development.
VA San Diego Healthcare System
IRB NUMBER: H170016
IRB APPROVAL DATE: 04/13/2021

Department of  Veterans Affairs 
RESEARCH INFORMED CONSENT   Page 4 of 4 
                                         IRB Protocol #: H170016
Title of Study: 
Cognitive Rehabilitation for Older Veterans with Mild Cognitive Impairment
Principal Investigator:
Elizabeth W. Twamley, PhD
VAMC:
VA San Diego Healthcare System
10-1086 VASDHS 20150220 
This document must be stamped 
by the IRB with approval dates
   
1 hk
A description of this clinical trial will be available on http:\\www.ClinicalTrials.gov, as required by 
US law. This website will not include information that can identify you. At most, the website will 
include a summary of the results. You can search this website at any time.
Re-contact. 
 (initial here) I consent to being contacted by phone for possible participation in future 
studies.
Disclosure of Results. During your final study visit, Dr. Twamley and/or the study coordinator 
will provide verbal feedback and/or answer questions you may have about the results obtained 
in the course of your study participation.
15) RESEARCH SUBJECTS' RIGHTS: You have read or have had read to you all of the above. 
You have been informed that you do not have to take part in this study, and your refusal 
to participate will involve no penalty or loss of rights to which you are entitled. You may 
withdraw from this study at any time without penalty or loss of VA or other benefits to 
which you are entitled.
In the event of illness or injury that you believe to be related to the study, or have questions 
about this research, you can call Dr. Twamley at 858-642-3848. If you have any questions or 
concerns about your rights as a research subject, the validity of a research study, or research 
personnel you can contact the Research Compliance Officer at 858-642-3817, VA Research 
Service at 858-642-3657, VA Regional Counsel at 858-642-1540, or the VASDHS Human 
Research Protection Program at 858-642-6320.
__________________ has explained the study to you and answered all of your questions. You 
have been told of the risks or discomforts and possible benefits of the study.  You have been 
told of other choices of treatment available to you.  You will receive a copy of this consent form 
and a copy of the Health Insurance Portability and Accountability Act (HIPAA) Authorization that 
you signed.  You will also receive a copy of the California Experimental Subject's Bill of Rights. 
By signing this form you indicate that you have been informed of your rights as a research 
subject, and that you voluntarily consent to participate in this study.  You have been informed 
what the study is about and how and why it is being done.
Subject's Signature
Date
               
            
                   
     
Signature of Researcher obtaining consent 
           Name (print)         
        Date
VA San Diego Healthcare System
IRB NUMBER: H170016
IRB APPROVAL DATE: 04/13/2021