The MObile AssessMENT of Behavioral and Psychological Symptoms of Dementia in Amnestic Mild Cognitive Impairment and Alzheimer's Disease (MOMENT) Study: A Randomized Controlled Trial
Phase: NA
Conditions: Alzheimer Disease, Mild Memory Disturbance, Mild Cognitive Impairment
Sponsor: Indiana University

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The MObile AssessMENT of Behavioral and 
Psychological Symptoms of Dementia in Amnestic 
Mild Cognitive Impairment and Alzheimer’s Disease 
(MOMENT) Study: A Randomized Controlled Trial 
 
 
 
Principal Investigator: 
Daniel R. Bateman MD, Assistant Professor 
Department of Psychiatry, Indiana University School of Medicine 
Indiana University Center for Aging Research, Regenstrief Institute, Inc. 
1101 West 10th Street 
Indianapolis, IN 46202 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Support Provided by: 
National Institute on Aging (NIA) 
1K23AG059914-01A1 
 
 
 
 
 

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Table of Contents: 
 
Study Schema 
1.0 
Background & Rationale 
2.0 
Objective(s) 
2.1 
Primary Objective 
2.2 
Secondary Objective 
2.3 
Tertiary/Exploratory/Correlative Objectives 
3.0 
Outcome Measures 
3.1 
Primary Outcome Measures 
3.2 
Secondary Outcome Measures 
3.3 
Tertiary/ Exploratory/ Correlative Outcome Measures 
4.0 
Eligibility Criteria 
4.1 
Inclusion Criteria 
4.2 
Exclusion Criteria 
5.0 
Study Design 
6.0 
Enrollment/Randomization 
7.0 
Study Procedures 
8.0 
Study Calendar 
9.0 
Reportable Events 
10.0 Data Safety Monitoring 
11.0 Study Withdrawal/Discontinuation 
12.0 Statistical Considerations 
13.0 Data Management 
14.0 Privacy/Confidentiality Issues 
15.0 Follow-up and Record Retention 
16.0 References 
 

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Abbreviations 
 
AD 
Alzheimer’s Disease 
AE 
Adverse Event 
aMCI 
Amnestic Mild Cognitive Impairment 
BCN 
Brain CareNotes mobile application 
BPSD 
Behavioral and Psychological Symptoms of Dementia 
COC 
Certificate of Confidentiality 
DOB 
Date of Birth 
DSMP 
Data Safety Monitoring Plan 
DRE 
Disease-Related Event 
EC 
Enhanced Care 
eCRF 
Electronic Case Report Forms 
EMA 
Ecological Momentary Assessment 
EMR 
Electronic Medical Record 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HABC 
Healthy Aging Brain Center 
HIPAA 
Health Insurance Portability and Accountability Act  
IDE 
Investigational Device Exemption 
IRB 
Institutional Review Board 
LAR 
Legally Authorized Representative 
MCI 
Mild Cognitive Impairment 
MMSE 
Mini Mental Status Exam 
MRN 
Medical Record Number 
NCT 
National Clinical Trial 
NIA 
National Institute on Aging 
NIH  
National Institutes of Health 
NPI-Q 
Neuropsychiatric Inventory Questionnaire 
NPS 
Neuropsychiatric Symptoms 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
PSS-14 
Perceived Stress Scale-14 
QA 
Quality Assurance 
QC 
Quality Control 
RA 
Research Assistant 
SAE 
Serious Adverse Event 
SECBCI Sandra Eskenazi Center for Brain Care Innovation 
SILS 
Single Item Literacy Screener 
SO 
Safety Officer 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
SUS 
System Usability Scale 
UP 
Unanticipated Problem 
ZBI 
Zarit Burden Interview 

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1.0 
Background & Rationale 
 
The National Plan to Address Alzheimer’s disease (AD) and the National Institute on 
Aging (NIA) emphasize the importance of research exploring the use of technology to 
assess and improve health. Researchers at the NIA 2015 AD Research Summit 
recommended research on “in-place monitoring” of persons living with dementia to 
better understand disease progression and investing “in research to develop new 
technologies that enhance the delivery of clinical care, caregiver support and in-home 
monitoring11.” The purpose of the proposed research is to improve the day-to-day 
management of behavioral and psychological symptoms of dementia (BPSD) among 
persons living with dementia. By international consensus, behavioral and psychological 
symptoms of dementia (BPSD) consist of disturbed perception, thought content, mood 
and behavior12. Prevalence of BPSD range from 80% to 98%13–17. BPSD negatively 
impact a patient’s quality of life18, predict functional decline19, and lead to greater 
financial costs20. Early onset of BPSD also strongly predicts caregiver burden26–32.  
 
Currently, most clinicians and investigators assess BPSD in the Alzheimer’s disease 
(AD) population using standardized paper and pencil scales in the office setting. The 
problem is that BPSD surveillance as it stands in clinical practice today is typically 
episodic, cross-sectional and completed at the time of routine office visits, if it is 
completed at all. Recall bias and environmental setting of symptom measurement (clinic 
vs. home) can lead to differences in symptom reporting7,8, as can a caregiver’s 
emotional state and severity of caregiver burden5,6. Clinic-based episodic measurement 
may not effectively capture, nor allow timely treatment of, emerging or changing BPSD. 
Indeed, patients and caregivers may go months without addressing BPSD until they 
reach a state of crisis leading to emergency department visits, overuse of high-risk 
psychotropic medications, or caregiver exhaustion. Many questions remain surrounding 
the topic of how often care teams should monitor BPSD and whether increased 
surveillance in the home would provide actionable data that would improve patient and 
caregiver outcomes. 
 
Mobile Ecological Momentary Assessment (EMA) represents a cutting edge, 
technological approach to capturing symptoms in the moment that addresses a costly, 
national challenge of caring for persons with BPSD. Early studies examining the use of 
mobile EMA in caregivers with dementia suggest proof of concept and demonstrate 
differences in the clinic-based vs. mobile EMA symptom assessment. Technology can 
provide timelier, and more frequent measurements of patient symptoms than ever 
before. While monitoring BPSD every 6 months is likely not enough, based on end-user 
feedback in our pilot studies, daily symptom assessment may be too frequent.  
 
The long-term goal of the proposed work is to improve the care of individuals with AD in 
the mild cognitive impairment (MCI) stage and in the dementia stage of the illness. This 
will be done via creation of a more effective clinical approach to the measurement of 
BPSD and caregiver distress that will allow for more timely and effective care. 
 

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Our proposal objectives are to determine the feasibility and the optimal frequency of 
mobile surveillance of BPSD among aMCI and AD patients and their family caregivers 
through the employment of ecological momentary assessment (EMA), a repeated 
sampling method of symptoms that utilizes near real-time and natural environment data 
collection. The central premise is that increased frequency of measurement of BPSD 
and caregiver distress will lead to timelier, actionable data which will lead to timely care 
and improved outcomes for persons living with dementia and their caregivers. 
 
The study design randomizes assignment of 154 patient-caregiver dyads (n=308 human 
subjects) to an active or control group; and, a 2 x 6 cross over design within the active 
group, wherein patient-caregiver dyads who are assigned to the active group are further 
randomly assigned to start with either weekly or monthly surveillance frequencies. They 
then cross-over every month to the other frequency condition, over a 6-month time 
horizon wherein each dyad will act as their own control. Subjects will be recruited from 
the Eskenazi Health, Sandra Eskenazi Center for Brain Care Innovation (SECBCI). The 
surveillance will be paired with standard SECBCI clinic BPSD treatment protocols in 
order to:  
 
AIM 1: Quantitatively and qualitatively, determine the feasibility of collecting responses 
on an ecological momentary assessment (EMA) version of the Neuropsychiatric 
Inventory Questionnaire (NPI-Q), via the Brain CareNotes Mobile Application (BCN), 
from caregivers randomly assigned to using smartphone technology at differing 
frequency intervals, compared with a control group with data collected without the 
mobile health version and only at baseline and 6 months). H1: Caregivers in the 
intervention groups will complete the assessments via smartphone and report an 
acceptable response burden.  
 
AIM 2: Determine whether more frequent surveillance of BPSD yields more actionable 
data. H2: We expect there to be more occurrences of “actionable data” in the groups 
(i.e., intervention vs control) or conditions within a group (i.e., weekly vs monthly 
condition within the intervention group) that have more frequent monitoring. We define 
actionable data as data that could lead to a change in care plan. This was 
operationalized by setting “clinically significant” thresholds for NPI-Q symptoms 
 
AIM 3: Explore whether different surveillance intervals are associated with greater 
improvement in BPSD and caregiver distress. H3: Groups or conditions within a group 
that receive more frequent surveillance paired with response to “clinically significant” 
symptoms will have greater improvement in BPSD and in caregiver distress. 
 
The expected outcomes are data that support an optimal measurement frequency of 
BPSD, demonstration of the feasibility of collecting these data in-home using widely 
available mobile technology, and early evidence that these assessments provide 
opportunities to improve BPSD. We expect these data will also be used to assess for 
associations between BPSD surveillance intervals (weekly or monthly), actionable data 
and characteristics. Data pertaining to feasibility and usability and to the impact of the 
intervention on BPSD and caregiver distress we expect will support an R01 application 

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to trial monitoring and just-in-time interventions in a fully powered RCT where the 
primary outcomes will be emergency room, hospital and psychotropic medication 
utilization. 
 
 
Significance: The National Institute on Aging (NIA), the National Plan to Address 
Alzheimer’s disease (AD), and the NIH all emphasized the value and prioritization of 
using technology to assess and improve health. Researchers at the NIA 2015 AD 
Research Summit formulated many recommendations on AD and technology. They 
included (1) supporting the development and use of in-place monitoring of patients to 
better understand disease progression, (2) integrating pervasive computing approaches 
into AD clinical trials to allow for continuous data capture of everyday symptoms and 
activities, (3) integrating mobile health (mHealth) technologies for assessment and 
disease monitoring into the healthcare system and (4) investing “in research to develop 
new technologies that enhance the delivery of clinical care, caregiver support and in-
home monitoring11.” The 2015 update to the National Plan to Address AD stressed the 
use of health information technology to support the needs of individuals with AD and 
related dementias. The NIA and National Plan to Address AD are not alone, the NIH 
listed the application of mHealth technologies to enhance health promotion and disease 
prevention as a priority in their NIH-Wide Strategic Plan for Fiscal years 2016-202033. 
 
Studies estimate that over 5.5 million people in the U.S. suffer from ADRD34. By 2025 
the number of adults age ≥65 with AD will increase to 7.1 million, a 35% increase over 
2017 estimates34,35. Experiencing at least one BPSD in the course of dementia is almost 
universal, with BPSD prevalence ranging from 80% to 98%13–17, meaning that 
somewhere between 4.4 and 5.4 million people with ADRD will suffer from BPSD.  
Persons with BPSD experience a more rapid disease progression, greater mortality21–23 
and earlier nursing home placement23–25. One study estimates that BPSD accounts for 
30% of annual expenditures on ADRD care36. Morris et al identified the cost associated 
with agitation, one of the most distressing and potentially dangerous types of BPSD, to 
have a mean excess cost of $5539 per person with ADRD annually37,38.  
 
Not only does BPSD carry a financial cost, there is a significant psychological and 
physical cost to caregivers. Caregivers of persons with dementia report higher rates of 
depression, lower subjective wellness and worse physical health as compared to non-
caregivers39. A meta-analysis estimated caregiver prevalence rates of depressive and 
anxiety symptoms to be 34 and 44%40. Multiple longitudinal studies show that onset of 
BPSD early in the disease course increases in BPSD strongly predict caregiver 
burden26–32. A meta-analysis of 228 studies calculated the BPSD correlational co-
efficient for caregiver burden and depression to be 0.37 and 0.27 respectively30,41. For 
perspective, the cognitive impairment correlational co-efficient for the same meta-
analysis were lower at 0.18 and 0.1630,41. BPSD is a much greater contributor to 
caregiver burden and depression than cognitive impairment. 
 
Only in the past 20 years have clinicians, investigators and nursing home administrators 
come to recognize the importance of assessment and treatment of BPSD. Previously, 

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cognitive symptoms and functional impairment were the focus of ADRD research. In 
1996, a consensus conference of dementia specialists developed a consensus 
statement on BPSD current knowledge and implications for research and treatment12. 
They defined BPSD as an integral element of the dementia disease process, consisting 
of signs and symptoms of disturbed perception, thought content, mood and behavior12. 
The consensus concluded that BPSD symptoms present significant problems to all 
those who interact with persons with dementia, for society and health systems. 
Observational studies support this claim.  
 
Until curative treatment of ADRD is available, non-pharmacologic and pharmacologic 
interventions are the only options for symptom management of BPSD. Only after 
clinicians are able to accurately assess BPSD, can they effectively apply interventions 
to help improve outcomes for ADRD patients.   
 
 
Innovation: The integration of health technology with ADRD assessment and treatment 
interventions is a national priority. Currently, most clinicians and investigators assess 
BPSD via interview and standardized scales in the office setting. Using mobile EMA to 
measure BPSD in real-time and real-place (natural environment) provides an 
opportunity for clinicians to understand BPSD symptomatology through a richer and 
potentially more accurate source of data. Repeated sampling has the advantage of 
decreased measurement error. These data can provide more meaningful opportunities 
to treat BPSD and to measure treatment response.  
 
A mobile surveillance approach also leverages the science of behavioral economics, a 
field that merges the schools of psychology and economics to better understand human 
behavior and decision making. Psychologists Barbara Fredrickson and Daniel 
Kahneman, demonstrated that 94% of the variance in subjects’ global evaluations of 
recalling past experiences of discomfort was attributable to the combination of peak 
discomfort and discomfort at the time of last measurement1. They described this as the 
Peak-End Rule. This was seen in a study of patients receiving colonoscopies (n=682) 
randomized to a modified procedure that reduced pain at the end of the procedure. 
Those with reduced pain at the end of the procedure rated their whole experience as 
less painful2. In another experiment, subjects were exposed to the aversive event of 
placing their hand in cold water. Subjects expressed a preference for a longer exposure 
to cold water (longer duration of pain) over a shorter exposure to colder water (shorter 
duration with more intense pain)3. We often assume that patients or caregivers fill out 
scales using a weighted average during the past time interval, yet the Peak-End Rule, 
argues against this assumption and provides the underlying logic for using more 
frequent measurement to assess experiences closer to real-time.  
 
Mobile surveillance represents a cutting edge, technological approach, to addressing a 
costly, national problem of BPSD. The studies examining the use of mobile surveillance 
in caregivers with dementia and older adults are small in number and more work needs 
to be done in this area.  
 

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2.0 
Objective(s) 
 
AIM 1: Quantitatively and qualitatively, determine the feasibility of collecting responses 
on an ecological momentary assessment (EMA) version of the Neuropsychiatric 
Inventory Questionnaire (NPI-Q), via the Brain CareNotes Mobile Application (BCN), 
from caregivers randomly assigned to using smartphone technology at differing 
frequency intervals, compared with a control group with data collected without the 
mobile health version and only at baseline and 6 months). H1: Caregivers in the 
intervention groups will complete the assessments via smartphone and report an 
acceptable response burden. 
 
AIM 2: Determine whether more frequent surveillance of BPSD yields more actionable 
data. H2: We expect there to be more occurrences of “actionable data” in the groups 
(i.e., intervention vs control) or conditions within a group (i.e., weekly vs monthly 
condition within the intervention group) that have more frequent monitoring. We define 
actionable data as data that could lead to a change in care plan. This was 
operationalized by setting “clinically significant” thresholds for NPI-Q symptoms 
 
AIM 3: Explore whether different surveillance intervals are associated with greater 
improvement in BPSD and CG distress. H3: Groups or conditions within a group that 
receive more frequent surveillance paired with response to “clinically significant” 
symptoms will have greater improvement in BPSD and in caregiver distress. 
 
 
3.0  
Outcome measures and mobile application 
3.1 
Primary outcome measures 
 
3.1.1  The Neuropsychiatric Inventory Questionnaire – (NPI-Q): was developed as 
a more clinically relevant version of the original neuropsychiatric inventory. It is a self-
administered questionnaire completed by a person who cares for a patient with AD or 
dementia. There are 12 domains in the NPI-Q each focused on a different and specific 
BPSD. The domains are as follows: delusions, hallucinations, agitation/aggression, 
depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, 
irritability/lability, motor disturbance, nighttime behaviors and appetite/eating. Each is 
noted as present “yes” or absent “no”. If the informant answers “yes” to a symptom 
question they then are asked follow up questions on the symptom severity (mild, 
moderate, severe) and the amount of distress the symptoms causes them (the 
caregiver) on a 5-point scale19. On average the NPI-Q takes 5 minutes to complete.  
 
3.1.2 The Brain CareNotes mobile application (BCN) was developed by Regenstrief 
Institute investigators Drs. Bateman, Holden and Boustani, and Cathy Alder. BCN takes 
all of the questions of the NPI-Q and delivers the questions from the scale to the 
caregiver through a smartphone mobile app that pings the caregiver on their phone at a 
set frequency, prompting the caregiver to complete the questionnaire. The app is 
designed for ecological momentary assessment (EMA) and is HIPPA compliant with 
secure transfer of data from the app to a secure cloud-based database. Ecological 

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momentary assessment is the approach to gathering survey data from individuals in real 
time in the individuals’ real environment. Our study will be surveying individuals at 
different intervals, making it similar to an EMA approach.  
 
BCN is not intended to function as a medical device. BCN does not meet the software 
definition of a medical device as clarified in the updated 2019 FDA Policy for Device 
Software Functions and Mobile Medical Applications Guidance for Industry and Food 
and Drug Administration Staff. Section 201 (h) of the FD&C ACT defines a medical 
device as “…an instrument, apparatus, implement, machine, contrivance, implant, in 
vitro reagent, or other similar or related article, including any component, part, or 
accessory”, that is “… intended for use in the diagnosis of disease or other conditions, 
or in the cure, mitigation, treatment, or prevention of disease, in man …” or “… intended 
to affect the structure or any function of the body of man or other animals…” and “does 
not include software functions excluded pursuant to section 520(o) of the FD&C Act.” 
(https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-
device-software-functions-and-mobile-medical-applications).  
 
BCN is intended to be used as a mobile application that helps facilitate communication 
between caregivers and members of a patient’s treatment team. It is not a treatment 
onto itself.  
 
3.1.3  Feasibility will be measured 5 different ways: 
1) Completion rate of the NPI-Q through the BCN app by the aMCI or AD caregiver 
over the 6-month intervention period.  
2) Quantitative answers to the burden of scale completion question will be asked every 
time the NPI-Q is completed. “How burdensome was completion of the prior scale 
(Answer options: not at all burdensome, mildly burdensome, moderately 
burdensome, or extremely burdensome)”. 
3) Completion rate of the semi-structured BPSD phone questionnaires triggered by 
“clinically significant” symptoms entered by the caregiver into the BCN application. 
4) aMCI and AD Caregiver Feasibility and Usability Survey (3mo, 6mo, quantitative). 
5) aMCI and AD Caregiver Feasibility and Usability Semi-Structured Interview (3mo, 
6mo, qualitative). 
 
3.1.4  Usability will be measured 3 different ways:  
1) System Usability Scale  
2) aMCI and AD Caregiver Feasibility and Usability Survey (3mo, 6mo, quantitative) 
3) aMCI and AD Caregiver Feasibility and Usability Semi-Structured Interview (3mo, 
6mo, qualitative) 
 
3.1.5  Other relevant outcome measures 
1) Caregiver and Patient Demographics 
2) Zarit Burden Interview (baseline, 3mo, 6mo) – Validated measure of caregiver 
burden 
3) Perceived Stress Scale 14 (PSS-14, baseline, 3mo, 6mo) – Validated measure of 
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4) Healthy Aging Brain Center Caregiver Version (HABC-CG) – Validated measure of 
BPSD developed by faculty at the Sandra Eskenazi Center for Brain Care Innovation 
(SECBCI), and used routinely in their memory subspecialty clinic. 
 
3.2.0  Secondary outcome measures 
3.2.1  Actionable data - we define actionable data as data that could lead to a change 
in care plan (e.g. diagnostics, medication change, etc.). This was operationalized by 
setting “clinically significant” thresholds for NPI-Q symptoms and caregiver distress (see 
research design and methodology overview) that when reached leads to contact and 
interval assessment of the caregiver by the research team. Clinical teams are then 
notified by research team about findings. We will compare groups and conditions on the 
percentage of participants in each group or each condition that met at least one 
“clinically significant” threshold per month. 
 
3.3.0  Exploratory outcome measures 
3.3.1  Change in rating of BPSD - calculated by the difference in NPI-Q total scores 
(baseline, 3-mo, 6-mo). The intervention group will be compared to the control group for 
the same time intervals.  
 
3.3.2  Change in caregiver distress - calculated by the difference in NPI-Q caregiver 
distress total scores (baseline, 3-mo, 6-mo). The intervention group will be compared to 
the control group during the same time intervals. 
 
4.0   Eligibility criteria   
4.1.1   Inclusion criteria 
To be eligible for participation in this study, a patient caregiver dyad must meet the 
following inclusion criteria: 
 
1. The patient has received a diagnosis of Amnestic Mild Cognitive Impairment 
(aMCI) or probable or possible Alzheimer’s disease (AD) and receives his or her 
care at the Eskenazi Health, Sandra Eskenazi Center for Brain Care Innovation. 
2. The patient has a caregiver who is willing to participate in the study. 
3. The caregiver is at least 18 years of age and does not have visual impairment 
significant enough to interfere with the use of a smartphone.  
4. Both the patient and caregiver live in the community setting in Indiana. 
5. The patient is also eligible if they live in an independent or assisted living facility. 
6. In cases where the patient with AD lacks capacity to consent to research, he or 
she must have a legally authorized representative (LAR) to consent on his or her 
behalf.  
7. In cases where the patient lacks capacity to consent to research, he or she will 
be given an opportunity to provide assent. If the patient is unable to provide 
assent, an observable dissent will be honored. 
8. The caregiver reports having contact with the patient with aMCI or AD at least 
weekly on average. The reported contact can be in person, over the telephone, 
or via a video call, like Zoom or FaceTime.   
 

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4.2.1 Exclusion Criteria 
1. The patient and/or caregiver have a history of serious mental illness 
(schizoaffective disorder, schizophrenia, bipolar disorder) 
2. The participant is participating in another caregiver intervention research study 
3. The participant lacks both the capacity to consent and a legally authorized 
representative (LAR) 
4. The potential participant with a diagnosis of either aMCI or AD communicates 
observable dissent. 
5. If the patient lives in a long-term care facility. 
 
 
5.0   
Study Design 
The purpose of the following randomized control trial is to determine: 1) the feasibility 
and usability of the Brain CareNotes mobile application (BCN) intervention to deliver 
ecological momentary assessment (EMA) surveillance of Behavioral and Psychological 
Symptoms of Dementia (BPSD) and caregiver distress in amnestic mild cognitive 
impairment (aMCI) or Alzheimer’s Disease (AD) caregivers, 2) the optimal surveillance 
frequency and 3) whether improved BPSD surveillance can improve opportunities to 
intervene.  
 
The BCN intervention delivers the Neuropsychiatric Inventory Questionnaire (NPI-Q) to 
caregivers of patients with either aMCI or AD to monitor BPSD and caregiver distress.  
During the study caregivers in the intervention group will be asked to answer an EMA 
version of the NPI-Q on the BCN intervention at differing intervals (weekly or monthly).  
 
We propose to enroll 154 aMCI and AD patient-caregiver dyads from our memory care 
practice at Eskenazi Health, Sandra Eskenazi Center for Brain Care Innovation 
(SECBCI), an urban safety net hospital in Indianapolis in a 6-month randomized 
controlled trial of EMA assessment to monitor BPSD compared to enhanced care. 
Subject dyads will be randomized to either the intervention or control group in a 1:1 ratio 
(77 per group). The control group will not receive the BCN intervention. However, the 
caregivers in the control group will be administered most of the same assessments at 
the baseline, 3-month and final (6-month) visit as the caregivers in the intervention 
group, except for the two assessments that ask questions related to the mobile 
application. Caregivers will also participate in semi-structured interview at the baseline 
visit, final visit and when triggered by “clinically significant” BPSD. 
 
The study design includes six 1-month periods. Those in the intervention group will be 
nested in a 2 x 6 cross-over design in which they will be randomly assigned to start with 
1 of 2 schedules of EMA surveillance frequency (1) weekly or (2) monthly. The 
intervention participants will then cross-over at the end of each and every month to the 
other surveillance frequency condition, over a 6-month time horizon. The crossover 
design allows efficient sample size reduction for the comparison between two higher 
frequency arms by allowing persons to serve as their own controls for a within person 
intervention effect. According to standard analysis of cross-over trials, the comparison 

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of the two EMA surveillance frequency conditions within the intervention group will be 
tested with a within-subjects test. Co-variates and biological variation including sex will 
be incorporated into the analysis. 
 
Table 1. Study Characteristics 
Stage of Behavioral Intervention Development: 
Stage II 
NIH Phase III Clinical Trial?   
No 
Multiple Site Trial?    
 
No 
Brief Description of Study Design 
Study participants, 154 caregiver-patient dyads with amnestic mild cognitive 
impairment (aMCI) or Alzheimer’s Disease (AD) Dementia (308 human subjects) will 
be randomly assigned to Enhanced Care (EC, 77 dyads) or the BCN Intervention + 
EC (77 dyads). 
 
Enhanced Care 
(EC) x (6-mo) 
 Dementia collaborative care provided through the 
Sandra Eskenazi Center for Brain Care Innovation 
(SECBCI).  
 
 Services include care coordination, and evidenced based 
assessment and treat protocols for behavioral and 
psychological symptoms of dementia (BPSD). 
 
Brain CareNotes 
(BCN) App + EC x 
(6-mo) 
 
 
 
 
 
 The Brain CareNotes (BCN) app was developed with a 
user centered design for patients with MCI and AD, 
caregivers and healthcare team members.  
 
 The BCN app will deliver the Neuropsychiatric Inventory 
Questionnaire (NPI-Q) to the caregiver to report on the 
patient’s BPSD severity and associated caregiver 
distress severity.  
 
 The NPI-Q delivery frequency will alternate every 30 
days between conditions of weekly or monthly delivery. 
These set frequencies of weekly and monthly, will be re-
evaluated and possibly modified based on feedback from 
the first 10 participants in the intervention arm. 
 
 If BPSD as measured by the NPI-Q rises to a set 
severity threshold then this data will be shared with the 
patient’s treatment team who will contact the caregiver 
for further evaluation.  
 
 
 
 

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Table 2. Defining Clinically Significant BPSD and Responses to BPSD 
Clinically 
Significant BPSD 
Severity Threshold 
 
 Clinically Significant BPSD will be defined as when any 
NPI-Q severity domain = 3 regardless of caregiver 
distress, or whenever NPI-Q caregiver distress is marked 
as “moderate”  “severe” or “very severe”. 
Response to 
Clinically 
Significant BPSD 
 
1. Automatic free response follow up questions (via BCN). 
 
2. Automatic notification of research team. 
 
3. Automatic notification of SECBCI clinical team. 
 
4. The research team to contact the caregiver and complete 
a semi-structured interview and the Caregiver & 
Environment Assessment for Neuropsychiatric 
Symptoms. 
 
5. The research team member documents findings and 
notifies PI and SECBCI clinical team.  
 
BCN Triggered 
Free Response 
Follow Up 
Questions 
 
1. Please describe the behavior or symptom that is most 
distressing to you. 
 
2. What about this behavior or symptom makes it 
distressing to you? Why is it distressing? 
 
3. Please describe anything that you think may have led to 
the behavior or symptom. 
 
4. Describe anything you tried to address the behavior or 
symptom. Did it help? 
 
 
 
 
 
 
 
 
 
 
 

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Figure 1.  Flow Diagram for The MOMENT RCT   
 
 
Prior to  
Enrollment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initial Visit 
Time Point  
 
 
 
 
3-mo Visit  
Time Point  
 
 
 
Interim  
Analysis 
 
 
 
Final Visit 
(6-mo) 
Time Point 
 
 
 
 
 
Initial screening for aMCI or AD participants and Caregiver Dyad from  
Sandra Eskenazi Center for Brain Care Innovation 
 
Complete Informed Consent/Assent, HIPPA Consent/Assent 
 
Total N: 308 participants  
(154 aMCI or AD subjects & 154 caregivers = 154 dyads) 
 
Perform baseline assessments 
(see section 8.0, Study Calendar) 
Install and demonstrate BCN app 
 
Final Assessments 
(see section 8.0, Study) 
BCN + Enhanced 
Care  
N = 154 (77 dyads) 
Perform 3-month assessments 
(see section 8.0) 
Interim Analysis conducted after 50% of participants (77 dyads) 
complete the study 
BCN + Enhanced 
Care  
N = 154 (77 dyads) 
Randomize 
1:1 Ratio 
Stratified on 
diagnosis, gender 
and age 

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6.0   Enrollment/Randomization 
6.1 
Patient Population and Setting: Our research center has 20 plus years of 
experience developing interventions to improve the care of older adults with AD and 
their caregivers. The PREVENT study applied the concepts of collaborative care to 
persons with AD in the primary care setting in a safety-net hospital system with in 
Indianapolis, IN43. At 12 and 18 months, results of the PREVENT study demonstrated 
improvements in BPSD frequency and caregiver distress from BPSD43. The results and 
experiences with PREVENT, as well as subsequent work by our research team and 
others led to the creation of the Sandra Eskenazi Center for Brain Care Innovation. This 
memory care practice serves as both a diagnostic and longitudinal care center for 
persons living with dementia and their family caregivers. 
 
6.2 
Preliminary Work: Neuropsychiatric Inventory Questionnaire (NPI-Q) – 
Ecological Momentary Assessment (EMA) Caregiver Pilot: We successfully pilot 
tested the NPIQ-EMA app in four AD patient-caregiver dyads without any attrition. The 
time horizon for the pilot differs from the proposal in that the caregiver was asked to fill 
out the smartphone survey (NPIQ-EMA) daily for a 2-week time period. Patient ages 
ranged from 63 to 95, and caregiver ages ranged from 63 – 82. Three of four caregivers 
identified as African American. All four caregivers found answering the NPIQ-EMA 
questions to “Not be burdensome.” Several caregivers reported that the NPIQ-EMA 
improved their awareness of the patient’s BPSD. Three of four answered that they 
would prefer weekly monitoring rather than daily and the last caregiver expressed a 
preference for daily monitoring. All caregivers agreed that the system was easy to use.  
 
6.3 
Recruitment, Screening, Informed Consent, and Enrollment: The Sandra 
Eskenazi Center for Brain Care Innovation provides longitudinal care to ~ 600 patients; 
38.7% are Black; and 70.4% are female. In addition, each of five clinicians completes 
an initial assessment on 1-3 new patients per week.  We anticipate a recruitment 
number of 154 dyads over 27 months and believe this to be achievable. Half of the 
dyads would be randomized to the intervention or treatment as usual group. Our group 
has a recruitment rate of approximately 50% of eligible subjects in this environment43.  
 
6.4 
Randomization Scheme: Participating dyads will be randomized to the two 
groups (intervention vs control) using a randomization list that contains group 
assignment in blocks, thus ensuring that the groups have comparable sample sizes 
throughout the study. We will use a stratified block random assignment following the 
Kernan strata determination formula (Kernan et al. 1999) listed as, # of strata < n / B x 
4, where B is block size and “…n is the sample size at the first planned interim analysis 
and 4 is a safety factor that accounts for unequal distribution of patients among strata.” 
Using n=154 and B=4, then, the # of strata < 9. In this study, we will use 8 strata = 2 
Diagnosis (aMCI, AD) x 2 Gender (M, F) x Age (< 65, ≥ 65). Sealed envelopes with 
randomization assignments will be prepared by a research team member not involved 

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with enrollment. Sealed envelope preparation will follow calculations and instructions 
made by the study biostatistician. 
 
Participants in the intervention group will be further randomly assigned to start with 1 of 
2 schedules of EMA surveillance frequency (1) weekly or (2) monthly. The intervention 
participants will then cross-over each month between the two surveillance frequency 
conditions, yielding 6 periods for their 2 x 6 cross-over design.  
 
 
6.5 
Potential Sources of Biological Variation and Co-variates: The experimental 
design allows us to explore moderators of response. 
 
  Table 3. Baseline Potential Sources of Variation 
Subject 
Obtained from caregiver 
Obtained from EMR 
aMCI/AD 
Subject 
Sex, age race, ethnicity, education level, 
medical status, insurance type  
Age, diagnosis, cognitive 
function, physical function, 
illness severity, problem 
list & med list  
Caregiver 
Subject 
Sex, age, race, ethnicity, education 
level, relationship to person with 
aMCI/AD, # of hours caregiving, 
caregiver burden, and perceived stress 
None 
 
 
7.0  
Study Procedures  
 Subjects will be identified from a list generated with patients who receive care at the 
Eskenazi Health, Sandra Eskenazi Center for Brain Care Innovation (SECBCI) and 
have a diagnosis of either Amnestic Mild Cognitive Impairment (aMCI) or possible or 
probable Alzheimer's disease (AD). Patients will also be referred by SECBCI 
providers. The screening portion of enrollment will be done either face-to-face in the 
SECBCI clinic or over the phone prior to the patient’s SECBCI appointment.  
 
 This study is seeking to recruit 154 patient-caregiver dyads (n=308 human subjects). 
 
Inclusion Criteria: 
1) The patient has received a diagnosis of Amnestic Mild Cognitive Impairment 
(aMCI) or probable or possible Alzheimer’s disease (AD) and receives his or her 
care at the Eskenazi Health, Sandra Eskenazi Center for Brain Care Innovation. 
2) The patient has a caregiver who is willing to participate in the study. 
3) The caregiver is at least 18 years of age and does not have visual impairment 
significant enough to interfere with the use of a smartphone.  
4) Both the patient and caregiver live in the community setting in Indiana. 
5) In cases where the patient with AD lacks capacity to consent to research, he or 
she must have a legally authorized representative (LAR) to consent on his or her 
behalf.  

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6) In cases where the patient lacks capacity to consent to research, he or she will 
be given an opportunity to provide assent. If the patient is unable to provide 
assent, an observable dissent will be honored. 
7) The caregiver reports having contact, in person, over the telephone or via video 
call with the patient with aMCI or AD at least weekly on average.  
 
Exclusion Criteria: 
1) History of serious mental illness (schizoaffective disorder, schizophrenia, bipolar 
disorder) 
2) The participant is participating in another caregiver intervention research study 
3) The participant lacks both the capacity to consent and a legally authorized 
representative (LAR) 
4)  
4.) The potential participant with a diagnosis of either aMCI or AD communicates 
observable dissent. 
5) 5.) The patient lives in a long-term care facility. 
 
 Using this research subject list the research team will access the patient electronic 
medical record to obtain contact information and other necessary screening data 
elements. This will be recorded on paper and destroyed as soon as the dyad declines 
interest in the study. If the subjects are enrolled in the study then this data will be 
inputted into a REDCap database. 
 
 Data Elements to be pulled from patient’s record prior to screening 
1) Patient name, DOB, MRN and contact information 
2) Primary caregiver name and contact information 
3) Diagnosis of either aMCI or possible or probable AD. 
4) Associated SECBCI physician name 
5) Most recent SECBCI visit date 
6) Next scheduled SECBCI visit date 
7) Most recent MMSE score and date 
 
 Once an eligible patient has been identified the study team member will notify the 
respective SECBCI provider, that their patient will be approached for recruitment and 
request their’ opinion of the patient's capacity to consent to research. The study team 
member will allow a week for the provider to respond before moving forward with 
contacting the patient-caregiver dyad. Only study team members will have access to 
the patient list. All study team members have completed CITI training. 
 The study team member will attempt to contact the patient-caregiver dyad by phone 
to see whether they would be interested in learning more about and possibly 
participating in the research study. A verbal recruitment screener will be used. 
 
 The study team member will explain the study and review the informed consent 
process. If both the patient and caregiver are interested they will proceed with 
scheduling a time for the patient-caregiver dyad to talk over the phone to conduct the 
informed consent review. At that time the research team member will mail out copies 

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of the informed consent and assent, the HIPAA authorization form, and the COVID-
19 risk handout. This handout will inform the patient and caregiver of the risks related 
to COVID-19 which should help them when making the decision to meet in person or 
complete the assessments over the phone.  
 
 The informed consent document and HIPAA authorization form will be reviewed over 
the telephone, rather than in-person, to minimize COVID-19 exposure. Once the 
participants have had time to ask questions and their understanding of the study is 
assessed, verbal consent will be attained. At this point in time, the study team 
member will ask the caregiver their appointment type preference, whether they want 
to meet in person the Eskenazi Health, Fifth Third Building or complete the 
assessments over the phone.  
 Before verbal consent is obtained, the patient will be assessed to determine their 
capacity to consent to research.  
o The provider reports the patient lacks the capacity to consent. 
o The MMSE score is </= 17 
 If neither of the aforementioned measures have been met, the 
study team will ask the patient the following 4 questions: 
 What do you understand is wrong with your brain health right 
now? 
 
 Can you please explain in your own words the choices I 
have presented to you (choice to consent)? 
 
 If you decide to participate in this study, what good things 
might happen and what harm might occur? 
 
 Can you please explain how you decided to participate (or 
not participate) in this study? 
 The determination to have the capacity to consent to research the 
patient must answer these 4 questions correctly.  
 The patient’s Legal Authorized Representative (LAR) will consent on the patient’s 
behalf if any of the following conditions are met: 
o The patient lacks the capacity to consent to research. 
o The patient is unable to communicate verbally or through another method 
due to the progression of their disease. 
o The patient has a court appointed guardian. 
As a part of the informed consent process, once capacity to consent has been 
established, the study team member will ask four teach back questions related to 
the study to both the caregiver and the patient. These questions are asked to 
ensure the caregiver and patient understand what they are consenting to, as well 
as making them aware that we have safety procedures in place to minimize their 
exposure to COVID-19. 
 
  If the caregiver chooses to complete the assessments remotely, the study team 
member will schedule a time to deliver study supplies. Regardless of what 

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randomization group they are in, the study team member will deliver a plastic bin 
which contains a binder with paper copies of the assessments and other study 
related materials. It will be delivered to the patient and caregiver’s respective homes 
without direct contact from team members (left outside home). If the dyad has been 
randomized to Group 2- The Three Assessments and Mobile Application and request 
to use a study mobile phone, this will be included in the plastic bin.  The purpose of 
the study binder is to ensure the dyad is able to follow along during the assessment. 
The study team members will have a mirror binder where they will indicate the 
caregiver’s responses to the assessment questions. 
 The study team member will then arrange a time for the caregiver to complete the 
baseline study visit. The baseline study visit will be completed over the telephone or if 
the caregiver prefers in-person at the Eskenazi Health, Fifth Third Building located on 
the Eskenazi Health Hospital Campus (the in-person visit is entirely optional). 
 
 The patient will not be present or participate in the baseline, 3-month or Final / 6-
month research visit. 
 
 
 During the informed consent visit, patients who have the capacity to consent will 
consent to the HIPAA authorization form, which grants the study team permission 
to access their Eskenazi Health medical record and to communicate with their 
SECBCI clinical team. If they do not have the capacity to consent, then their LAR 
will consent on their behalf. 
 The caregiver will also be asked to consent to a HIPAA authorization form as 
some of the assessments address their own personal health. In addition they will 
agree that data collected by the research team can be used for the purposes of 
research. 
 If consent by LAR is necessary, the study team will also seek a separate assent to 
participate from the individual with aMCI or AD. If an assent isn’t obtained, an audible 
dissent will be honored. 
 
 The patient with aMCI or AD will not receive any assessment or participate in 
interviews as their participation in the study is passive. Once enrollment of the patient 
with aMCI or AD is complete, they have completed their portion of the study. All other 
activities will involve the caregiver or the caregiver monitoring the patient with aMCI 
or AD. 
 
 Once enrollment is complete the study team member will schedule and conduct the 
baseline research visit with the caregiver and provide education to the caregiver 
about Behavioral and Psychological Symptoms of Dementia (BPSD). 
 
 If the participants choose to complete their assessment in person, then the study 
team member will call 24-48 hours before the baseline visit to make sure that in the 
past 2 weeks the patient and caregiver have not been in contact with anyone 
diagnosed with COVID-19, and have not developed any symptoms to suggest that 

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they currently have COVID-19. If they choose to complete their assessment over the 
telephone, then the study team will not make this call. 
 
 If either the patient or caregiver have had a recent COVID-19 exposure or symptoms 
of COVID-19 then the research visit will be rescheduled and the patient and/or 
caregiver will be referred to resources to help address the patient’s or caregiver’s 
COVID-19 exposure and/or symptoms.  
 
 The study team will follow Eskenazi Health policy by wearing a mask and gloves 
during any in-person research visit. 
  
 The study team will sanitize all research supplies and research visit space before and 
after every research visit.  
 
 The baseline visit includes completion of the following (+/- 14 days from 
enrollment ) and will be conducted over the phone or in-person at the Eskenazi 
Health, Fifth Third Building on the Eskenazi Health Hospital Campus. The in-
person visit option is entirely optional and is based on the caregiver’s 
expressed preference. COVID-19 safety and cleaning procedures are listed on 
page 22 of this protocol. Explanations that older adults and individuals with 
underlying health conditions are at greater risk for contracting COVID-19 and 
for having more severe health problems from COVID-19 if they contract the 
illness, including death, are outlined in the consent/assent: 
1) Single Item Literacy Screener (SILS) 
2) Motivations and Barriers Survey 
3) Dyad Demographics  
4) Neuropsychiatric Inventory Questionnaire (NPI-Q)  
5) Perceived Stress Scale 14 (PSS-14)  
6) Zarit Burden Interview (ZBI)  
7) COVID-19 Physical & Mental Health Questionnaire 
8) Senior Technology Acceptance Form 
9) Caregiver & Environment Assessment of Neuropsychiatric Symptoms (CEAN) 
10) Caregiver Pre-Intervention Semi-Structured Interview 
11) Provision of education on BPSD  
12) Provision of a $10 Kroger gift card to both the patient and caregiver following 
completion of the baseline visit activities. 
13) Provision of an Eskenazi Health parking voucher (only if the visit takes place in-
person). 
 
 
 
 
 The caregiver in the intervention group will be asked to complete a survey on 
Behavioral and Psychological Symptoms of Dementia (BPSD) for the person with 
aMCI or AD for 6 months through either the caregiver’s smartphone or a loaner 
smartphone from the study. The survey is a mobile health version of the 

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Neuropsychiatric Inventory – Questionnaire (NPI-Q) delivered by the Brain 
CareNotes (BCN) app. The following additional survey question well be asked 
following delivery of the NPI-Q, “How burdensome was completion of the prior scale? 
(Answer options: not at all burdensome, mildly burdensome, moderately 
burdensome, or extremely burdensome)” 
 
 
 Clinically Significant BPSD will be defined as when any NPI-Q severity domain = 
3 regardless of caregiver distress, or whenever NPI-Q caregiver distress is 
marked as “moderate”  “severe” or “very severe”. 
  
 
 When Clinically significant BPSD is present at either the baseline visit, 3-month visit, 
final (6-month) visit or through completion of a BCN app record then the following 
actions will be triggered: 
 
1) Automatic free response follow-up questions (via BCN). 
2) Automatic notification of study team. 
3) Automatic notification of SECBCI clinical team. 
4) The research team to contact the caregiver and complete a semi-structured 
interview and the Caregiver & Environment Assessment for Neuropsychiatric 
Symptoms. 
5) The study team member documents findings and notifies PI and SECBCI clinical 
team.  
 
 If the participants choose to complete their assessment in person then the study team 
will call 24-48 hours before the 3-month visit to make sure that in the past 2 weeks 
the patient and caregiver have not been in contact with anyone diagnosed with 
COVID-19, and have not developed any symptoms to suggest that they currently 
have COVID-19. If they choose to complete their assessment over the telephone, 
then the study team will not make this call. 
 
 The 3-month assessment visit occurs 3 months from their baseline completion 
(+/- 14 days) includes completion of the following, and will be conducted over 
the phone or in-person at the Eskenazi Health, Fifth Third Building on the 
Eskenazi Health Hospital Campus. The in-person visit option is entirely 
optional and is based on the caregiver’s expressed preference. COVID-19 
safety and cleaning procedures are listed on page 22 of this protocol. 
Explanations that older adults and individuals with underlying health 
conditions are at greater risk for contracting COVID-19 and for having more 
severe health problems from COVID-19 if they contract the illness, including 
death, are outlined in the consent/assent: 
1 
2)  
3)  
4) Neuropsychiatric Inventory Questionnaire (NPI-Q)  

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5) Perceived Stress Scale 14 (PSS-14)  
6) Zarit Burden Interview (ZBI)  
7) COVID-19 Physical & Mental Health Questionnaire 
8) Senior Technology Acceptance Form 
9) Caregiver & Environment Assessment of Neuropsychiatric Symptoms (CEAN) 
10) System Usability Scale (SUS) – only administered to the intervention group  
11) Caregiver Post-Intervention Survey – only administered to the intervention 
group 
12) Caregiver Pre-Intervention Semi-Structured Interview 
13) Provision of an Eskenazi Health parking voucher (only if the visit takes place 
in-person). 
 
 Clinically Significant BPSD will be defined as when any NPI-Q severity domain = 
3 regardless of caregiver distress, or whenever NPI-Q caregiver distress is 
marked as “moderate”  “severe” or “very severe”. 
 
 When Clinically significant BPSD is present at either the baseline visit, 3-month visit, 
final (6-month) visit or through completion of a BCN app record then the following 
actions will be triggered: 
 
1) Automatic free response follow-up questions (via BCN). 
2) Automatic notification of study team. 
3) Automatic notification of SECBCI clinical team. 
4) The research team to contact the caregiver and complete a semi-structured 
interview and the Caregiver & Environment Assessment for Neuropsychiatric 
Symptoms. 
 5) The study team member documents findings and notifies PI and SECBCI clinical 
team.  
 
 The study team will call 24-48 hours before the final / 6-month visit to make sure that 
in the past 2 weeks the patient and caregiver have not been in contact with anyone 
diagnosed with COVID-19, and have not developed any symptoms to suggest that 
they currently have COVID-19. 
 
 Final / 6-month visit occurs from the completion of their 6 month participation 
(+/- 14 days)  includes completion of the following, and will be conducted over 
the phone or in-person at the Eskenazi Health, Fifth Third Building on the 
Eskenazi Health Hospital Campus. The in-person visit option is entirely 
optional and is based on the caregiver’s expressed preference. COVID-19 
safety and cleaning procedures are listed on page 22 of this protocol. 
Explanations that older adults and individuals with underlying health 
conditions are at greater risk for contracting COVID-19 and for having more 
severe health problems from COVID-19 if they contract the illness, including 
death, are outlined in the consent/assent: 
1) Caregiver is asked to return the loaner phone or where personal phone is used 
the Brain CareNotes app will be uninstalled. 

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2) Neuropsychiatric Inventory Questionnaire (NPI-Q) 
3) Perceived Stress Scale 14 (PSS-14) 
4) Zarit Burden Interview (ZBI) 
5) Caregiver & Environment Assessment of Neuropsychiatric Symptoms (CEAN) 
6) COVID-19 Physical & Mental Health Questionnaire 
7) Senior Technology Acceptance Form 
8) System Usability Scale (SUS) – only administered to the intervention group 
9) Caregiver Post-Intervention Survey – only administered to the intervention group 
10) Caregiver Post-Intervention Semi-Structured Interview 
11) Provision of a $10 Kroeger gift card to the caregiver after completion of final visit 
activities. 
12) Provision of an Eskenazi Health parking voucher (only if the visit takes place in-
person). 
 
 Once the final visit has been completed and the caregiver has received the $10-dollar 
Kroger gift card for their time, participation in the study will be complete. 
 
 All semi-structured interviews will be audio recorded, stored securely, and 
transcribed. Once transcribed audio recordings will be destroyed. 
 
 For every remote assessment, baseline/ 3-month/ 6-month, the research team will 
follow the COVID-19 safety precautions, which includes donning proper PPE and 
cleaning procedures. 
o If the subject requests a remote assessment, the research team member 
delivers and retrieves the supply box; the team member will don gloves 
and a mask during the respective transaction. 
o If the team member has retrieved the supply box they will put the supply 
box into another plastic bin, and load it into the trunk of their car. It will 
remain there until they have the opportunity to sanitize the plastic supply 
box and supplies. 
o The research team members will wear gloves and use sanitizing wipes 
and/or a prepared bleach solution with paper towels. 
o They will dispose of contaminated materials into a plastic bag and throw it 
away. 
o Once all of the supplies have been sanitized, the research team member 
will wash their hands thoroughly for a minimum of 20 seconds. 
 
 For every in-person assessment, baseline/ 3-month/ 6-month, the research team will 
follow the COVID-19 safety precautions, which includes donning proper PPE and 
cleaning procedures. The research visits as well as the safety procedures have been 
reviewed and approved by Eskenazi Health. 
o If the subject is comfortable with being seen in person at the Fifth Third 
Building, the research team member will call the day before and the day of 
to screen the subject for any COVID-19 related symptoms.  
o If the subject responds “YES” then the assessment will be rescheduled. If 
the subject responds “NO” then they can proceed with the appointment.  

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o On the day of the appointment, the research team member will don a 
mask and wear gloves throughout the assessment. They will also request 
the subject wear a mask. If the patient/caregiver dyad doesn’t bring one 
with them or isn’t provided one upon arrival to Eskenazi Health, the study 
team will provide the mask for them. The dyad will also receive a parking 
voucher for their time spent with the research team member. 
o If the subject has a cough, that is not COVID-19 related, the research 
team member will be required to wear a gown and face shield. 
o All cleaning procedures remain the same. 
 
8.0 
Study Calendar 
A detailed table of study activities is listed below. 
 
  Table 4. Schedule of Study Activities 
Schedule of Study Activities 
 
Baseline 
Visit 
Within 14 
days of 
enrollment 
 
3-mo 
Within 14 
days of 
scheduled 
target date 
 
Final Visit 
(6-mo) 
Within 14 
days of 
scheduled 
end 
Provision of Study Information 
X 
 
 
Completion of Informed Consent and HIPAA 
Consent 
X 
 
 
Installation of BCN on loaner or caregiver phone  
X 
 
 
Provision of BCN instructions 
X 
 
 
Provision of Education on BPSD 
X 
X 
X 
COVID-19 Symptom Screener 
X 
X 
X 
Collect/Administer the following: 
 
 
 
COVID-19 Physical & Mental Health 
Questionnaire 
X 
X 
X 
Single Item Literacy Screener (SILS) 
X 
 
 
Dyad Demographics 
X 
 
 
NPI-Q 
X 
X 
X 
PSS-14 
X 
X 
X 
ZBI 
X 
X 
X 
Motivators and Barriers Survey 
X 
 
 
Caregiver Pre-Intervention and Phone Semi-
Structured Interview* 
X 
X 
X 
Caregiver & Environment Assessment of 
Neuropsychiatric Symptoms (CEAN)* 
X 
X 
X 
BCN app - Task Completion Burden Questions* 
X 
X 
X 
BCN app - Free Response Follow-Up Questions* 
X 
X 
X 
Data from EMR 
X 
X 
X 
Senior Technology Acceptance Scale 
X 
X 
X 

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System Usability Scale (SUS) 
 
X 
Intervention 
group only 
X 
Intervention 
group only 
Caregiver Post-intervention Survey 
 
X 
Intervention 
group only 
X 
Intervention 
group only 
Caregiver Post-Intervention Semi-Structured 
Interview 
 
 
X 
 
 
 
 
Loaner phone retrieved or BCN app uninstalled 
from the caregiver phone 
 
 
X 
Provision of a $10 Kroeger gift card to Caregiver 
X 
 
X 
Provision of a $10 Kroeger gift card to Caregiver 
X 
 
 
Provision of a parking voucher, only if visit is 
conducted in-person 
X 
X 
X 
   * Triggered by Clinically Significant BPSD  
 
 
9.0   
Collection and Reporting of Adverse Events and Serious Adverse Events 
The PI will comply with Indiana University IRB and the NIA guidelines for defining, 
collecting, and reporting serious adverse events (SAE), adverse events (AE), and 
unanticipated problems. 
 
9.1  
AE/SAE Definitions 
9.1.1 Classification of Severity, Expectedness and Study Relatedness 
Severity 
 Mild - Awareness of signs or symptoms, but easily tolerated and are of minor 
irritant type causing no loss of time from normal activities. Symptoms do not 
require therapy or a medical evaluation; signs and symptoms are transient. 
 Moderate - Events introduce a low level of inconvenience or concern to the 
participant and may interfere with daily activities, but are usually improved by 
simple therapeutic measures; moderate experiences may cause some 
interference with functioning 
 Severe - Events interrupt the participant’s normal daily activities and generally 
require systemic drug therapy or other treatment; they are usually incapacitating 
 
Expectedness  
AEs will be assessed as to whether they were expected to occur or unexpected, 
meaning not anticipated based on current knowledge found in the protocol, investigator 
brochure, product insert, or label. 
 
Categories 
 Unexpected - nature or severity of the event is not consistent with information 
about the condition under study or intervention in the protocol, consent form, 
product brochure, or investigator brochure. 

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 Expected - event is known to be associated with the intervention or condition 
under study. 
 
Relatedness 
The potential event relationship to the study intervention and/or participation is 
assessed by the PI with input from the study research coordinator. 
 
Categories 
 Definitely Related - The adverse event is clearly related to the investigational 
agent/procedure – i.e. an event that follows a reasonable temporal sequence 
from administration of the study intervention, follows a known or expected 
response pattern to the suspected intervention, that is confirmed by improvement 
on stopping and reappearance of the event on repeated exposure and that could 
not be reasonably explained by the known characteristics of the subject’s clinical 
state. 
 
 Possibly Related: - An adverse event that follows a reasonable temporal 
sequence from administration of the study intervention follows a known or 
expected response pattern to the suspected intervention, but that could readily 
have been produced by a number of other factors. 
 
 Not Related: - The adverse event is clearly not related to the investigational 
agent/procedure - i.e. another cause of the event is most plausible; and/or a 
clinically plausible temporal sequence is inconsistent with the onset of the event 
and the study intervention and/or a causal relationship is considered biologically 
implausible.  
 
9.2   
Protocol for AE/SAE Data Collection and Reporting  
All adverse events, unanticipated problems and potential risks will be monitored and 
collected ongoing and throughout the study by the study PI, research coordinator and 
research assistants. Events related to any patient and caregiver loss of privacy or 
confidentiality or discomfort, anxiety or distress related to completing the intervention or 
the outcome questionnaires will be assessed by the research assistant via monitoring of 
the BPSD and caregiver distress data reported by the caregiver via smartphone, by 
phone or face-to-face interactions and by patient and caregiver reports. 
 
For all participants, adverse events will be collected starting at enrollment and continue 
until after the participant has completed the study. If an adverse event occurs, it will be 
documented on the NIA adverse event and serious adverse event forms found at:  
https://www.nia.nih.gov/research/dgcg/clinical-research-study-investigators-
toolbox/adverse-events.  
 

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Unanticipated problems that do not meet the definition of an adverse event, will be 
documented in a study log that will be stored in a secure electronic folder behind the IU 
fire wall. Details in the log may include participant study ID, date that the problem was 
reported or discovered by the study, a description of the problem, and a corrective plan 
and measures to prevent reoccurrence. 
 
Measurement and Reporting of Adverse Events - Adverse events associated with 
monitoring of BPSD or caregiver distress related to AD are infrequent. Therefore, 
adverse event rates are expected to vary little between the two screening groups and 
control group. Adverse events will be monitored by the research coordinator on an 
ongoing basis. All adverse events and unanticipated problems will be reported to the 
study PI within 24 hours. We plan to present adverse events data to the DSMP safety 
officer when requested and at scheduled meetings. The NIA adverse event form will be 
used by the study staff to report all adverse events caused by the intervention.  
 
In the case of a participant death related to the intervention, the NIA Program Officer, 
the IU IRB and the Safety Officer will be notified within 24 hours using NIA standardized 
forms for reporting serious adverse events (noted above). If unanticipated, serious 
adverse events occur (i.e., not listed in the Data and Safety Monitoring Plan) and that 
are related to the intervention, they will be reported to NIA Program Officer, the IU IRB, 
and to the study Safety Officer within 48 hours of study’s knowledge of the event using 
NIA standardized forms for reporting serious adverse events. In cases where there is 
any question regarding the level of an adverse event or attributable cause, or areas of 
uncertainty, the study team and PI will consult with the Safety Officer and IU IRB. The 
summary of all other adverse events and unanticipated problems should be reported to 
NIA Program Officer and to the Safety Officer semi-annually, unless otherwise 
requested. 
 
 
10.0 Data Safety Monitoring 
The data safety monitoring plan (DSMP) for this trial will be monitored by the PI and a 
Safety Officer from an outside institution. The Safety Officer will act in an advisory 
capacity to the IU IRB and NIA Program Officer to monitor participant safety, evaluate 
the progress of the study, to review procedures for maintaining the confidentiality of 
data, the quality of data collection, management, and analyses. 
 
10.1 Frequency of Data and Safety Monitoring 
The Safety Officer and the PI will meet by teleconference initially to review and approve 
the study protocol and DSMP. Following that initial meeting, the Safety Officer and the 
PI will meet twice annually, either in person or by teleconference, to review study 
progress, data quality, and participants’ safety. The first DSMP review will occur six 
months after approval to begin recruitment.  Reporting will include subject accrual, 
adverse event rates, subject complaints, compliance to interventions, and protocol 
violations/noncompliance. Thereafter, the PI and Safety Officer review will occur every 
six months and review of adverse events reports will occur as summarized in table 5. 
 

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 Table 5. Safety Officer Reporting 
Frequency of Review 
 
Each 
Occurrence 
Quarterly 
Semi-
Annually 
Subject accrual (adherence to 
inclusion/exclusion); drop-out rates; 
randomization 
 
X 
X 
Serious adverse events (e.g. death) 
X 
X 
X 
Adverse events  
 
X 
X 
Subject Complaints 
 
X 
X 
Compliance with Intervention 
 
X 
X 
Protocol Violation/Non-compliance 
 
X 
X 
Stopping rules report 
X 
 
X 
 
The PI is responsible for collecting and recording all study data and ensuring 
participants safety on a daily basis. Adverse events, will be monitored on an ongoing 
basis by the study research assistant and PI. All adverse events and unanticipated 
problems will be reported to the study PI within 24 hours. In the case of a participant 
death related to the intervention, the NIA Program Officer, the IU IRB and the Safety 
Officer will be notified within 24 hours. If unanticipated, serious adverse events occur 
(i.e., not listed in the Data and Safety Monitoring Plan) and that are related to the 
intervention, they will be reported to NIA Program Officer, the IU IRB, and to the Safety 
Officer within 48 hours of study’s knowledge of the unanticipated serious adverse event. 
In cases where there is any question regarding the level of an adverse event or 
attributable cause, or areas of uncertainty, the study team will consult with the Safety 
Officer and IU IRB. The summary of all other serious adverse events should be reported 
to NIA Program Officer and to the Safety Officer semi-annually, unless otherwise 
requested by the Safety Officer. 
 
10.2 Content of Data and Safety Monitoring Report 
The research coordinator and study biostatistician will generate data and safety 
monitoring reports for PI and the Safety Officer that will contain: 
 
a) Summary of adverse events and an explanation of how each event was handled, 
b) Summary of complaints and how each complaint was handled, 
c) Subject retention, including the number and reasons of participant withdrawals, 
and study quality 
d) Intervention compliance (session attendance), and 
e) Summary of protocol violations and how each was handled. All reports will be 
submitted to IU IRB at time of continuing review. 
 
10.3 Safety Officer Affiliation 
The Safety Officer will be determined after the NIA review of the proposed study DSMP. 
The Safety Officer will be reviewed and approved by the NIA. Should there be any 
questions regarding the independence of the Safety Officer, they will be addressed and 
corrected if necessary at that time. 
 

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10.4 Conflict of Interest for Safety Officer 
The Safety Officer will not have a direct involvement with the study or conflict of interest 
with the investigators or institutions conducting the study. The Safety Officer will 
complete COI forms that report all financial interests such as salary, consulting and / or 
speaker fees, honoraria, research support, equity interests (e.g., stocks, stock options, 
or other ownership interests), and intellectual property rights (e.g., patents, copyright 
and royalties from such rights). 
 
10.5 Protection of Confidentiality 
Data presented at the PI and the Safety Officer semiannual meeting, the Safety Officer 
Reports, and discussions at the meeting will be kept confidential. Participant identities 
will not be known to the Safety Officer 
 
10.6 Safety Officer Responsibilities 
In summary, the Safety Officer will meet with the PI by teleconference or in person, 
initially to review and approve the protocol and DSMP, and then will meet semi-annually 
to review study progress, data quality, and participants’ safety. Reporting will include 
subject accrual, adverse event rates, subject complaints, compliance to interventions, 
and protocol violations/noncompliance. Other Safety Officer responsibilities include: 
 Review the research protocol, informed consent documents, plans for data 
safety and monitoring, and Manual of Procedures; 
 Recommend subject recruitment be initiated after receipt of a satisfactory 
protocol; 
 Evaluate the progress of the trial, including periodic assessments of data 
quality and timeliness, recruitment, accrual and retention, participant risk 
versus benefit, performance of the trial sites, and other factors that can affect 
study outcome; 
 Consider factors external to the study when relevant information becomes 
available, such as scientific or therapeutic developments that may have an 
impact on the safety of the participants or the ethics of the trial; 
 Review study performance, make recommendations and assist in the 
resolution of problems reported by the Principal Investigator; 
 Protect the safety of the study participants; 
 Report to NIA on the safety and progress of the trial; 
 Make recommendations to the NIA and the Principal Investigator concerning 
continuation, termination or other modifications of the trial based on the 
observed beneficial or adverse effects of the treatment under study; 
 If appropriate, review data in accordance with stopping rules, which are 
clearly defined in advance of data analysis. 
 Ensure the confidentiality of the study data and the results of monitoring; 
and, 
 Assist the NIA by commenting on any problems with study conduct, 
enrollment, sample size, and/or data collection. 
10.7  Stopping Rules 

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To ensure the integrity of the data, our study biostatistician will perform monthly cross 
tabulations of the data to confirm that each data field is being filled properly. It is unlikely 
that the study would be stopped early due to important favorable differences in the 
intervention group compared to control group because of the nature of the intervention 
and outcome measures. However, the study could be stopped early due to adverse 
events. Some events of particular concern would be a high number of study withdrawals 
due to discontent with the study procedures. The IU IRB and/or NIA Program Officer will 
make the final decision on whether or not to accept the Safety Officer’s 
recommendation about discontinuation of any component of the study. 
 
10.8 Limits of Assumptions 
It is possible that baseline differences between the groups, excessive study dropouts 
and/or missing data by the interim measurement time point (midway point to targeted 
enrollment) will limit the value of data analysis of measurements. Baseline differences 
will be evaluated after the first measurement time point and effects on the power to 
detect differences in the primary outcome will be evaluated and communicated by the 
study biostatistician to the PI and Safety Officer. Given the monitoring plans outlined, it 
is exceedingly unlikely that there will be baseline differences between groups of any 
magnitude to threaten the validity of the study. 
 
 
11.0 Study Withdrawal/Discontinuation 
Participants can decide to withdraw from the study at any time.  The study team will 
help the participant safely withdraw from the study.  
 
To withdraw from the study the participant must either contact the principal investigator 
Dr. Daniel Bateman, MD by phone (317) 963-7326 (voicemail) or in writing 
darbate@iupui.edu (email) or address: Daniel Bateman, MD, IU Department of 
Psychiatry, Suite 2800, 355 West 16th Street, Indianapolis, IN 46202 
 
If they cannot reach Dr. Bateman during his regular business hours (i.e. 8:00AM-
5:00PM), they can call the IU Human Subjects Office at (317) 278-3458 or (800) 696-
2949. 
 
There are no expected risks for early withdrawal from the study. 
 
12.0 Statistical Considerations and Analysis 
12.1 AIM 1: Quantitatively and qualitatively, determine the feasibility of collecting 
responses on an EMA version of the Neuropsychiatric Inventory Questionnaire (NPIQ-
EMA) from caregivers using smartphone technology at differing frequency intervals 
weekly or monthly, or a control group with data collected without the mobile health 
version and only at baseline and 6 month).  
 

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H1: Caregivers in the intervention groups will complete the assessments via 
smartphone and report an acceptable response burden. We anticipate that the 
response burden will be comparable to data collected in routine office visits. 
 
Analysis H1: The primary outcomes for AIM 1 are feasibility and usability.  
Feasibility will be measured 5 different ways:  
1) Completion rate of the NPIQ-EMA over 6 months 
2) Answers to the NPIQ-EMA response burden question every time the NPIQ-EMA 
is completed: “How burdensome was completion of the prior scale (Answer 
options: not at all burdensome, mildly burdensome, moderately burdensome, or 
extremely burdensome)” 
3) Completion rate of the semi-structured phone interviews triggered by “clinically 
significant” symptoms 
4) Post-intervention survey (quantitative)   
5) Post-intervention semi-structured interview (qualitative) occurring immediately at 
the end of 6 months.  
 
Usability will be measured in 3 different ways post-intervention:  
1) System usability scale (SUS) total score 
2) Post-intervention survey (quantitative) 
3) Semi-structured phone interview (qualitative).  
 
Quantitative Analysis: For quantitative analyses, there scores are continuous scale 
scores. Therefore, the intervention group feasibility scores will be compared to the 
control group’s feasibility (response burden question) relative using ANCOVA to adjust 
for baseline characteristics including baseline demographics. The adjustment for 
baseline will increase precision and will statistically ensure comparability of the baseline 
level symptoms, even though random assignment should generally provide approximate 
comparability across a host of baseline characteristics.  
 
Qualitative Analysis: We will interpret the post-intervention semi-structured interview 
feasibility and usability questions with the thematic analysis methodology developed by 
Braun and Clarke44. We will take an inductive approach searching for observed patterns 
and working to develop theories for these findings44. Reflexivity journals, subjective 
reflections of the investigators interpretation of emerging findings,  will be used to help 
account for differences in investigator biases, values and judgments45,46. Expected 
outcomes regarding feasibility and usability will inform app development for AD 
caregivers in the future. 
 
12.2 AIM 2: Determine whether more frequent surveillance of BPSD yields more 
actionable data.  
 
H2: We expect there to be more occurrences of actionable data in the groups (i.e., 
intervention vs control) or conditions within a group (i.e., weekly vs monthly condition 
within the intervention group) that have more frequent monitoring. 
 

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Analysis H2: We define actionable data as data that could lead to a change in care 
plan. This was operationalized by setting “clinically significant” thresholds for NPI-Q 
symptoms and caregiver distress (see research design and methodology overview) that 
when reached led to contact and interval assessment between the research team and 
the caregiver. We will compare groups and conditions on the percentage of participants 
in each group or each condition that met at least one “clinically significant” threshold per 
month.  
 
A between-group test, using mixed nonlinear models to adjust for baseline covariates, 
will be used to compare the intervention group to the control group. A within-group test, 
using mixed nonlinear models to adjust for baseline covariates as well as the period 
effect (i.e., months 1-6) and the randomized condition (i.e., assigned to start with weekly 
vs monthly surveillance frequency), will be used to compare the two surveillance 
conditions (measured weekly or monthly depending on the month period) within the 
intervention group in a 2 x 6 cross-over analysis.  
 
12.3 AIM 3: Explore whether different surveillance intervals are associated with 
greater improvement in BPSD and CG distress. 
 
H3: Groups or conditions within a group that receive more frequent surveillance paired 
with response to “clinically significant” symptoms will have greater improvement in 
BPSD and in caregiver distress. 
 
Analysis H3: The change in rating of BPSD calculated by the difference in NPI-Q total 
scores and caregiver distress calculated by the difference in NPI-Q caregiver distress 
total scores at time of baseline assessment, 3 months and 6 months of the intervention 
group will be compared to the control group during the same time intervals. For this 
comparison we will use a between-group test, using mixed linear models to adjust for 
baseline covariates and to adjust for the baseline measure of the response variable 
(i.e., baseline NPI-Q total score or NPI-Q caregiver distress total score), will be used to 
compare the intervention group and control group on the repeated measured follow-up 
response variables (i.e., follow-up NPI-Q total score or NPI-Q caregiver distress total 
score). Separate models will be run for the NPI-Q total score and NPI-Q caregiver 
distress total score. A within-group test, using mixed linear models to adjust for baseline 
covariates and to adjust for the baseline measure of the response variable (i.e., 
baseline NPI-Q total score or NPI-Q caregiver distress total score) as well as the period 
effect (i.e., months 1-6) and the randomized condition (i.e., assigned to start with weekly 
vs monthly surveillance frequency), will be used to compare the two surveillance 
conditions (measured weekly or monthly depending on the month period) within the 
intervention group in a 2 x 6 cross-over analysis. We will also use these linear mixed 
models to perform the same type of between-group and within-group analyses in which 
the dependent variables are the following secondary variables: Perceived Stress Scale-
14, and Zarit Burden Interview. 
 
12.4 Power Justification and Analysis: The study was designed to have a power of 
80% for two-tailed tests with a significance of 5%.  

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In the original power justification, we used a Cohen’s d effect size of 0.65, which is 
between a medium (0.50) and a large (0.80) effect size. This was done primarily 
because of budgetary constraints associated with the K23 funding mechanism, which 
limited our ability to detect effect sizes smaller than 0.65 by enrolling beyond the 
proposed 96 dyads. However, with additional institutional funding support for 40% RA 
effort over 30 months we are now able to accommodate an enrollment sample size of 
154 dyads (77 in each group), resulting in a projected 64 analyzable participants in each 
arm (control and intervention) after accounting for an attrition rate of 17% seen in the 
previously noted in the protocol trial (Callahan et al., 2006; Calculation = (64 X 2)/0.83 = 
154). The analyzable sample of 64 per arm for two-tailed tests of two independent 
populations will provide 80% power (using alpha = 0.05) to detect a medium effect size 
of 0.50, which is a common effect size chosen in both R01 and K-series proposals. The 
power for paired within-group tests between weekly vs monthly conditions for the 64 
analyzable intervention participants will be slightly greater than 80% power. Selecting a 
medium effect size of 0.50 matches the effect size seen in the aforementioned non-
pharmacologic protocol trial, where effect sizes for total NPI score and NPI caregiver 
distress score improvements at 12 months were 0.502 and 0.568, respectively 
(Callahan et al., 2006). We expect that this would require approaching 12 dyads per 
month and consenting and enrolling 6 dyads per month (1-2 dyads per week) over a 
span of 30 months.  
 
The SECBCI practice employs 6 physicians each with a half day clinic where they see 
between 4 and 9 patients on any given half day. Meaning that a range of 24 – 54 total 
patients are seen per week, with over one third of patients carrying a diagnosis of AD, 
leading to projections of between 8 – 18 eligible patients per week. Our prior work has 
consistently shown a recruitment rate of 50% for eligible patients, meaning that it would 
be reasonable to expect a maximal consent and enrollment rate of 4 – 9 subjects per 
week, a number much greater than the required study recruitment number of 1 – 2 
subjects per week.  
 
12.5 Interim Analysis 
The interim analysis will be conducted following completion of the study by 77 patient-
caregiver dyads (half-way point) for safety and efficacy monitoring. At this time, adverse 
events, drop-out rates, and missing data will be reviewed in entirety. Stopping rules will 
be applied when appropriate. The interim analysis will take place with the involvement 
of the Research Coordinator, Study Biostatistician, Safety Officer, and PI. The decision 
to continue the study must be unanimous among these 4 parties.  
 
 
13.0 Data Management 
The Regenstrief Institute has the capacity to safety collect and secure research and 
clinical data, and a long track record of doing so. To minimize the risk of breach of 
confidentiality, all study materials will be regarded as strictly confidential. Paper study 
documents will be stored in a locked filing cabinet in a secure office at the Regenstrief 
Institute, IU Center for Aging Research. Data will be extracted into a pre-designed 

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REDCap database stored behind the IU firewall. The study team will not collect any 
additional data without the consent of the participant and the Indiana University IRB. 
Computerized data entry and data storage systems are password protected and will be 
accessible only to study personnel.  
 
Additionally, each participant will be given a unique identifier. Their data will be stored 
only using the unique identifier. A key that matches the unique identifier with identifiable 
data (name, dob, mrn) will be stored securely behind the IU firewall. All research study 
personnel have completed training in Human Subjects Research and HIPAA standards. 
 
Screening data obtained from EMR and phone calls will be collected on paper, stored in 
a secure office and locked file cabinet in the Regenstrief Institute, Inc. In the instance a 
potential participant refuses enrollment, the paper document with screening data will be 
destroyed. 
 
Participant data entered by the participant into the mobile application (BCN intervention) 
will be stored on an Amazon Web Services, HIPAA secure server and transferred into a 
secure REDCap database located behind the Indiana University Firewall.  
 
Participants will be asked to give consent to have their interviews recorded. Audio 
recordings will be transcribed into an electronic word document form. Both the audio 
recordings and word document will be stored on a secure Regenstrief Institute. Once 
transcribed audio recordings will be destroyed. 
 
13.1 Protection Against Study Risks 
We will only approach potentially eligible patients and caregivers. Both members of the 
dyad or a legally authorized representative (LAR) need to consent to participate in the 
study. The PI will be available to clarify any questions and offer any needed consultation 
during the consent process or data collection process. Participants will be informed that 
representatives of the IRB or other regulatory bodies may inspect their study records to 
verify the information collected and that all information will be handled in strictest 
confidence. All analyses from the study will be performed and reported in aggregate and 
will exclude any personally identifying information.   
 
To minimize potential anxiety on the part of patients or their family members, we will 
emphasize that participation is completely voluntary, that all information will be regarded 
as confidential, and that the subjects do not have to answer any questions they are 
uncomfortable answering. To minimize the risks that our intervention would have any 
negative impact on the dyad, we will monitor caregiver reporting of BPSD and caregiver 
stress, and burden of answering questions.  
 
Additionally, if the patient’s SECBCI treating physician objects to any patient’s 
participation in the study because they believe it may have a negative impact on care 
may refuse to allow us to contact the subject to participate.  
 
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database by study team prior to moving to production mode, 2) monthly audits of data 
entry into the REDCap database while the study is active and strict adherence to the 
proposed study protocol confirmed by audits of study team assessments. 
 
 
14.0 Privacy/Confidentiality Issues 
A recruitment waiver has been requested, for several reasons: (1) the eligibility criteria 
for participation is specific enough that any other recruitment method would result in 
inadequate recruitment, (2) bringing an individual with aMCI/AD to a medical or 
research appointment can be stressful for both the patient and the caregiver and calling 
the patient-caregiver dyad prior to their SECBCI appointment to gauge their interest in 
research has the potential to reduce stress, by reducing unexpected events and 
planning, 3) by allowing a recruitment waiver we will be able to receive the patient’s 
most recent mini-mental status exam (MMSE) score, a measure of dementia severity 
that will be used in part to judge whether the patient has capacity to consent to 
research, and (4) this will allow the research team to seek the patient’s SECBCI 
physician input to on whether or not he or she believes the patient to have capacity to 
consent to research.  
 
Without access to MMSE scores and physician input, there would need to be more 
extensive testing burdensome to the patient and caregiver to determine if the patient 
has capacity to consent for research. Screening data will be destroyed immediately after 
learning that the patient-caregiver dyad declines interest in the study or declines study 
enrollment and for those who consent to the study screening data will be destroyed 
immediately following enrollment. 
 
With the exception of screening information that will be destroyed if the patient-
caregiver declines interest in the study, no data included in the study will be recorded 
without the consent of the patient-caregiver dyad. During the baseline research visit 
(point of consent), throughout the 6-month study, including the 3-month visit and the 
final visit, the caregiver will be asked questions about dementia, stress, coping and 
about difficult behaviors and psychiatric symptoms of dementia. It is possible that some 
of these questions could cause anxiety or discomfort. To minimize risk the caregiver is 
made aware that these types of questions will be asked ahead of time. The caregiver is 
also given the option to not answer the questions or to stop at any time.  
 
As a part of the informed consent the caregiver-dyad will be asked to give consent for 
investigators to look at the patient's SECBCI medical records. There is the possibility 
that there could be a loss of confidentiality. We will minimize this risk by following the 
Regenstrief Institute, Indiana University Center for Aging Research data management 
and quality assurance practices as a method to mitigate risk for loss of confidentiality.  
 
Additionally, each participant will be given a unique identifier. Their data will be stored 
only using the unique identifier. A key that matches the unique identifier with identifiable 
data (name, dob, mrn) will be stored securely behind the IU firewall. All research study 
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15.0 Follow-up and Record Retention 
The duration of the study will last for 5 years (6 months per each subject) or when 
enrollment and study activities of 154 patient-caregiver dyads is complete, whichever 
happens first. Paper data and electronic data will be kept for 5 years, at which point 
paper-based data will be securely destroyed in line with standard Regenstrief Institute 
procedures.   
 
 
16.0 Other 
16.1 Essential Equipment: We will use the Android Pixel phone by Google as a 
loaner phone for study subjects (caregivers) who do not have their own smartphone. 
The phone will be pre-loaded with the EMA version of the NPI-Q delivered by mobile 
app. 
 
16.2 Potential Problems and Alternative Strategies:  
16.2.1 Worsening caregiver burden: One concern of this proposal, is whether EMA 
monitoring of BPSD creates too much of a burden on the already burdened caregiver. 
Participants in our 28-day R01 study and in our pilot have not found the EMA pinging of 
the smartphone to be burdensome. The R01 study population demographics overlap 
significantly with our anticipated patient-caregiver population. As a safeguard, we will 
use usability and burden questions from the semi-structured interview from the initial 10 
aMCI/AD caregiver-dyads to determine if the burden of answering EMA questions for 
the caregivers is too great. If that does turn out to be the case we will consider 
lengthening the surveillance interval or shortening the assessment battery.  
 
16.2.2 Drop off in participation during the monthly response interval: It is possible 
that participation in the EMA BPSD surveillance might drop off during the two-month 
block, where BPSD surveillance takes place monthly instead of weekly. To address the 
potential, drop off in participation during the monthly surveillance block we will observe 
attrition rates for our first 10 dyads. If attrition rates exceed that of 17% we will make an 
adjustment to surveillance frequencies dropping the monthly surveillance block and 
instead continuing with weekly surveillance.  
 
16.3 Summary and Future Directions: The following study looks to improve the care 
of aMCI/AD patient-caregiver dyads through the study of a BPSD surveillance 
intervention. Our choice of a weekly/monthly frequency, was a conservative approach in 
this early work to manage caregiver and provider burden but should evidence indicate 
high feasibility and value of weekly intervals, a future project could test higher 
frequencies to identify a frequency of diminishing return. Findings from this study will be 
used to develop a BPSD surveillance EMA intervention for a future R01 proposal that 
will improve the access to care and health of AD patient-caregiver dyads. This work will 
help my maturation into an independently funded investigator. 
 
 

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