The Canadian Therapeutic Platform Trial for Multidomain Interventions to Prevent Dementia: Brain Health Support Program Intervention
Phase: NA
Conditions: Dementia Prevention, Mild Cognitive Impairment, Subjective Cognitive Impairment, Cognitive Change
Sponsor: Baycrest

Protocol Title:
The Canadian Therapeutic Platform Trial for Multidomain Interventions to 
Prevent Dementia: Brain Health Support Program Intervention
NCT: NCT05347966
Document Title: Protocol
Document Date: April 17, 2023

Protocol Title: 
The Canadian Therapeutic Platform Trial for Multidomain Interventions to 
Prevent Dementia: Brain Health Support Program Intervention 
Protocol Acronym: 
CAN-THUMBS UP or CTU: BHSP 
Sponsor: 
The Canadian Consortium for Neurodegeneration in Aging 
Protocol Version: 
V4.0: 17APR2023 
Executive Lead: 
Howard Chertkow, MD, FRCPC, FCAHS 
Chair in Cognitive Neurology and Innovation and Senior Scientist, 
Baycrest and Rotman Research Institute 
Director, Kimel Centre for Brain Health and Wellness and Clinical Trials 
Unit, Baycrest 
Scientific Director, Canadian Consortium on Neurodegeneration in Aging 
Baycrest 
3560 Bathurst Street,  
Toronto, ON M6A 2E1 
Co-Principal  
Investigators: 
Howard Feldman, MDCM, FRCP(C) 
Director, Alzheimer’s Disease Cooperative Study 
Professor, Department of Neurosciences 
Dean, Alzheimer’s Disease and Neurodegenerative Research 
University of California, San Diego 
9500 Gilman Drive, MC 0949 
La Jolla, CA 92037-0949 
Haakon B. Nygaard, MD, PhD 
Assistant Professor, Division of Neurology 
Charles E. Fipke Professor in Alzheimer’s Research 
Director, UBCH Clinic for Alzheimer Disease and Related Disorders 
Staff Investigator, Djavad Mowafaghian Centre for Brain Health 
The University of British Columbia 
2215 Wesbrook Mall, Rm 5637 
Vancouver, BC V6T 1Z3 
Sylvie Belleville, Ph.D., MACSS FCAHS 
Canada Research Chair, Cognitive Neuroscience of Aging and 
Brain Plasticity 
Scientific Director, Centre de recherche de l’Institut Universitaire de gériatrie 
de Montréal 
CIUSSS du Centre-Sud-de-l’Île-de-Montréal 
Professor, Department of Psychology 
Université de Montréal 
4565, Chemin Queen-Mary 
Montréal, QC H3W 1W 

 
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Confidentiality Statement 
 
The information in this document contains information that is privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable laws and regulations. In any 
event, persons to whom the information is disclosed must be informed that the information is 
privileged or confidential and may not be further disclosed by them. These restrictions on 
disclosure will apply equally to all future information supplied to you, which is indicated as 
privileged or confidential. 
 
Manuel Montero-Odasso, MD, PhD, FRCPC 
Professor of Medicine, Epidemiology and Biostatistics 
University of Western, Ontario, Canada 
Director, Gait and Brain Lab 
Parkwood Institute 
550 Wellington Rd,  
London, ON N6C 5J1 
 
 

 
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SIGNATURE PAGE 
 
(SIGNATURES ON FILE WITH COORDINATING CENTER) 
 
 
 
____________________________________________ 
Howard Chertkow, MD, FRCPC, FCAHS 
Chair in Cognitive Neurology and Innovation and Senior Scientist, 
Baycrest and Rotman Research Institute 
Director, Kimel Centre for Brain Health and Wellness and Clinical 
Trials Unit, Baycrest 
Scientific Director, Canadian Consortium on Neurodegeneration 
in Aging 
Baycrest, Toronto, ON 
 
 
 
 _________________    
  Date (MMDDYYYY) 
 
____________________________________________ 
Howard Feldman, MDCM, FRCP(C) 
Director, Alzheimer’s Disease Cooperative Study 
Professor, Department of Neurosciences 
Dean, Alzheimer’s and Neurodegenerative Research 
University of California, San Diego, CA 
 
 
 
_________________    
  Date (MMDDYYYY) 
 
____________________________________________ 
Haakon B. Nygaard, MD, PhD 
Assistant Professor, Division of Neurology 
Charles E. Fipke Professor in Alzheimer’s Research 
Director, UBCH Clinic for Alzheimer Disease  
and Related Disorders 
Staff Investigator, Djavad Mowafaghian Centre for  
Brain Health 
The University of British Columbia, Vancouver, BC 
 
 
 
 _________________    
Date (MMDDYYYY) 
 
____________________________________________ 
Sylvie Belleville, Ph.D., MACSS FCAHS 
Canada Research Chair in Cognitive Neuroscience of  
Aging and Brain Plasticity 
Scientific Director  
Centre de recherche de l’Institut Universitaire de  
gériatrie de Montréal 
CIUSSS du Centre-Sud-de-l’Île-de-Montréal 
Professor, Department of Psychology 
Université de Montréal, Montréal, QC 
_________________    
Date (MMDDYYYY) 
 

 
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____________________________________________ 
Manuel Montero-Odasso, MD, PhD, FRCPC 
Professor of Medicine, Epidemiology and Biostatistics 
University of Western  
Director, Gait and Brain Lab 
Parkwood Institute, London, ON 
 
 
_________________    
Date (MMDDYYYY) 
 
 
 
 
 

 
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Study Summary 
Title 
Canadian Therapeutic Platform Trial for Multidomain Interventions to Prevent 
Dementia (CAN-THUMBS UP or CTU): Brain Health Support Program 
Intervention 
Background 
& Rationale  
In Canada, it is estimated that there are currently over 500,000 older adults 
living with dementia [1]. It has been estimated that close to a third of 
dementia cases could be prevented by addressing modifiable risk factors 
including; physical inactivity, depression, and social isolation, metabolic and 
vascular risk factors, sensory loss, sleep problems, cognitive inactivity and 
poor diet [2].  Prior studies have also reported that even in the early stages 
of AD, older adults can benefit from formal educational programs about 
dementia [3]. Furthermore, web-based programs focusing on risks and 
protective factors have been found to improve dementia-related 
protection/risk profiles in middle-aged adults [4]. Participating in an online 
educational program could potentially increase participants’ dementia 
literacy, empowerment, general self-efficacy and engagement regarding 
ways to promote their brain health.  
 
The Canadian Therapeutic Platform Trial for Multidomain Interventions to 
Prevent Dementia (CAN-THUMBS UP, or CTU) is a comprehensive and 
innovative program aimed to develop, implement and evaluate an interactive 
and compelling online educational Brain Health Support Program (BHSP) 
intervention, called Brain Health PRO (BHPro), with potential to positively 
influence dementia literacy, lifestyle risk factors, and scale-up to reach the 
broader Canadian public; enroll and retain a community-dwelling Platform 
Trial Cohort (PTC) of individuals at risk of dementia; and support an open 
platform trial to test a variety of multidomain interventions that might further 
benefit individuals at risk of dementia. BHPro is a 45-week, multidomain 
web-based formal educational program which has been designed to increase 
dementia literacy, convey best available evidence for lifestyle changes that 
can mitigate dementia risk, and foster engagement toward one’s own brain 
health. The program was developed as a collaborative effort by CCNA 
investigators with recognized expertise in the program’s content areas, along 
with input from older-adult citizen advisors. Furthermore, this study will 
employ mobile technology, such as remote testing of cognitive function and 
wearable devices that track changes in activity and sleep patterns, to more 
readily evaluate compliance and effects of lifestyle interventions. 
 
Implementation of a fully remote online research protocol will provide an 
accessible approach to research in a setting where restrictions to in-person 
evaluations may continue to be imposed by COVID-19 and would allow 
research progress towards the goal of dementia prevention during 
challenges such as COVID-19. In addition to reaching more potential 
participants who can more easily join the program, this will help us achieve 
the important goal of reaching a broader geography with recruitment of 
participants across Canada irrespective of where they live.   

 
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Target 
Population 
All Participants: 
• Ages 60-85 
• Meets criteria for No Dementia and one of the following (according to 
CCNA criteria):  
 Cognitively Unimpaired (CU)  
 Cognitively Unimpaired plus Subjective Cognitive Impairment (CU + 
SCI)   
 Mild Cognitive Impairment (MCI)  
 
• AND Classified as being at increased risk of dementia based on at 
least one of the following: 
 First-degree family history of dementia 
 Self-Reported or documented current and/or history at midlife (45-
60) on any of the following risk factors: 
o Hypertension (documented Systolic Blood Pressure > 140 
mm Hg; OR physician diagnosis of hypertension; OR 
treatment for hypertension; OR other approaches to treatment 
(e.g. diet, exercise)) 
o Hypercholesterolemia (documented total cholesterol > 6.5 
mmol/L; OR physician diagnosis of hypercholesterolemia; OR 
treatment for hypercholesterolemia; OR other approaches to 
treatment (e.g. diet, exercise)) 
o 
Body Mass Index > 30 kg/m2 (derived from NIH Metric BMI 
Calculator) 
o 
Physical Inactivity (active is defined as engaging in a 
minimum of 20- 30 min of physical activity causing sweating 
and breathlessness, at least 2 times a week) 
 
Number of 
Participants 
n = up to 350 (enrolled from across Canada using centralized recruitment) 
Study Goal 
and Aims 
Overall Goal:  
To develop and evaluate a 45-week web-based Brain Health Support 
Program (BHSP) intervention, called Brain Health PRO (BHPro), focused on 
dementia literacy, self-efficacy and modifiable lifestyle risk factors. 
Participants will subsequently be part of a PTC and may be evaluated for 
eligibility to participate in interventional dementia prevention trials under 
separate protocols. 
 
Aims: 
A. Our primary aim is to evaluate within-person change in dementia 
literacy following participation in BHPro. 
 
B. To evaluate within-person change following participation in BHPro, 
including change in: 
 
i. 
Self-efficacy and attitudes towards dementia and its 
screening  
ii. 
Individuals’ modifiable risk factors 
iii. 
Cognition 

 
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iv. 
Physical activity and sleep quality as measured by 
actigraphy and electroencephalogram (EEG) wearable 
devices 
 
C. To evaluate BHPro in relationship to: 
 
i. 
Levels of engagement (i.e., number of chapters 
completed), thresholds of compliance, ratings of 
satisfaction, and dropout rates from the intervention 
ii. 
Levels of engagement in the program as a function of 
individual characteristics and risk profile  
iii. 
Levels of engagement as a moderator of within person 
change in outcomes. 
iv. 
Association between change in modifiable risk factors and 
change in cognition 
 
D. To develop a successful comprehensive national recruitment plan to 
fully enroll the PTC with engagement stakeholder groups including 
participants, citizen advisors, and community partners.  
 
Outcome 
Measures 
Primary Outcome Measure:  
 
A. The primary outcome will be change in dementia literacy following 
participation in the study, as measured by the Alzheimer’s Disease 
Knowledge Scale.  
 
Secondary Outcome Measures: 
 
A. Change in self-efficacy following participation in the study, as 
measured by the General Self-Efficacy Scale (GSE). 
 
B. To evaluate BHPro, as measured by: 
 
i. 
Engagement using the online program (e.g., percentage of 
chapters completed) 
ii. 
User satisfaction ratings and evaluation of usability and 
acceptance (System Usability Scale and Technology 
Acceptance Model Questionnaire) 
 
Exploratory Outcome Measures: 
 
A. Change in attitudes toward dementia following participation in the 
study as measured by Sections B and D of the Perceptions Regarding 
Investigational Screening for Memory in Primary Care (PRISM-PC).  
 
B. Change in modifiable risk factors following participation in the study, 
as measured by BHPro Lifestyle Risk Questionnaires.  
 
C. Cognition 

 
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i. 
Change in global cognition based on a composite score 
using the Neuropsychological Test Battery (calculated as 
average Z scores standardized to the baseline mean and 
standard deviation). 
ii. 
Change in the subdomains of memory, processing speed, 
and executive functions based on composite scores 
derived from the Neuropsychological Test Battery 
(calculated as average Z scores standardized to the 
baseline mean and standard deviation). 
iii. 
Change in performance based on “Burst” Cognitive 
Testing that addresses:  
o Within-person change in asymptote, daily variation 
and within-burst practice effects of “burst” cognitive 
testing 
o Between- and within-person factors including self-
rated emotional reactivity and its association with 
variation in cognitive performance over the BHPro 
intervention 
iv. 
Change in performance based on online self-administered 
cognitive testing with the Cogniciti Brain Health 
Assessment 
v. 
Change in modifiable risk factors and relationship to 
change in cognition  
 
D. National recruitment success will be measured by:   
 
i. 
Enrollment rates per month and year across regions with 
centralized and local recruitment strategies 
ii. 
Screen fail rate and reasons 
iii. 
Projected enrollment rates vs actual enrollment rates 
 
E. 
Change in levels of physical activity and sleep quality, as measured 
by actigraphy and EEG wearable devices. 
 
F. 
Saliva sample collection, to characterize the distribution of age 
adjusted polygenic hazard scores within the BHSP study group. 
  
Study Design 
& Statistical 
Approach 
This initial phase (Phase A) of CTU will be a prospective 12-month multi-
center longitudinal intervention study to evaluate a web-based educational 
BHSP, called BHPro, focused on dementia literacy, self-efficacy, and 
modifiable lifestyle risk factors. Participants will be individuals who are either 
cognitively unimpaired or have MCI with increased risk related to lifestyle risk 
factors. At the conclusion of the BHSP intervention, participants will continue 
in the PTC with the opportunity to consent and enroll in further multidomain 
intervention trials. 
 
Sample Size & Power: 

 
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With an initial t1 sample size of 350 participants and an anticipated 20-30% 
range of drop-out rates, we will have between 245 (with 30% dropout) and 
280 (with 20% dropout) completed participants at t2 (end of intervention). All 
calculations are for 80% power and 5% two-tailed alpha. We considered 
small (d=0.2) and medium (d=0.5) Effect Sizes for 4 different t1-t2 
correlations (rt1-t2) in the primary outcome variable: r=0.2, 0.3, 0.4 and 0.5. A 
final sample of n=280 will allow us to detect an ES ≥0.2 if rt1-t2≥0.3.  A final 
sample of n=245 will allow us to detect an ES ≥0.2 if rt1-t2≥0.4. We are aiming 
to recruit 50% women to allow for later stratification of analyses to assess for 
sex differences.  
 
Statistical Approach: 
In our one-group pretest-posttest design the major interest is within-person 
change in the primary and secondary outcomes over time (response 
variables) in the presence of one or more explanatory variables that are 
categorical or continuous. The data will be analyzed using a mixed model for 
repeated measures approach (MMRM). This approach will treat sites and 
participants as random effects, while observational time and their 
characteristics such as sex and age as fixed effects. Potential effect 
modifications will be examined using this MMRM approach with variable 
selection based on Akaike/Bayesian information criterion.  
 
A more detailed and formal statistical analytic plan (SAP) will be developed 
and finalized during the study. The SAP will include detailed descriptions for 
evaluating our study outcomes including BHPro, cognition, physical activity 
and sleep, and recruitment metrics. 
 
 
 
 

 
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    STUDY SCHEMATIC  
Phase A: Platform Trial Cohort and Brain Health Support Program Intervention 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Remote Screening  
E-Consent 
Clinical Dx Assessment:  
No Dementia 
 (CU, CU+SCI, MCI) 
Ages 60-85  
Dementia Risk: 
Family History, Lifestyle and 
Vascular Risk Factors 
 
Remote Baseline 
Neuropsychological 
Testing, Behavior and 
Functional Assessments, 
Saliva Collection for 
genomic analysis 
 
Personalized Profiles  
Risk, Compliance to BHPro, and Longitudinal 
Course 
Outcomes 
 Dementia literacy, self-efficacy, and attitudes 
toward dementia 
 Modifiable risk factors 
 Cognition 
 User engagement, usability, and acceptability 
 Levels of activity and sleep quality 
 Genomic risk modifiers 
 
Brain Health PRO 
 (BHPro) Intervention:  
• Online Modules and Lifestyle Risk Impact Surveys: 
 
Motivation, Self-Efficacy, Positive Health, Environment and 
Genetic risk 
 
Physical Activity 
 
Cognitive Engagement 
 
Diet 
 
Sleep 
 
Social and Psychological Health 
 
Vascular health  
 
Vision and Hearing 
• Goal Setting 
• Remote Assessments 
 
MyCogHealth “Burst” Cognitive Testing 
 
Cogniciti Brain Health Assessment  
 
Actigraphy and EEG recordings (activity and sleep monitoring) 
 
Tele-health follow-up 
 
 

 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS 
14 
1.0 INTRODUCTION 
16 
1.1 
BACKGROUND 
16 
1.2 
RATIONALE 
18 
2.0 STUDY DESIGN 
19 
3.0 STUDY GOAL AND AIMS 
19 
3.1 
OVERALL GOAL 
19 
3.2 
AIMS 
19 
4.0 OUTCOME MEASURES 
20 
4.1 
PRIMARY OUTCOME MEASURE 
20 
4.2 
SECONDARY OUTCOME MEASURES 
20 
4.3 
EXPLORATORY OUTCOME MEASURES 
20 
5.0 ETHICS AND REGULATORY CONSIDERATIONS 
21 
5.1 
GOOD CLINICAL PRACTICE 
21 
5.2 
INSTITUTIONAL REVIEW BOARD (IRB) / RESEARCH ETHICS BOARD (REB) 
21 
5.3 
ELECTRONIC INFORMED CONSENT PROCESS 
22 
5.3.1 
E-Consent Process 
22 
5.4 
PARTICIPANT CONFIDENTIALITY 
23 
5.5 
POTENTIAL RISKS AND BENEFITS ASSOCIATED WITH THIS STUDY 
23 
5.5.1 
Potential Risks 
23 
5.5.2 
Potential Benefits 
24 
6.0 RECRUITMENT 
24 
7.0 PATIENT SELECTION 
24 
7.1 
INCLUSION CRITERIA 
24 
7.2 
EXCLUSION CRITERIA 
25 
8.0 STUDY PROCEDURES 
25 
8.1 
STUDY VISITS 
25 
8.1.1 
Technology for Remote Study Visits 
25 
8.1.2 
Video Conference Screening (within 21 days prior to baseline) 
26 
8.1.3 
Remote Baseline Visit (+/- 2 weeks) 
27 
8.1.4 
Additional Remote Baseline Testing 
28 
8.1.5 
Month 3 Remote Follow-Up and Testing 
28 
8.1.6 
Month 6 Remote Follow-Up and Testing 
29 
8.1.7 
Month 9 Remote Follow-Up and Testing 
29 
8.1.8 
Month 12 Remote Visit 
29 
8.2 
    PLATFORM TRIAL COHORT (PTC) 
31 
8.3 
BRAIN HEALTH PRO (BHPRO) INTERVENTION 
31 
8.3.1 
Program Content 
31 
8.3.2 
Personalized Profiles on Modifiable Lifestyle Risk Factors 
32 
8.3.3 
BHPro Outcome Variables and Data Collection 
32 
9.0 STUDY PROCEDURE DESCRIPTIONS 
33 

 
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9.1.1 
Sociodemographics 
33 
9.1.2 
Medical/Surgical/Family History 
33 
9.1.3 
Hearing and Vision Assessment 
33 
9.1.4 
CAIDE Score 
33 
9.1.5 
Saliva Sample for Genomics Testing (Polygenic Hazard Score) 
33 
9.1.6 
Remote Neurological Exam 
34 
9.2 
ONLINE COGNITIVE TESTING 
34 
9.2.1 
Cogniciti Brain Health Assessment 
34 
9.2.2 
MyCogHealth App “Burst” Cognitive Testing 
35 
9.3 
PHYSICAL ACTIVITY AND SLEEP MONITORING 
35 
9.3.1 
Actigraphy 
36 
9.3.2 
EEG Recording 
36 
9.4 
DATA COLLECTION FROM OTHER CCNA STUDIES 
36 
10.0 STUDY-SPECIFIC INSTRUMENTS 
37 
10.1 
COGNITIVE MEASURES 
37 
10.1.1 Clinical Dementia Rating (CDR) 
37 
10.1.2 Logical Memory I and II 
37 
10.1.3 Montreal Cognitive Assessment (MoCA) 
37 
10.1.4 Neuropsychological Test Battery (NTB) 
37 
10.1.5 Cogniciti Brain Health Assessment 
40 
10.1.6 “Burst” Cognitive Testing 
40 
10.2 
BEHAVIORAL AND FUNCTIONAL MEASURES 
41 
10.2.1 COVID-19 Impact Survey 
41 
10.2.2 Generalized Anxiety Disorder 7-Item Scale (GAD-7) 
41 
10.2.3 Geriatric Depression Scale (GDS) 
41 
10.2.4 Lawton Brody Instrumental Activities of Daily Living (IADL) Scale 
41 
10.2.5 Mild Behavioral Impairment Checklist (MBI-C) 
42 
10.2.6 Research Satisfaction Survey 
42 
10.2.7 Sleep Disorders Questionnaire 
42 
10.3 
BHPRO OUTCOME MEASURES 
42 
10.3.1 Alzheimer’s Disease Knowledge Scale (ADKS) 
42 
10.3.2 The General Self-Efficacy Scale (GSE) 
42 
10.3.3 Perceptions Regarding Investigational Screening for Memory in Primary Care 
(PRISM-PC) 
43 
10.3.4 System Usability Scale (SUS) 
43 
10.3.5 Technology Acceptance Model Questionnaire 
43 
11.0 EARLY DISCONTINUATION PROCEDURES 
43 
12.0 ADVERSE EVENTS 
43 
12.1 
EVALUATION AND REPORTING OF ADVERSE EVENTS 
44 
12.2 
ASSESSMENT OF ADVERSE EVENTS 
44 
12.3 
COLLECTION AND REPORTING OF SERIOUS ADVERSE EVENTS (SAES) 
45 
13.0 STATISTICAL CONSIDERATIONS 
46 
13.1 
SAMPLE SIZE AND POWER 
46 
13.2 
ANALYSIS PLAN 
47 
13.2.1   Sex and Gender Analysis 
47 
14.0 RECORDING AND COLLECTION OF DATA 
47 

 
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14.1 
CASE REPORT FORM 
47 
14.1.1 Standardized Subject Demographic and Clinical-Research Meta-Data 
47 
14.1.2 Recordings of Remote Study Visits 
47 
14.1.3 BHPro 
48 
14.1.4 Online Cognitive Testing 
48 
14.1.5 Actigraphy and EEG Recordings 
48 
14.1.6 Genomics 
49 
14.2 
STUDY FILES AND PATIENT SOURCE DOCUMENTS 
49 
14.3 
RATER TRAINING 
49 
14.4 
RETENTION OF DATA 
50 
14.5 
QUALITY ASSURANCE/QUALITY CONTROL 
50 
14.6 
INCIDENTAL FINDINGS 
50 
15.0 PUBLICATIONS POLICY AND SHARING OF DATA 
50 
16.0 REFERENCES 
52 
17.0 APPENDICES 
55 
17.1 
APPENDIX 1: CLINICAL DIAGNOSTIC CRITERIA 
55 
17.2 
APPENDIX 2: SCHEDULE OF EVENTS 
57 
17.3 
APPENDIX 3: BHPRO LIFESTYLE RISK QUESTIONNAIRES 
60 
17.4 
APPENDIX 4: SAMPLE SIZE CALCULATION FOR ONE-GROUP PRE-TEST POST-
TEST DESIGN 
61 
17.5 
APPENDIX 5: CTU FLOW OF DATA FIGURES 
62 
17.6 
APPENDIX 6: OPTIONAL CARDIOPULMONARY SENSOR SUB-STUDY 
67 
 
 
 
 
 
 
 
 

 
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LIST OF ABBREVIATIONS: 
AD 
Alzheimer’s Disease  
ADKS 
Alzheimer’s Disease Knowledge Scale 
AE 
Adverse Event 
BHA 
Cogniciti Brain Health Assessment 
BHPro 
Brain Health PRO 
BHSP 
Brain Health Support Program 
BMI 
Body Mass Index 
BNT 
Boston Naming Test 
BVMT-R 
Brief Visuospatial Memory Test-Revised 
CAIDE 
The Cardiovascular Risk Factors, Aging, and Incidence of Dementia 
CCNA 
Canadian Consortium for Neurodegeneration in Aging 
CDR 
Clinical Dementia Rating  
COMPASS-ND 
The Comprehensive Assessment of Neurodegeneration and Dementia 
CRF 
Case Report Form 
CTU 
CAN-THUMBS UP 
CU 
Cognitively Unimpaired 
CWIT 
Color-Word Interference Test 
DCF 
Data clarification form 
DKEFS 
Delis-Kaplan Executive Function System 
DSM 
Diagnostic and Statistical Manual of Mental Disorders 
DSPC 
Data Sharing and Publications Committee 
ECG 
Electrocardiogram 
EEG 
Electroencephalogram 
GAD-7 
Generalized Anxiety Disorder 7-Item Scale 
GCP 
Good Clinical Practice 
GDS 
Geriatric Depression Scale 
HIPAA 
Health Insurance Portability & Accountability Act 
IADL 
Instrumental Activities of Daily Living 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ICMJE 
International Committee of Medication Journal Editors 
IRB 
Institutional Review Board 
LMM 
Linear Mixed Model 
LORIS 
Longitudinal Online Research and Imaging System 
MBI-C 
Mild Behavioral Impairment Checklist 
MCI 
Mild Cognitive Impairment 
MMRM 
Mixed Model for Repeated Measures 
MoCA 
Montreal Cognitive Assessment 
MRI 
Magnetic Resonance Imaging 
MTP 
Master Trial Protocol 
NACC 
National Alzheimer’s Coordinating Center 
NTB 
Neuropsychological Test Battery 
OPT 
Open Platform Trial 
PC 
Primary Care 

 
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PHS 
Polygenic Hazard Score 
PI 
Principal Investigator 
PIPEDA 
Personal Information Protection and Electronic Documents Act 
PRISM 
Perceptions Regarding Investigational Screening for Memory 
RBD 
REM Sleep Behaviour Disorder 
RCT 
Randomized Controlled Trial 
REB 
Research Ethics Board 
RLS 
Restless Leg Syndrome 
SAE 
Serious Adverse Event 
SAP 
Statistical Analytic Plan 
SCI 
Subjective Cognitive Impairment 
SFTP 
Secure File Transfer Protocol 
SRI 
Sunnybrook Research Institute 
SUS 
System Usability Scale 
SYNERGIC 
Synchronizing Exercises, Remedies in Gait and Cognition 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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1.0 
INTRODUCTION 
1.1 
Background 
The opportunity to delay or prevent up to 30% of dementia cases through the active 
management of modifiable risk factors, notably vascular, diet, activity, sensory, cognitive and 
social engagement, prior to dementia onset, is increasingly recognized as the most tractable 
and immediate approach to finding effective treatment and prevention with an enormous public 
health impact [5]. Furthermore, even a modest delay of one year in the onset of dementia has 
been projected to save the Canadian health care system $120 billion over the next 3 decades 
[6]. Priorities for public health and lifestyle interventions have included those that promote brain 
resilience and address modifiable risk factors, an approach that will be directed by personalized 
host profiles [7, 8]. To address this, the Canadian Therapeutic Platform Trial for Multidomain 
Interventions to Prevent Dementia (CAN-THUMBS UP or CTU) has been designed as a 
comprehensive and innovative program aimed to develop an interactive and compelling online 
Brain Health Support Program (BHSP) intervention, called Brain Health PRO (BHPro), with 
potential to positively influence dementia literacy, lifestyle risk factors, and scale-up to reach the 
broader Canadian public; enroll and retain a community-dwelling Platform Trial Cohort (PTC) of 
individuals at risk of dementia; and support an open platform trial to test a variety of multidomain 
interventions that might further benefit individuals at risk of dementia.  
 
Addressing long-term outcomes with combined interventions that address risk factor 
modification and potentially promote brain resilience, could advance the important goal of 
acquiring evidence to guide public health policy for dementia prevention [5, 9-11]. Our focus in 
this study addresses many of these elements including understanding personalized risk profiles 
and the role of education and training. As well, we create a framework that will enable ongoing 
testing of combination and multidomain interventions for dementia prevention with novel 
approaches and with legacy contributions for the Canadian public. 
 
The Role of Education and Engagement in Dementia Prevention 
Prior studies have reported that even in the early stages of Alzheimer’s disease (AD), older 
adults can benefit from formal educational courses on dementia and that they can improve their 
knowledge of the disease, with beneficial effects on their mood and self-efficacy [3]. 
Furthermore, web-based educational programs focusing on risks and protective factors have 
been found to improve dementia-related protection/risk profiles in middle-aged adults [4]. 
Engaging in an educational program could potentially increase participants’ dementia literacy, 
empowerment, general self-efficacy and engagement regarding ways to promote their brain 
health. Based on prior studies, this could have a positive risk reduction effect on its own while 
also improving participants’ readiness to change and increasing motivation to participate in 
further prevention of dementia studies.  
 
Personalized Risk Profiles and Remote Assessments 
In considering the path to successful multidomain lifestyle interventions key issues include 
tailoring approaches to personalized risk profiles, addressing individual preferences, and 
compliance with and fidelity to the intervention. It is now increasingly possible to mobilize 
technology to more readily evaluate compliance and effects of lifestyle interventions, through 
the incorporation of wearable devices that track changes in activity levels and sleep patterns, 
and through app-based remote testing of cognitive function using paradigms of ‘burst’ cognitive 
testing and/or self-administered online cognitive testing. These measurement approaches 
should be very informative in evaluating how interventions are being taken up and also in 

 
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assessing whether there is an early and subtle slope of decline. Such early detection of decline 
can be used to design more powerful, personalized trials where those at the highest predicted 
risk would be included and those at lower risk excluded. There is emerging evidence that 
lifetime cognitive activity can mitigate or forestall AD pathology specifically in genetically 
susceptible individuals, suggesting that tailoring cognitive training according to genetic risk is 
warranted in trying to achieve best outcomes [12]. Additionally, there is evidence that the 
intensity and supervision of lifestyle interventions, including exercise and cognitive training, 
contributes in part to their potential efficacy. Given the inherent cost and infrastructure needed 
for more intensive lifestyle interventions, including personal trainers, coaches and trained staff 
compared to self-administration [13, 14] it is important to enrich the targeted population to those 
at higher risk. Employing technology for remote data collection provides a timely opportunity to 
engage with participants and continue to advance research in dementia prevention in the 
context of current restrictions to traditional research conduct during the global novel coronavirus 
(COVID-19) pandemic. 
 
Dementia Risk Scores 
Significant progress has been made in identifying those at high risk of dementia with aging 
through testing that can be quite simply and readily undertaken. The Cardiovascular Risk 
Factors, Aging, and Incidence of Dementia (CAIDE) Score provides an age, metabolic, and 
vascular factor risk score and is a validated tool to predict late-life dementia risk  [15]. The 
Polygenic Hazard Score (PHS) is derived from analysis of a 31 single-nucleotide polymorphism 
(SNP) panel that has been demonstrated to reliably identify individuals at risk of AD at any age, 
and provides a continuous measure of increased risk of AD with increasing score and younger 
age of onset [16].  
 
Novel and Better Design of Trials 
There is a compelling need to more readily and efficiently test available and emerging candidate 
interventions, within a rigorous clinical trial framework, in order to secure a strong scientific 
evidence base upon which to advance development of potentially beneficial treatments for those 
at increased risk of dementia. Current trial approaches vary within and across countries, use 
disparate inclusion criteria and outcome measures, and lack interoperability. This limits the 
potential for head to head comparisons of effect sizes and limits the acquisition of converging 
evidence. A vital issue to address is improving approaches to risk stratification to enrich 
prevention clinical trials and allow for the most efficient use of resources for such trials in 
determining sample sizes and effect sizes. 
 
Open platform trials (OPT), which include Master Protocols that have key shared design 
components, common inclusion and exclusion criteria, and common outcome measures, 
provide a novel and attractive approach to the conduct of randomized controlled trials (RCTs), 
with potential application to dementia prevention [17]. Rather than relying on a traditional trial 
design with a single hypothesis to test a single intervention within a homogeneous group of 
patients, platform trials have the ability to test multiple interventions within the same indication, 
to select and adaptively randomize participants to those treatment arms with the highest 
probability of success, and to reduce opportunity cost through futility analyses which allow the 
early discontinuation of interventions that are unlikely to be successful [18]. Recruiting and 
engaging a pre-randomized Platform Trial Cohort (PTC) of individuals at increased risk of 
dementia shifts the recruitment paradigm away from its current model which is resulting in 
severe challenges and trial slowdown [19]. Furthermore, the pre-randomized data obtained from 

 
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the PTC can serve to help validate the inclusion criteria, study design, and development of the 
Master Trial Protocol (MTP) of the OPT. 
1.2 
Rationale 
There currently exists no medication or combination of medications to halt, reverse, or delay 
AD, or any other related neurodegenerative dementias. The necessary elements are now 
available, however, to make dramatic headway in dementia prevention. To address this, the 
CAN-THUMBS UP (CTU) study is a comprehensive and innovative program aimed to enroll and 
retain a Platform Trial Cohort (PTC) of individuals at risk of dementia, develop an interactive, 
and compelling online educational intervention, and to support an open platform trial with which 
to test a variety of multidomain interventions that might further benefit individuals at risk of 
dementia. Large-scale prevention studies require the sustained engagement of thousands of 
individuals willing to dedicate their time and effort into a program they believe will improve their 
lives. Therefore, during the initial phase of the CTU program, a community enrolled PTC of 
individuals who are cognitively unimpaired or have mild cognitive impairment (MCI) and with 
increased risk of dementia related to lifestyle risk factors will be recruited. The PTC will be 
engaged in a 45-week educational online Brain Health Support Program (BHSP) intervention, 
called Brain Health PRO (BHPro), aimed to increase dementia literacy, engagement, and 
convey best available evidence for lifestyle changes that can mitigate dementia risk.  
 
Compliance and evidence of BHPro’s impact, will be comprehensively evaluated and if 
successful, could culminate in a program disseminated for public use. The outcome data 
acquired from BHPro, will serve in the development of a separate Master Trial Protocol (MTP; 
Phase B). The MTP will create the framework for an open platform trial design, where 
participants from the PTC who have participated in BHPro will be evaluated for eligibility to 
enroll in RCTs testing multidomain lifestyle interventions. 
 
Through BHPro, individuals will be engaged in an innovative, accessible and multimodal 
platform conveying evidence-based information and guidance on lifestyle risk factors including, 
vascular, dietary, sleep, physical activity, cognition and social engagement. Furthermore, this 
study will employ mobile technology to more readily evaluate compliance and effects of lifestyle 
interventions, through the incorporation of wearable devices that track changes in activity levels 
and sleep patterns, and through app-based remote testing of cognitive function using paradigms 
of ‘burst’ cognitive testing and/or self-administered online cognitive testing. We expect these 
remotely acquired data will establish user acceptance and compliance with these methods. 
These results could be stage-setting for conducting more of the CTU’s evaluations remotely and 
with less disruption to participants, saving clinic visits and lowering trial costs that would in turn 
enable more interventions to be evaluated. Virtual clinical trials that might be performed 
completely remotely would allow research progress towards the dementia prevention goal 
during challenges such as COVID-19. Implementation of a fully remote online research protocol 
will provide an accessible approach to research, reaching a broader geography with recruitment 
of participants across Canada, which will help us to enroll more potential participants who can 
more easily join the program.   
 
Furthermore, identifying those with a declining cognitive trajectory during this phase of CTU 
would support precision-based trials to be undertaken with greater power and smaller sample 
sizes. Engaging the PTC in the BHPro intervention will provide an unprecedented opportunity to 
determine personalized profiles in this population, by collecting data on multiple variables such 
as sleep, diet, and social and physical activities, and obtaining cognitive slope data for up to 12 

 
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months. Thereafter we can tailor the specific intervention and study population for those that 
have a personalized profile of interest. 
2.0 
STUDY DESIGN 
This initial phase (Phase A) of CTU will be a prospective 12-month multi-center longitudinal 
intervention study to evaluate a web-based educational BHSP, called BHPro, focused on 
dementia literacy, self-efficacy, and modifiable lifestyle risk factors. Participants will be 
individuals who are either cognitively unimpaired or have MCI with increased risk related to 
lifestyle risk factors. At the conclusion of the BHSP intervention, participants will continue in the 
PTC with the opportunity to consent and enroll in further multidomain intervention trials. 
3.0 
STUDY GOAL AND AIMS 
3.1 
Overall Goal 
 
To develop and evaluate a 45-week web-based Brain Health Support Program (BHSP) 
intervention, called Brain Health PRO (BHPro), focused on dementia literacy, self-efficacy and 
modifiable lifestyle risk factors. Participants will subsequently be part of a PTC and may be 
evaluated for eligibility to participate in interventional dementia prevention trials under separate 
protocols. 
3.2 
Aims 
 
A. Our primary aim is to evaluate within-person change in dementia literacy following 
participation in BHPro. 
 
B. To evaluate within-person change following participation in BHPro, including change 
in: 
 
i. 
Self-efficacy and attitudes towards dementia and its screening  
ii. 
Individuals’ modifiable risk factors 
iii. 
Cognition 
iv. 
Physical activity and sleep quality as measured by actigraphy and EEG 
wearable devices 
 
C. To evaluate BHPro in relationship to: 
 
i. 
Levels of engagement (i.e., number of chapters completed), thresholds of 
compliance, ratings of satisfaction, and dropout rates from the intervention 
ii. 
Levels of engagement in the program as a function of individual characteristics 
and risk profile  
iii. 
Levels of engagement as a moderator of within person change in outcomes. 
iv. 
Association between change in modifiable risk factors and change in cognition. 
 
D. To develop a successful comprehensive national recruitment plan to fully enroll the 
PTC with engagement stakeholder groups including participants, citizen advisors, 
and community partners 

 
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4.0 
OUTCOME MEASURES 
 
4.1 
Primary Outcome Measure:  
 
A. The primary outcome will be change in dementia literacy following participation in the 
study, as measured by the Alzheimer’s Disease Knowledge Scale.  
4.2 
Secondary Outcome Measures: 
 
A. Change in self-efficacy following participation in the study, as measured by the 
General Self-Efficacy Scale (GSE). 
 
B. To evaluate BHPro, as measured by: 
 
i. 
Engagement using the online program (e.g., percentage of chapters 
completed) 
 
ii. 
User satisfaction ratings and evaluation of usability and acceptance (System 
Usability Scale and Technology Acceptance Model Questionnaire) 
4.3 
Exploratory Outcome Measures: 
 
A. Change in attitudes toward dementia following participation in the study as 
measured by Sections B and D of the Perceptions Regarding Investigational 
Screening for Memory in Primary Care (PRISM-PC).  
 
B. Change in modifiable risk factors following participation in the study, as measured 
by BHPro Lifestyle Risk Questionnaires.  
 
C. Cognition 
 
i. 
Change in global cognition based on a composite score using the 
Neuropsychological Test Battery (calculated as average Z scores standardized 
to the baseline mean and standard deviation). 
 
ii. 
Change in the subdomains of memory, processing speed, and executive 
functions based on composite scores derived from the Neuropsychological 
Test Battery (calculated as average Z scores standardized to the baseline 
mean and standard deviation). 
 
iii. 
Change in performance based on Burst Cognitive Testing that addresses:  
o Within-person change in asymptote, daily variation and within-burst 
practice effects of “burst” cognitive testing 
o Between- and within-person factors including self-rated emotional 
reactivity and its association with variation in cognitive performance over 
the BHPro intervention 
 

 
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iv. 
Change in performance based on online self-administered cognitive testing 
with the Cogniciti Brain Health Assessment 
 
v. 
Change in modifiable risk factors and relationship to change in cognition 
 
D. National recruitment success will be measured by:   
 
i. 
Enrollment rates per month and year across regions with centralized and                                   
local recruitment strategies 
 
ii. 
Screen fail rate and reasons 
 
iii. 
Projected enrollment rates vs actual enrollment rates 
 
E. Change in levels of physical activity and sleep quality, as measured by actigraphy 
and EEG wearable devices. 
 
F. Saliva sample collection, to characterize the distribution of age adjusted polygenic 
hazard scores within the BHSP study group. 
 
5.0 
ETHICS AND REGULATORY CONSIDERATIONS 
5.1 
Good Clinical Practice 
The current study will be conducted in compliance with the protocol, International Conference 
on Harmonization Good Clinical Practice (ICH-GCP) and the applicable regulatory 
requirements.  
Study personnel involved in conducting this study will be qualified by education, training and 
experience to perform their respective task(s) in accordance with GCP. 
5.2 
Institutional Review Board (IRB) / Research Ethics Board (REB) 
All relevant documents for this study will be submitted to an appropriate Institutional Review 
Board (IRB) or Research Ethics Board (REB) for review. A signed and dated letter documenting 
IRB/REB approval must be obtained prior to entering participants at the site. IRBs and REBs 
must be constituted and their authority delegated through the institution's normal process of 
governance according to applicable regulatory requirements for each participating site. Each 
participating institution must provide for the review and approval of this protocol and the 
associated informed consent documents and relevant participant materials by an appropriate 
IRB/REB. For each participating site, the protocol and associated informed consent and 
relevant participant materials will be submitted for approval to the designated IRB/REB, as per 
site local regulatory policies and procedures. The study will not commence at any site until initial 
approval is obtained from the designated IRB/REB and an approval to enroll notification is 
released to the site by the CTU central coordinating team. 
The investigator must obtain approval from the IRB/REB for all protocol amendments and, 
when warranted, changes to the informed consent document and/or participant materials. 
Protocol and informed consent form amendments can be made only with the prior approval 
from the CTU central coordinating team. The investigator may not implement any protocol 
deviation except where necessary to eliminate an immediate hazard to study participants, or 

 
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when change(s) involve only logistical or administrative aspects of the trial, i.e., change of 
monitor(s) or telephone number(s) (ICH 4.5.2). The investigator shall notify the IRB/REB of 
deviations from the protocol or serious adverse events occurring at the site, in accordance with 
local policy. 
5.3 
Electronic Informed Consent Process 
For the purposes of this study, the consent process will be completed remotely through the 
electronic Informed Consent Process (e-Consent).  
5.3.1 E-Consent Process 
A site team member will schedule a phone or video call with the participant where they will walk 
through the key elements of consent with the participant and allow time for questions before 
sending them the e-mail link to complete the e-Consent online. Each participant will be sent a 
unique URL link by e-mail to access the consent form electronically. The electronic consent 
process will include a user-friendly screen, in which participants can access each section of the 
consent through a series of virtual “doors” presented on the screen. Participants must 
successfully complete the consent process by going through each section and correctly 
answering 1-2 quiz questions per section to assess comprehension. Participants will be required 
to open and review the full pdf version of the Informed Consent Form (ICF) prior to providing 
consent, which will be available to download and save to a personal computer for the 
participants’ own records. Participants will then be presented with a statement of consent 
followed by two options in the form of radio buttons: “I agree” and “I disagree”. The participant 
will choose one of these options to activate a submit button. The database will store the date 
and time of page submission as a record of consent.  Participants will also be able to log back 
into the e-Consent platform at any time throughout the study to review the e-Consent 
information and to see a record of their consent. A hard copy of the ICF may also be mailed/e-
mailed to the participant by site staff if the participant prefers/requests it.  
 
For any participating sites whose designated IRB/REB requires a wet signature, a hard copy of 
the ICF may be mailed/e-mailed to the participant by site staff. Participants will sign the ICF and 
return a signed copy to the study site by e-mail or mail, according to site policy and/or 
participant preference. A copy of the final signed ICF with both participant and site study team 
signature will also be provided back to the participant once complete.  
 
If a study partner is available, they will also participate in the consenting process and be 
informed of their role and responsibilities in the study. They may also be asked to complete a 
study partner e-consent or sign and return a study partner ICF according to site policy and all 
applicable regulatory requirements. The method of obtaining and documenting the informed 
consent and the contents of the consent must comply with ICH-GCP and all applicable 
regulatory requirement(s).  
 
It will be made clear to each potential participant, and study partner (if applicable), that informed 
consent may be withdrawn at any time without needing to give a reason and that such 
withdrawal will not compromise the relationship between the participant and the Investigator nor 
the participant’s future treatment. 
 
The ICF must be in a language fully comprehensible to the prospective participants and ample 
opportunity must be given to inquire about the details of the study.  
 

 
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The ICF will include consent to access stored data for future analyses. Consent forms will 
specify that saliva samples are for research purposes only; the tests on the saliva samples are 
not diagnostic in nature and participants will not receive results. 
5.4 
Participant Confidentiality  
 
The Longitudinal Online Research and Imaging System (LORIS) [20] will house the data from 
participating institutions. LORIS is a web-based database solution for neuroimaging and other 
research data that is physically located at McGill University in Montreal. It will store data that 
has been processed to remove any direct identifiers of an individual study participant. Study 
subjects will be assigned a unique coded study identification number (LORIS Project Study 
Center ID (PSCID)) at the time of study enrollment that will be used to store their data.  
 
Local study sites will be responsible for storing all participant identifying information (name, 
contact, e-mail addresses) in secured encrypted databases and to maintain the master file that 
links the participant to their unique LORIS PSCID.  
 
Participant data collected by external sources including BHPro, Cogniciti Brain Health 
Assessment, MyCogHealth app, actigraphy device and the EEG Muse app will be de-identified 
and linked to the LORIS PSCID prior to being merged with the CTU dataset. Please also see 
section 13.0 Recording and Data Collection and Appendix 5 (CTU Flow of Data Figures) for 
additional information on temporary storage locations and secure transfer of various data 
sources into LORIS. 
 
The investigator will grant monitor(s) and auditor(s) from the Canadian Consortium for 
Neurodegeneration in Aging (CCNA) and regulatory health authorities’ access to the 
participant’s original medical records for verification of the data gathered and to audit the data 
collection process. The participant’s confidentiality will be maintained. Information about study 
participants will be made publicly available to the extent permitted by the applicable laws and 
regulations. In publications, only group data will be reported.  
 
In cases where participant identification is required (e.g. when an incidental finding is uncovered 
on coded data), the recruiting site study investigator for the participant will be given access to 
only the minimum identifying information required to link the participant to the incidental finding 
and move it towards a resolution. 
5.5 
Potential Risks and Benefits Associated with this Study 
 
5.5.1 Potential Risks 
Risks associated with study participation are minimal and include risks related to the process of 
undergoing neuropsychological and remote cognitive testing, which may lead to fatigue and/or 
frustration associated with participating in cognitively demanding testing. Questionnaires on 
mood and lifestyle risk may increase negative affect. There may be minimal discomfort or 
disruption of sleep with the application and removal of the actigraph device and EEG headband. 
There may be risks associated with a breach in confidentiality. Strict privacy and confidentiality 
procedures have been implemented (see section 5.4 Participant Confidentiality) to minimize this 
risk to the extent possible.  

 
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5.5.2 Potential Benefits 
Participants in this study may experience benefits from participating in a web-based educational 
program including increased knowledge and engagement regarding ways to promote their brain 
health, and possible positive reduction in their risk profiles, though such improvement cannot 
be predicted with any certainty. This study is expected to benefit the general community in 
the future by promoting public interest, literacy, and engagement in lifestyle interventions for 
brain health and dementia prevention through dissemination of BHPro to the broader public. 
6.0 
RECRUITMENT 
A centralized recruitment and site management approach will be utilized. There will be up to 7 
regional sites set up across Canada, all of whom will have full time, dedicated coordinators to 
receive participants. We will implement a nationwide recruitment campaign varying from 
geotargeted mailing to targeted social media and digital advertising with a goal to bring awareness 
of the study to more Canadians. Recruitment efforts using existing national and clinic registries 
and societies may also be utilized. Potential participants learning about the study through our 
advertising methods will be invited to visit a dedicated study website, available in both English 
and French, where they can express their interest about the study through a form that will help 
establish initial eligibility. The form will collect participant details such as name, age, preferred 
language, province of residence, first three letters/numbers from postal code, and contact 
information. Potential participants will be assigned to the site closest to them and each site will 
contact the potential participants that fall within their jurisdiction. Central recruitment will keep in 
close contact with the sites to adjust efforts as needed throughout the recruitment period. 
7.0 
PATIENT SELECTION 
7.1 
Inclusion Criteria  
Participants must meet all of the following inclusion criteria to be eligible for enrollment: 
 
1. Completion and documentation of the electronic Informed Consent Process (from the 
participant) 
2. Sufficient proficiency in English or French to undergo remote clinical and 
neuropsychological assessment and participate in an online educational program. 
3. Technical ability to participate in an online educational program and remote 
assessments (i.e. computer and internet access; ability to send and receive emails; 
ability to complete remote assessments) 
4. Sufficient vision and hearing to participate in online educational program and to undergo 
remote clinical and neuropsychological testing  
5. Ability to sit comfortably for a period of about 30 minutes 
6. Ages 60-85 
7. Meets criteria for No Dementia and meet criteria (according to CCNA Criteria, Appendix 
1) of one of the following: 
• 
Cognitively Unimpaired (CU)   
• 
Cognitively Unimpaired plus Subjective Cognitive Impairment (CU + SCI)   
• 
Mild Cognitive Impairment (MCI)  
8. AND Classified as being at increased risk of dementia based on at least one of the 
following:  
• 
First-degree family history of dementia 

 
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• 
Self-Reported or documented current and/or history at midlife (45-60 years) on any 
of the following lifestyle risk factors: 
 Hypertension (documented Systolic Blood Pressure > 140 mm Hg; OR physician 
diagnosis of hypertension; OR treatment for hypertension; OR other approaches 
to treatment (e.g. diet, exercise)) 
 Hypercholesterolemia (documented total cholesterol > 6.5 mmol/L; OR physician 
diagnosis of hypercholesterolemia; OR treatment for hypercholesterolemia; OR 
other approaches to treatment (e.g. diet, exercise) 
 Body Mass Index > 30 kg/m2 (derived from NIH Metric BMI Calculator) 
 Physical Inactivity (active is defined as engaging in a minimum of 20- 30 min of 
physical activity causing sweating and breathlessness, at least 2 times a week) 
9. Participant has a family physician or other healthcare provider and agrees to have the 
provider notified of participation in the study and incidental or other findings that may be 
clinically significant 
7.2 
Exclusion Criteria 
1. Participants who, in the opinion of the investigator, are not able to complete trial 
procedures remotely or adhere to the schedule of study assessments will be excluded 
from study participation. 
2. Individuals where English or French is not sufficiently proficient for remote clinical 
assessment, neuropsychological testing and participation in an online educational 
program.  
3. Participants who do not have sufficient vision and hearing for remote clinical 
assessment, neuropsychological testing participation in an online educational program 
4. Individuals who do not have the technical ability to participate in an online educational 
program. Technical ability is defined as having computer and internet access; ability to 
send and receive emails; ability to participate in remote assessments 
5. Individuals who have a clinical diagnosis of Dementia 
6. Clinical Dementia Rating (CDR; telephone/video-conference administration) Score of >1 
7. Total Score on the Montreal Cognitive Assessment (MoCA; video-conference 
administration) <13 
 
8.0 
STUDY PROCEDURES 
8.1 
Study Visits 
The schedule of study visits and procedures to be performed at each visit are outlined below 
and summarized in the Schedule of Events table (Appendix 2). A detailed description of 
study procedures is located in section 9.0. and a detailed description of study instruments is 
located in section 10.0. 
 
8.1.1 Technology for Remote Study Visits 
Screening and Baseline visits should be conducted using video-conference technology. Follow-
up study calls (Month 3, Month 6, and Month 9) can be completed by telephone. All remote 
study procedures administered over video-conference must be conducted on a secure platform 
(e.g. Zoom) that is compliant with Canadian Data Protection regulations, including the Personal 
Information Protection and Electronic Documents Act (PIPEDA). If a participant experiences 
technological difficulty (e.g. disruption in internet access) during a remote visit, any remaining 

 
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study procedures may be completed by telephone to the extent possible. Attempts should be 
made to re-schedule the video-conference visit to complete any measures that can only be 
completed by video within the allowed time frame prior to the next visit. Neuropsychological test 
battery administration at Screening, Baseline, and Month 12 conducted by video-conference 
technology will be recorded to assist with rater scoring, to ensure standard administration and 
scoring, and to help inform the study on feasibility of remote administration of the study 
assessments. 
 
8.1.2 Video Conference Screening (within 21 days prior to baseline) 
Participants who the Investigator considers to be appropriate for the study will complete the e-
consent process according to the process described in section 5.3 Electronic Informed Consent 
Process. Prior to the participant completing informed consent, the Investigator or his/her 
designee will schedule a phone or video call with the participant to explain the details of this 
study and allow participants sufficient time to study this information and the opportunity to ask 
any questions they wish, prior to continuing with the screening procedures.  
 
Informed consent must be obtained before any study-related activities are conducted.  
8.1.2.1 Study Partner (Optional) 
If the participant has a study partner available, he/she will be invited to participate in the study, 
be involved in the consenting process, and complete a Study Partner ICF. However, not having 
a study partner/informant available does not exclude the participant from joining this study. The 
role of the study partner will be to answer questions about the participant and his/her health, 
memory, daily functioning and behavior. If available, the study partner will provide input on 
completion of the following assessments: 
• 
Clinical Dementia Rating (CDR) at Screening 
• 
Mild Behavioral Impairment Checklist (MBI-C) at Baseline 
 
8.1.2.2 Video-Conference Screening Procedures 
 
The following procedures will be conducted remotely via secure video-conference technology 
during the screening period (Estimated Time to Complete: 3.0-3.5 hours). Screening procedures 
may be completed over multiple days as long as all procedures are completed within 21 days 
prior to the first scheduled baseline video-call visit. Procedures and instruments will be adapted 
for remote administration (see section 9.0 Study Procedure Descriptions and section 10.0 
Study-Specific Instruments). 
: 
• 
Review of inclusion/exclusion criteria 
• 
Consent for medical record review 
• 
Documentation of demographics, medical history (including past medical procedures), 
medications 
• 
Hearing and Vision assessment 
• 
CAIDE Score (derived score based on self-report and/or medical record review) 

 
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• 
Clinical Dementia Rating (CDR; if a study partner is not available, the CDR score will be 
decided by site-level research team consensus based on all other available information 
and utilizing best clinical judgement.) 
• 
Logical Memory 1 & 2 from Wechsler memory scale  
• 
Montreal Cognitive Assessment (MoCA) 
• 
Lawton Brody Instrumental Activities of Daily Living (IADL) 
• 
Brief Remote Neurological Exam (completed by Site Principal Investigator or qualified 
medical professional) 
 
8.1.2.3 Confirmation of Study Eligibility by Site Principal Investigator (or designated Co-
Investigator) 
Following completion of the screening assessments above, the Site Principal Investigator (or 
Co-Investigator) will be responsible for confirming participant diagnosis and eligibility to be 
enrolled in the study.  
 
8.1.3 Remote Baseline Visit (+/- 2 weeks) 
8.1.3.1 Video-Conference Baseline Procedures 
Participants who are enrolled in the study will complete the following baseline procedures 
remotely via video-conference with a member of the study team. (Estimated Time to Complete: 
2.5-3.0 hours) 
 
Participants may complete screening and baseline assessments at the same remote visit as long 
as the participant (and study partner if applicable) have provided consent prior to initiating any 
study-specific procedure and the site Study Investigator has confirmed study eligibility. Baseline 
procedures may also be completed over multiple days as long as all procedures are completed 
within 14 days of the first baseline video-call visit.  
 
• 
Neuropsychological Test Battery (adapted for remote administration; see section 10.1.4 
for test descriptions and information on remote administration; estimated time to complete 
is 1.0-1.5 hours)  
 
Craft Story 21 Immediate and Delayed Recall 
 
ADAS-Cog word recall, delayed recall, orientation 
 
Brief Visuospatial Memory Test-Revised (BVMT-R) 
 
Delis-Kaplan Executive Function System (DKEFS) Verbal Fluency 
 
Oral Trail Making Test A and B 
 
DKEFS Color-Word Interference Test 
 
Oral Symbol Digit Substitution Test 
 
Boston Naming Test (BNT) 15-Item 
 
“Burst” Cognitive Testing (training session) 
 
• 
Self-report height and weight 
• 
Body Mass Index (BMI) calculation (based on self-report current height and weight) 
• 
Saliva sample collection for genomics testing (Polygenic Hazard Score; with at-home 
collection kit) 
• 
Instructions on how to complete “Burst” Cognitive Testing and completion of training 
testing session  

 
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• 
Instructions on how to complete the Cogniciti Brain Health Assessment 
• 
Instructions and application of wearables for actigraphy and EEG recordings (see section 
9.3) 
• 
Instructions on how to register and participate in BHPro (see section 8.3) 
 
8.1.3.2 Baseline Functional and Behavioral Assessments 
Participants will receive a unique URL link by e-mail to complete the following functional and 
behavioral assessments electronically through the LORIS survey tool. Site study staff may also 
be available by phone/video-call to assist participants in completion of these questionnaires if 
preferred. Paper versions of the questionnaires may also be sent to participants by mail to 
complete at home and return to the site if preferred or requested by the participant. (Total 
estimated time: 30 minutes): 
• 
Geriatric Depression Scale (GDS) 
• 
Generalized Anxiety Disorder 7-Item Scale (GAD-7) 
• 
Sleep Disorders Questionnaire 
• 
COVID-19 Impact Survey 
• 
Research Satisfaction Survey 
 
The following questionnaire will be completed by study partner (if available).  
• 
Mild Behavioral Impairment Checklist (MBI-C) (estimated time: 10-15 minutes) 
 
8.1.4 Additional Remote Baseline Testing  
Following completion of the baseline procedures above, participants will also complete the 
following assessments remotely within approximately 2 weeks: 
• 
BHPro registration and completion of lifestyle risk questionnaires and goal setting 
(estimated time to complete is 1.0 hour; see section 8.3) 
• 
Weekly participation in BHPro (approximately 40 minutes/week)  
• 
“Burst” Cognitive Testing (5-10 minutes/day for 6 consecutive days following initial testing 
at Baseline Visit) 
• 
Cogniciti Brain Health Assessment (estimated time to complete is 20 minutes) 
• 
Actigraphy recording (continuous recording for 14 consecutive days) 
• 
EEG recording (nightly recordings for 3 consecutive nights) 
 
8.1.5 Month 3 Remote Follow-Up and Testing  
 
Participants will receive a follow-up phone call from a site study team member at approximately 
month 3 following baseline to assess continued interest in BHPro participation and satisfaction 
with BHPro.  
 
Participants will also receive notifications to complete the following activities remotely at month 3: 
• 
Notification via the MyCogHealth app will be sent to participant to complete “Burst” 
Cognitive Testing (estimated time: 5-10 minutes/day for 7 consecutive days)  
• 
Lifestyle risk questionnaires and goal setting within BHPro (estimated time: 20-30 
minutes; see section 8.3) 
 

 
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8.1.6 Month 6 Remote Follow-Up and Testing 
Participants will receive a follow-up phone call from a site study team member at approximately 
month 6 following baseline to assess continued interest in BHPro participation, and review any 
medical, lifestyle and diagnostic changes that have occurred since the baseline visit. The phone 
call will take an estimated 0.5-1.0 hours to complete. 
 
Participants will also complete the following cognitive assessments remotely: 
• 
Notification via the MyCogHealth app will be sent to participant to complete “Burst” 
Cognitive Testing (estimated time: 5-10 minutes/day for 7 consecutive days) 
• 
Study coordinator will send participant an email that contains a personalized link to 
complete the Cogniciti Brain Health Assessment (estimated time: 20 minutes) 
• 
BHPro outcome assessments (program usability and acceptability, dementia literacy, self-
efficacy, attitudes toward dementia; see section 8.3). These will be completed online within  
BHPro (estimated time: 30-45 minutes)    
• 
Lifestyle risk questionnaires and goal setting within BHPro (estimated time: 20-30 minutes) 
 
8.1.7 Month 9 Remote Follow-Up and Testing  
Participants will receive a follow-up phone call from a site study team member at approximately 
month 9 following baseline to assess continued interest in participation and satisfaction with 
BHPro. 
 
Participants will also receive notifications to complete the following activities remotely at month 9: 
• 
Notification via the MyCogHealth app will be sent to participant to complete “Burst” 
Cognitive Testing (estimated time: 5-10 minutes/day for 7 consecutive days)  
• 
Lifestyle risk questionnaires and goal setting within BHPro (estimated time: 20-30 minutes) 
8.1.8 Month 12 Remote Visit  
Participants will complete the following procedures remotely via video-conference with a 
member of the study team at approximately Month 12 for a remote re-assessment.  
 
Study participants will undergo the following procedures (Estimated Time to Complete: 4.0-5.0 
hours): 
• 
Documentation of changes to medical history (including medication changes and any 
medical procedures) that have occurred since the time of the last assessment 
• 
Self-report weight 
• 
Body Mass Index (BMI) calculation (based on self-report current height and weight) 
• 
Brief Remote Neurological Exam (completed by Site Principal Investigator or qualified 
medical professional) 
• 
Lawton Brody IADL 
• 
MoCA 
• 
CDR (if a study partner is not available, the CDR score will be decided by site-level 
research team consensus based on all other available information and utilizing best 
clinical judgement.) 
• 
Neuropsychological Test Battery (see section 10.1.4) 
• 
Instructions and application of wearables for actigraphy and EEG recordings (see section 
9.3) 

 
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8.1.8.1 Month 12 Functional and Behavioral Assessments 
Participants will receive a unique URL link by e-mail to complete the following functional and 
behavioral assessments electronically through the LORIS survey tool. Site study staff may also 
be available by phone/video-call to assist participants in completion of these questionnaires if 
preferred. Paper versions of the questionnaires may also be sent to participants by mail to 
complete at home and return to the site if preferred or requested by the participant. (Total 
estimated time: 30 minutes): 
• 
Geriatric Depression Scale (GDS) 
• 
Generalized Anxiety Disorder 7-Item Scale (GAD-7) 
• 
Sleep Disorders Questionnaire 
• 
COVID-19 Impact Survey 
• 
Research Satisfaction Survey 
 
The following questionnaire will be completed by study partner (if available).  
• 
Mild Behavioral Impairment Checklist (MBI-C) (estimated time: 10-15 minutes) 
 
8.1.8.2 Month 12 Remote Testing  
Participants will also complete the following assessments remotely within approximately 2 weeks: 
• 
“Burst” Cognitive Testing (estimated time: 5-10 minutes/day for 7 consecutive days) 
• 
Cogniciti Brain Health Assessment (estimated time: 20 minutes) 
• 
Actigraphy recording (continuous recording for 14 consecutive days) 
• 
EEG recording (nightly recordings for 3 consecutive nights) 
• 
BHPro outcome assessments (program usability and acceptability, dementia literacy, self-
efficacy, attitudes toward dementia). These will be completed online within BHPro 
(estimated time: 30-45 minutes)    
• 
Lifestyle risk questionnaires and goal setting within BHPro (estimated time: 20-30 minutes) 
 
 
8.1.9     End of Study Remote Visit (Early Discontinuation) 
 
Participants who have logged in and completed the registration process for BHPro but choose 
to withdraw and/or discontinue participation (see also: section 11.0 Early Discontinuation 
Procedures) in the BHPro Intervention for any reason will have the opportunity to complete  
further study visits per protocol up to the end of the study with their ongoing consent. Their 
continued participation should be encouraged to address the impact of early discontinuation 
compared to completion of the BHPro Intervention. If a participant declines to complete further 
study visits per protocol, an End of Study Remote Visit will be completed as close as possible to 
the time of study discontinuation. Ideally, the End of Study Remote visit will include all of the 
procedures and assessments described in the Month 12 Remote Visit (section 8.1.8). If the 
participant is not willing to complete all of the procedures and assessments, the  BHPro outcome 
assessments (program usability and acceptability, dementia literacy, self-efficacy, attitudes 
toward dementia) should be prioritized. These will be completed online within BHPro (estimated 
time: 30-45 minutes). An additional priority is completion of the  Lifestyle risk questionnaires and 
goal setting within BHPro (estimated time: 20-30 minutes). For further detail please refer to the 
Study Procedures Manual. 
 

 
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8.2  Platform Trial Cohort (PTC) 
All participants who meet CTU eligibility criteria (see sections 7.1 and 7.2) will be enrolled in the 
PTC and will participate in the BHSP study with monitoring of their engagement over the course 
of 12-months. Data collected during the BHSP study will be used to model the Open Platform 
Trial (OPT) to conduct future RCTs utilizing participants from the PTC (Phase B of CTU). Once 
participation in the BHSP study has ended, participants may be offered potential participation in 
future multidomain intervention RCTs of the CTU program under separate protocols. For 
participants who are interested and meet inclusion criteria for specific RCTs within the OPT, a 
separate informed consent will be signed prior to participation. 
 
8.3  Brain Health Pro (BHPro) Intervention 
The BHPro Intervention is a 45-week, multidomain, web-based formal educational program 
designed to increase dementia literacy, foster engagement, and convey best available evidence 
for lifestyle changes that can mitigate dementia risk. The program was developed as a 
collaborative effort by CCNA investigators with recognized expertise in the program’s content 
areas, along with input from older-adult citizen advisors. The program was refined and updated 
based on feedback from focus-groups and a 3-month pilot study to assess usability and 
accessibility.  
 
Participants will receive instructions on how to register and participate in the program at the 
remote baseline study visit.  
 
8.3.1 Program Content 
Participants will register on the BHPro website and obtain a personal password. Participants will 
need to provide a valid e-mail address and password in order to login and participate in BHPro. 
Participants will also be asked to enter a preferred name (this can be a first name or nickname), 
which they will be referred to as throughout their participation in the program. Name and e-mail 
address will not be included in the study data set. All data from BHPro will be de-identified and 
linked to the LORIS PSCID prior to being included in the CTU database. Registration will also 
include viewing a brief video explaining the program, demographic questions and lifestyle 
questionnaires including general questions related to socio-demographic profile, health, and 
lifestyle.  
 
BHPro is organized into the following 8 content modules: 
 
 
1 
Motivation, self-efficacy, positive health, 
dementia, environment vs genetic risk, cognitive 
aging and healthy lifestyle, medication 
2 
Physical activity 
3 
Cognitive engagement  
4 
Diet 
5 
Sleep 
6 
Social and Psychological Health 
7 
Vascular health  
8 
Vision and hearing 
 

 
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The program content is provided progressively to deliver new weekly content (i.e. module 
chapters) of approximately 40 minutes. Participants will have access to new content on 4 
modules each week (10 minutes/module; alternating every 2 weeks) through an email push 
notification, as an approach to maintain interest. Participants will be invited to visit the web site 
at their own rate but encouraged to spend a minimum of 40 minutes/week on the program. 
 
Information is organized as chapters within the modules, which contain scientific evidence, 
explanation of principles and mechanisms that underlie positive effects, specific 
recommendations (e.g., type and dose of prescribed physical exercises), suggestions to 
improve behavior in everyday life and typical barriers and tips to circumvent them. Content 
format will include visual and auditory text, pictures, animations, quizzes, questionnaires and 
interactive exercises. 
 
8.3.2 Personalized Profiles on Modifiable Lifestyle Risk Factors 
Participants will be asked to complete brief online lifestyle risk questionnaires approximately 
every 3 months (see Appendix 3 for descriptions of the BHPro Lifestyle Risk Questionnaires). 
Questions will be related to the content in the program modules (e.g. sleep, diet, physical 
activity, cognitive engagement, social and psychological health, sensory). A personalized profile 
will be developed for each participant based on their responses to the lifestyle questionnaires. 
Participants will also be asked to set goals based on their risk profile and to re-visit and update 
their goals every three months.  Participants will be encouraged to focus on the content 
modules that are related to their risk profile. Although participants will have access to all content 
modules within the program, modules that are suggested to the participant based on their risk 
profile will be highlighted.  
 
8.3.3 BHPro Outcome Variables and Data Collection  
The following data and assessments will be collected directly through BHPro. For more detailed 
information on the specific instruments see section 10.0. (Study Specific Instruments): 
 
Outcome 
 
Measure/Data Collected 
Frequency 
Engagement using BHPro 
Direct monitoring of several 
parameters that could include: 
- Dates and time of program use 
- % completion of chapters at 
regular intervals 
- % completion of questionnaires 
- Other parameters may be added 
to this list as the studies goes on 
Weekly/monthly 
Acceptability (usefulness 
and ease of use) of BHPro 
Adapted version of the Technology 
Acceptance Model questionnaire 
Every 6 months 
Usability of the BHPro 
Adapted web-based version of the 
System Usability Scale (SUS) 
Every 6 months 
Dementia Literacy 
Alzheimer Disease Knowledge 
Scale (ADKS) 
Every 6 months 
Participant Self-Efficacy 
 
General Self-Efficacy Scale (GSE) 
Every 6 months 

 
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Outcome 
 
Measure/Data Collected 
Frequency 
Attitudes towards dementia 
and dementia screening 
Sections B and D from The 
Perceptions Regarding 
Investigational Screening for 
Memory in Primary Care (PRISM-
PC) Questionnaire 
Every 6 months 
 
9.0 STUDY PROCEDURE DESCRIPTIONS 
 
9.1.1 Sociodemographics  
Sociodemographic data (sex, gender identity, age, handedness, languages, marital/partner 
status, living circumstances, reproductive history, education, employment history) will be 
captured. 
 
9.1.2 Medical/Surgical/Family History  
Relevant medical and surgical history will be captured as well as relevant medical history of 
first-degree relatives. A list of current medications will also be documented.  
 
9.1.3 Hearing and Vision Assessment 
Hearing and vision will be assessed at baseline. Vision and hearing ability will be assessed by 
questions on perceived visual and auditory ability and an inventory of aids used. Participants 
must have relatively sufficient vision (with corrective lenses or other aids) so that they can 
identify symbols, stimuli and text presented on a computer screen in front of them. Participants 
must also have sufficient hearing (corrected with hearing aids or other voice amplification 
devices) to be able to follow spoken instructions and information that is presented only verbally. 
9.1.4 CAIDE Score 
The CAIDE Dementia Risk Score is a validated tool to predict late-life dementia risk (20 years 
later), based on midlife vascular risk factors [15]. Its components are age, education, sex, 
systolic blood pressure, body mass index, total cholesterol and physical activity. Participants will 
be asked about current vascular risk factors and history at mid-life (40-60 years old) to capture 
both a current and mid-life CAIDE Score.  Since this remote study does not include an actual 
measure of blood pressure nor is there a blood draw for total cholesterol, the rating of these 
components will be based either on medical record review (if available) or on participant self-
report (i.e. confirmation of physician diagnosis, medical treatment, other approaches to 
treatment). Physical activity is defined as engaging in a minimum of 20- 30 min of physical 
activity causing sweating and breathlessness, at least 2 times a week. BMI will be captured 
using the NIH BMI Metric Calculator 
(https://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmi-m.htm). 
 
9.1.5 Saliva Sample for Genomics Testing (Polygenic Hazard Score) 
A saliva sample collection kit (OG-500 kit, DNA Genotek, Kanata, Ontario) will be sent to each 
participant for extraction of DNA. Study staff at SRI will be responsible for mailing the kits to the 

 
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participant’s home. The at-home kit will include detailed instructions on how to collect the 
sample and a study team member will provide guidance to the participant on how to properly 
collect and ship the sample during the Baseline video-call visit. A total of 2 mls of saliva will be 
collected by passive drool in 1 tube. Participants will be instructed not to eat, drink, smoke, or 
chew gum for 30 minutes prior to giving the sample. The samples will be collected, handled, 
stored and shipped according to established standard operating procedures. Instructions for 
collection, handling and shipping of saliva samples for DNA testing will also be provided in the 
Study Procedures Manual.  
 
De-identified samples will be sent to the Clinical Genomics Centre in the Mount Sinai Hospital, 
600 University Ave, Toronto, ON M5G 1X5, Canada and will be processed under the guidance 
of Dr. Kathy Siminovitch. Samples will be stored for the duration of the study and until all 
planned analyses are complete, after which they will be properly destroyed according to 
established lab procedures.  
 
A Polygenic Hazard Score (PHS) will be derived from a planned panel of single nucleotide 
polymorphisms that describes age of onset and ADD risk [16] . Both raw and processed data 
will be posted to the LORIS server.   
 
9.1.6 Remote Neurological Exam 
A brief neurological examination will be conducted during screening by the site principal 
investigator or a designated medically qualified professional. The examination will be completed 
by a telemedicine visit using secure PIPEDA compliant video-conference technology (e.g. 
Zoom). The exam will be conducted following guidance from the American Academy of 
Neurology (AAN) and the Telemedicine and COVID-19 Implementation Guide 
(https://www.aan.com/siteassets/home-page/tools-and-resources/practicing-neurologist--
administrators/telemedicine-and-remote-care/20-telemedicine-and-covid19-v103.pdf) and will 
include assessment of mental status, language, calculations, memory, cranial nerves, gate, 
motor, sensory, and cerebellar function.  
9.2 
Online Cognitive Testing 
Participants will be asked to complete cognitive testing remotely throughout the duration of the 
study. Participants will be provided with detailed instructions on each remote assessment at the 
baseline video-conference with a study team member. The following online cognitive 
assessments will be completed (see Schedule of Events (Appendix 2) for timing of 
assessments): 
 
9.2.1 Cogniciti Brain Health Assessment 
The Cogniciti Brain Health Assessment (BHA) is a self-administered validated computerized 
cognitive assessment comprised of four tests (Spatial Working Memory, Stroop Interference, 
Face-Name Association, and Number-Letter Alternation). Total time to complete testing is 
approximately 20 minutes. Cogniciti technology allows for secure, remote, unsupervised 
assessment of participants using a web-based system and is compatible with any desktop and 
laptop device that has web browser capability and an internet connection. Participants will 
receive instructions from a study team member on how to complete testing at Baseline, Month 
6, and Month 12 (see section 10.1.5 for full description of cognitive measures included in the 
Cogniciti BHA).  

 
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9.2.2 MyCogHealth App “Burst” Cognitive Testing  
MyCogHealth is an iOS/Android app for self-administered cognitive assessments and 
customizable surveys of health behaviors, risk factors, and patient-reported outcomes. The 
MyCogHealth app currently supports iPhones from version 6 and up (running iOS 11 and up). 
The app also supports Android 6 and up. The software is built on Health Insurance Portability & 
Accountability Act (HIPAA)-compliant scheduling and data management server-side software 
that permits individually tailored assessment protocols and scheduling. The platform is user-
friendly and was developed for use with older adults. Based on available data pertaining to 
smartphone use and ownership in this age population, we anticipate that the majority of 
participants will have a personal smartphone that is compliant with this program. With 
assistance from a study team member, each participant will install the mobile application 
software on their personal mobile device. For individuals lacking a compliant smartphone, CTU 
will provide up to 150 participants with Android devices, including training. Participants will be 
oriented to the application software during the baseline remote video-conference, and will 
complete a training session on the mobile battery with the study team member present via 
video-conference to answer questions and trouble-shoot any issues that may arise. Ongoing 
technical support may also be provided to participants, over the duration of their participation in 
the 12-month BHSP, as needed through Dr. Scott Hofer’s CogTech Group at the University of 
Victoria. For the purposes of providing technical support, participant contact information (name, 
telephone number, email address) and study ID may be sent by encrypted email to study staff at 
the CogTech Group at the University of Victoria. 
 
“Burst” cognitive testing using the MyCogHealth app will consist of five measurement “bursts” 
over approximately 12 months, at Baseline, Month 3, 6, 9 and 12. Each measurement burst will 
involve two mobile assessment sessions per day for seven consecutive days, with sessions that 
take approximately 5-10 minutes to complete. Each session includes 3 cognitive tests, Symbol 
Match, Dot Memory, and Trail-Making A and B, as well as several brief questions assessing 
state factors at the time of testing (e.g., mood, fatigue, subjective impression of cognitive ability). 
See section 10.1.6 for full description of cognitive measures. 
9.3 
Physical Activity and Sleep Monitoring 
Participants will be asked to participate in at-home physical activity and sleep monitoring 
throughout the duration of this study through the application of Actigraphy and EEG headband 
devices. Participant contact information (name, telephone number, email address, mailing 
address) and study ID will be sent by encrypted email to study staff at Sunnybrook Research 
Institute (SRI, University of Toronto, Ontario), a participating CTU site. Devices will be centrally 
distributed from SRI to participants and detailed instructions on application and use of devices 
will be provided to participants along with guidance from an SRI study team member via video-
conference. For participants enrolled at French-speaking sites, a study team member from that 
site may assist SRI with participant communications. 
 
Participants may also be invited in a sub-study, based at SRI (Appendix 6), which will add 24-
hours of cardiopulmonary monitoring for sleep apnea and its physiological consequences using 
a pair of adhesive band-aid like sensors. The optional sub-study will be conducted under a 
separate study protocol with a separate consent form. 
 

 
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CTU will provide the Actigraphy devices, EEG headbands, and iPods to be used for the duration 
of this study, which should allow for all participants to participate in recordings at Baseline and 
Month 12. As described earlier, EEG recordings will be captured on the Muse app installed on 
the iPod. 
9.3.1 Actigraphy  
Physical activity and sleep monitoring using actigraphy (Axivity AX3) will be assessed at 
Baseline and Month 12. The Axivity is an accelerometer used to detect movement, vibrations, 
and orientation changes. The Axivity device will be mailed to participants. After study equipment 
and materials are shipped to and received by the participant, study staff will instruct the 
participant on the proper application and use of the Axivity over remote video-conference. The 
participant will be given an instruction card containing contact information of study staff should 
they have any questions. The participant will be shown how to place the device on their non-
dominant wrist by study staff, and participants will be instructed to wear the devices 
continuously for 14 days, even when bathing or swimming. During the 14 days, participants will 
be asked to track their work and sleep hours in a diary. At the end of 14 days, participants will 
return the device to SRI using a pre-paid, pre-addressed package. This procedure will be 
repeated at the Month 12 remote visit.  
9.3.2 EEG Recording 
Overnight EEG recording will be assessed at Baseline and Month 12 using the MUSE S 
Headband (Interaxon Inc, Toronto, Ontario, Canada). The MUSE S Headband is a 
commercially-available consumer headband that has 5 sensors, 2 on the forehead, 2 behind the 
ears, plus 1 reference sensors, to detect and measure EEG signals. The EEG headband and 
iPod with Muse app installed will be mailed to participants. After study equipment and materials 
are shipped to and received by the participant, study staff will instruct the participant on the 
proper application and use of the Muse over remote video-conference. Participants will use the 
iPod with the Muse app to capture EEG sleep recordings. Study coordinators will use a pseudo 
email and password, which will be linked to a central study e-mail address (provided by the 
sleep team at SRI) to initially sign-up for the app prior to mailing the study iPod to participants. 
Recordings will be linked to the associated Muse headband device number only and will not 
include any PHI. 
 
The participant will be given an instruction card containing contact information of study staff 
should they have any questions. On the night after the baseline visit, participants will wear the 
headband, start the recording using the provided iPod, and stop the recording the following 
morning. They will repeat this for an additional 2 nights (3 consecutive nights total), charging the 
devices in-between each recording according to the instructions provided, and then return the 
EEG headband, iPod, and the Axivity device described above, after 14 days of actigraphy. 
Participants will be provided with a pre-paid, pre-addressed package. Data is uploaded 
automatically from the iPod to a manufacturer-supported cloud server. Raw data will be 
downloaded from the cloud server, processed by the study team at SRI, and then will be 
uploaded to LORIS. This procedure will be repeated at the Month 12 visit. 
 
9.4 
Data Collection from other CCNA Studies 
A subset of CTU: BHSP participants may be recruited from those participating in other CCNA 
studies such as COMPASS-ND and SYNERGIC-2. If participants consent to have their data 

 
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from other CCNA studies shared with CTU: BHSP, the following data will be accessible (via 
LORIS) for use within BHSP:  
• 
Clinical Data 
• 
Neuropsychological Testing 
• 
Biospecimen 
10.0 
STUDY-SPECIFIC INSTRUMENTS 
10.1 
Cognitive Measures 
 
10.1.1 Clinical Dementia Rating (CDR) 
The CDR is a validated 5-point composite scale used in longitudinal AD research to 
characterize cognitive and global function performance applicable to AD and related dementias 
[21]. Information is obtained through a semi-structured interview of the patient and a reliable 
informant or collateral source (e.g. family member). The three cognitive domains include 
memory, orientation, and judgment/problem solving and the three functional domains include 
community affairs, home and hobbies and personal care. The five possible scores for each 
domain [0, 0.5, 1, 2, and 3] represent a range of impairment (e.g. score of 0 represents no 
impairment and a score of 3 represents severe impairment). If an informant is not available, the 
CDR score will be decided by site-level research team consensus based on all other available 
information and utilizing best clinical judgement. 
 
10.1.2 Logical Memory I and II 
Logical Memory I and II (Story A) from the Wechsler memory scale [22] will be completed during 
remote screening by tele/video-conference. The participant will be instructed to listen to a story 
and repeat it back after it has been read. They will then be asked to recall the story 
approximately 30 minutes later.  
 
10.1.3 Montreal Cognitive Assessment (MoCA) 
The MoCA is a 10-minute test that provides a global assessment of cognition, covering domains 
of memory, language, attention, visuospatial, and executive functioning [23]. An audiovisual 
version of the full MoCA has been validated for remote administration by video-conference[24]. 
Instructions for administration of full MoCA by video-conference can be found at 
https://www.mocatest.org/remote-moca-testing/. 
 
10.1.4 Neuropsychological Test Battery (NTB) 
The NTB will be administered remotely at baseline and Month 12 by video-conference. The 
sessions will be audio recorded to facilitate rater scoring and for quality control. Full details on 
rater training and the administration for remote testing will be provided in the Study Procedures 
Manual.    
 
Participants will receive all necessary testing materials by mail ahead of the testing session. The 
battery requires approximately 1.0-1.5 hours to administer.  
 

 
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Tests that have been administered clinically in the past 12 months will not be repeated (unless 
there is a discrepancy between test versions). Consent forms for each site will include a 
statement asking participants to allow for their clinical results from tests overlapping with the 
CTU battery to be entered into the CTU case report form. If a patient was assessed using a 
different version of the same test used in the CTU neuropsychological battery, the test will be 
repeated using the version consistent with the study. 
 
 
Domain 
Test 
Description 
Time 
(Mins) 
Memory & Orientation 
 
Craft Story 21 Immediate and 
Delayed Recall 
Story learning and 
Recall 
10-15 
ADAS-Cog Immediate & Delayed 
Word Recall  
 
Word List Learning and 
Recall 
10-15 
ADAS-Cog Orientation 
Orientation 
2-3 
Brief Visuospatial Memory Test - 
Revised 
 
Figure learning and 
Recall 
 
10-15 
Attention, Processing 
Speed  
 
Digit Symbol Modalities Test-
Oral Version  
Attention and 
Processing speed  
 
5 
Oral Trail Making Test (Part A) 
Visual and Motor 
Processing Speed 
2-3 
DKEFS Color-Word Interference 
Test- Color Naming & Word 
Reading 
Attention and 
Processing Speed 
5 
Executive Function  
 
DKEFS Verbal Fluency 
Phonemic (letter) 
fluency, Semantic 
(category) fluency, 
Category Switching  
2 
Oral Trail Making Test (Part B  
Switching attention  
 
3-5 
DKEFS Color-Word Interference 
Test- Inhibition  
Inhibition  
5-10 
Visuoperceptual & 
Construction 
 
Brief Visuospatial Memory Test-
Revised Copy 
 
Visuoconstruction  
 
3 
Speech & Language 
Boston Naming Test-15 Item 
Confrontational Naming 
5-10 
 
10.1.4.1 ADAS-Cog (Word Recall, Delayed Recall, Orientation) 
The ADAS-Cog administration will be restricted to the Word Recall and Orientation subtests, as 
these have demonstrated to have the greatest sensitivity to change in MCI [25]. For Word 
Recall, participants are given three trials to learn a list of 10 high-frequency, high imagery nouns 
presented one at a time in block letters on white cards. Immediate recall is assessed after each 
presentation trial. Delayed recall is assessed after approximately 5 minutes. Orientation for 
person, time and place is assessed with 10 examiner-administered questions.  

 
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10.1.4.2 Boston Naming Test (BNT) – 15-item 
This is an abbreviated version of the Boston Naming Test and will be administered to assess 
visual confrontation naming [26]. Participants are asked to identify (i.e., name) line drawings of 
objects. 
 
10.1.4.3 Brief Visuospatial Memory Test-Revised (BVMT-R) 
On this task, participants are presented with a 2 x 3 array of six line drawings for ten seconds. 
After the display is taken away, participants are asked to draw each figure accurately and in its 
correct location on the page. There are three learning trials, a 25-minute delayed recall trial, a 
delayed recognition memory trial and a copy trial [27]. 
 
10.1.4.4 Craft Story 21 Immediate and Delayed Recall 
This test assesses the ability to recall a story[28]. Participants are read a story and are 
immediately asked to recall what they can remember. After a 20-minute delay, participants are 
asked again to recall the story.  
 
10.1.4.5 Digit Symbol Modalities Test-Oral Version 
This is a timed task that gives participants 120 seconds to orally match geometric figures with 
specific numbers according to a defined key (specifying which symbols are assigned to which 
numbers) that is provided at the top of the stimulus page [29]. 
 
10.1.4.6 DKEFS Color-Word Interference Test (CWIT) 
This timed task requires participants to (1) name a series of colors, (2) read a series of words 
and then (3) name the color of the ink of dissonant color words (i.e., must say “green” when the 
word red is written in green ink) [30]. The latter task is a measure of response inhibition as 
participants must inhibit an overlearned verbal response of reading the particular word (red) in 
favor of generating a conflicting response of naming the different ink color (green). For the 
fourth trial, participants must alternate between naming the ink color of dissonant color words 
and simply reading the word and ignoring the ink color (inhibition and switching). The score is 
total time it takes to complete each trial. The maximum time for the color naming and word 
reading trials is 90 seconds and the maximum time for the inhibition and inhibition switching 
trials is 180 seconds. 
 
10.1.4.7 DKEFS Verbal Fluency 
This verbal fluency test includes phonemic (letter) fluency, semantic (category) fluency and 
category switching [30]. For the phonemic fluency task, the participant is asked to generate words 
that begin with a particular letter as quickly as possible, within a 60 second time period. Three 
trials are given, each with a different letter. The semantic fluency task asks participants to verbally 
generate as many words as they can according to specific categories (animals and boys names) 
with a 60 second time period. The category switching task asks participants to alternate between 
saying words from two different semantic categories (fruits and furniture) with a 60 second time 
period.  
 

 
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10.1.4.8 Oral Trail Making Test  
The oral version of the Trail Making Test provides an assessment of sequential set-shifting 
without the motor and visual demands of the written Trail Making Test [31]. For Part A, 
participants are asked to count from 1 to 25 as quickly as possible. For Part B, participants are 
asked to switch between number and letter in sequential order (e.g. 1-A, 2-B, 3-C) until the 
number 13 is reached. Scoring is the total time to complete each part.  
 
10.1.5 Cogniciti Brain Health Assessment 
The Cogniciti Brain Health Assessment (BHA) is a self-administered online assessment of 
memory and executive function, comprised of four cognitive tests [32]. The Cogniciti BHA also 
includes a demographic and health questionnaire. The four cognitive tests included in the 
Cogniciti BHA are: 
 
1) Spatial Working Memory is a test of visuospatial working memory. This task requires 
participants to match several pairs of hidden shapes across three trials and to avoid 
unnecessarily returning to previously searched locations. Number of responses across three 
trials is measured.  
2) Stroop Interference is a speeded test of response inhibition. Participants are required to 
identify the number of words shown on each trial. During interference trials, the number of 
words is incongruent with the meaning of the word (e.g. the word “two” is written one time). 
Median reaction time on incongruent trials is measured. 
3) Face-Name Association is a test of associative recognition. The participant is shown 
various faces paired with names and then completes a recognition task. Recognition 
accuracy is measured.  
4) Number-Letter Alternation is a test of alternating attention. Participants are required to 
alternate sequencing numbers and letters in ascending order as quickly as possible. Time to 
completion is measured.  
 
10.1.6 “Burst” Cognitive Testing 
Participants will undergo five intensive measurement bursts, spaced approximately three 
months apart, over 12 months (at Baseline, Months 3, 6, 9, and 12) using the MyCogHealth 
mobile application. Each measurement burst will involve two mobile assessments per day for 
seven consecutive days. Each assessment session will take approximately 5-10 minutes to 
complete, and will include the 3 cognitive tests included in the current MyCogHealth battery (i.e., 
Symbol Match, Dot Memory, and Trail-Making A and B), as well as several brief questions 
assessing state factors at the time of testing (e.g., mood, fatigue, subjective cognitive ability).  
Cognitive Tasks  
Each cognitive task in the mobile battery takes 1-2 minutes to complete, ensuring feasibility for 
use in intensive measurement studies that include multiple sessions within a day. 
Symbol Match assesses attention and information processing speed. Participants are shown a 
row of three symbol pairs at the top of the screen, and are simultaneously presented with two 
symbol pairs at the bottom of the screen. Stimuli are presented until a response is provided. The 
task is to decide, as quickly as possible, which of the two pairs presented at the bottom of the 
screen matches one of the pairs at the top of the screen. Participants complete 12 trials of this 
task. The dependent variable is median response time of correct trials. 

 
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Dot Memory assesses visual short-term memory. Each trial consists of 3 phases: Encoding, 
distraction, and retrieval. During the encoding phase, the participant is asked to remember the 
locations of 3 red dots on a 5 x 5 grid. After a 3-second study period, the grid is removed and 
the distraction phase begins, during which the participant is required to locate and touch all the 
F’s among an array of E’s. After performing the distraction task for 8 seconds, an empty 5 x 5 
grid re-appears on the screen, and participants are prompted to recall the locations of the 
initially presented 3 dots. Participants complete 4 trials of this task (encoding, distractor, 
retrieval), with a 1-second delay between trials. 
Digital Trail Making Test assesses complex attention/controlled sequential processing. It is a 
digital analogue of the classic neuropsychological task.  
Survey 
As part of each mobile assessment participants will be asked to complete a series of single-item 
questions that assess state factors that can affect cognition (e.g. mood, fatigue, physical 
activity, subjective cognitive ability). 
10.2 
Behavioral and Functional Measures 
Participants will complete the following behavioral and functional measures remotely through 
the LORIS survey tool. Each survey form is generated with a unique URL. This survey link URL 
can be emailed directly to respondents for survey completion from home. Participants will be 
provided with contact information for site study staff for any questions, concerns or if they 
experience any technical difficulties with completing the assessments.  
 
10.2.1 COVID-19 Impact Survey 
This is a 14-item questionnaire developed by the National Alzheimer’s Coordinating Center 
(NACC) to assess the impact that the COVID-19 pandemic has had on older adults. Questions 
include symptoms, testing, social isolation, loneliness and disruption to everyday life [33].  
 
10.2.2 Generalized Anxiety Disorder 7-Item Scale (GAD-7) 
Anxiety symptoms will be assessed with the GAD-7 [34]. The participant is asked how 
frequently they felt the way that is described in a given item over the last two weeks (choices 
are “Not at all sure”, “Several days”, “Over half the days” & “Nearly every day”). If any of the 
items are indicated to have been experienced several days or more, there is a follow-up 
question on how much difficulty this created in being able to work, take care of things at home, 
or get along with other people. The score is based on the frequency of each experienced item 
with “Not at all sure” =0 points, “Several days” =1 point, “Over half the days” =2 points, and 
“Nearly every day” =3 points. A score greater or equal to 10 suggests generalized anxiety. 
 
10.2.3 Geriatric Depression Scale (GDS) 
Depressive symptoms will be assessed with the 15-item Geriatric Depression Scale [35]. This is 
a 15-item scale of Yes/No questions where each point represents a depressive answer. A score 
over 10 suggests depression and a score over 15 suggests major depression. 
 
10.2.4 Lawton Brody Instrumental Activities of Daily Living (IADL) Scale  

 
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This is a 10-15-minute scale that can be completed by self-report or by informant (if available) 
and captures functional ability on 8 instrumental activities of daily living (telephone use, 
shopping, food preparation, housekeeping, laundry, transportation, medication management, 
and ability to handle finances) [36]. Each activity has a series of levels of capability described, 
ranging from full capability to no capability. A total score out of 23 is derived from the levels of 
capability for each activity with a higher score representing better functional capacity.  
 
10.2.5 Mild Behavioral Impairment Checklist (MBI-C) 
The MBI-C is a 32-item scale that assesses severity of behavioral symptoms in 5 domains: 
impaired drive/motivation (apathy); emotional dysregulation (mood/anxiety symptoms); impulse 
dyscontrol (agitation/aggression/abnormal reinforcement and reward salience); social 
inappropriateness (impaired social cognition); and abnormal thoughts/perception (psychotic 
symptoms) [37]. The MBI-C will be completed by a study partner/informant (if available). The 
study partner will be asked to select “Yes” only to each behavior that has been present for at 
least 6 months and is a change from the participant’s longstanding behavior.  
 
10.2.6 Research Satisfaction Survey 
A brief Research Satisfaction Survey will be administered to the participant at Baseline, Month 6 
and Month 12 to evaluate satisfaction with this study. The survey may reveal specific aspects of 
the study that participants dislike, which can inform efforts to improve the experience for 
participants in the future.   
 
10.2.7 Sleep Disorders Questionnaire 
This brief self-report questionnaire will be used to assess Sleep Apnea, REM Sleep Behaviour 
Disorder and Restless Leg Syndrome (RLS). Sleep Apnea will be assessed using questions 
from the Stop-Bang Questionnaire [38]. RBD will be assessed using a single question from the 
Mayo sleep questionnaire: “Have you ever been told, or suspected yourself, that you seem to 
‘act out your dreams’ while asleep (for example, punching, flailing your arms in the air, making 
running movements, etc.)?”[39]. RLS will be assessed using the 8-item Cambridge Hopkins 
Questionnaire [40]. 
 
10.3 
BHPro Outcome Measures 
The following assessments will be completed online directly through BHPro. Participants will 
receive an e-mail notification to login into BHPro to complete the following assessments. 
 
10.3.1 Alzheimer’s Disease Knowledge Scale (ADKS) 
The Alzheimer’s Disease Knowledge Scale is a 30-item, true/false scale that was designed to 
assess knowledge about Alzheimer’s disease among laypeople, patients, caregivers, and 
professionals. It covers risk factors, assessment and diagnosis, symptoms, course, life impact, 
caregiving, and treatment and management [41]. This scale will be completed online within 
BHPro to measure changes in dementia literacy. 
 
10.3.2 The General Self-Efficacy Scale (GSE) 

 
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Self-Efficacy is a concept that refers to one’s global confidence in their ability to cope with 
demanding or novel situations. The General Self-Efficacy scale is a 10-item, 4-point scale which 
measures one’s perceived competence in dealing with a range of stressful or challenging 
situations [42]. The scale will be completed online within BHPro.   
 
10.3.3 Perceptions Regarding Investigational Screening for Memory in Primary Care 
(PRISM-PC)  
Sections B and D of the PRISM-PC questionnaire will be used to assess attitudes toward 
dementia and dementia screening and will be completed online within BHPro. The PRISM-PC 
questionnaire captures participants’ acceptance, perceived harms, and perceived benefits of 
dementia screening [43].  
 
10.3.4 System Usability Scale (SUS)  
The SUS [44] is a simple scale giving a global view of subjective assessments of usability. An 
adapted 11-item version of the SUS will be used to measure usability of BHPro. 
 
10.3.5 Technology Acceptance Model Questionnaire 
A web-based adapted version of the Technology Acceptance Model Questionnaire [45] will be 
used to evaluate user acceptance of BHPro. Questions include attitude, perceived usefulness 
and perceived ease of use of the technology. 
 
11.0 
EARLY DISCONTINUATION PROCEDURES 
Participants are free to withdraw from study participation at any time, for any reason, and 
without prejudice. 
Study Discontinuation for an individual participant may occur in the following circumstances: 
1. Withdrawal of informed consent by the participant. If a study partner withdraws his/her 
willingness to participate, attempts will be made to find a replacement. If a replacement 
study partner is not identified, the participant will continue to be followed in the study and 
assessments completed to the extent possible.  
2. Adverse event or other significant medical condition which, in the opinion of the 
Investigator, render it necessary to remove the individual from study participation. 
3. Any other occurrence that, in the Investigator’s opinion, makes continued participation 
contrary to the participant’s best interests. 
If the site investigator or CCNA Co-Principal Investigator (Co-PI) leadership team discovers 
sufficient reasonable cause for the premature termination of the study, the terminating party will 
provide written notification documenting the reason for study termination. The appropriate 
regulatory agencies and IRB/REB must be notified. 
 
12.0 
ADVERSE EVENTS 

 
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An adverse event (AE) is any untoward medical occurrence in a participant that occurs from the 
time of the baseline visit and up to 30 days after study participation has ended. For the 
purposes of reporting on the CTU study, an AE is defined as any unfavourable or unintended 
sign (e.g., including an abnormal laboratory finding), symptom, or disease associated with study 
procedures that are both non-serious and either temporally or causally related to study 
procedures. Pre-existing conditions, which increase in frequency or severity or worsen in 
nature during, or as a consequence of, a study procedure, may also be considered an AE if it 
meets the definition of being both non-serious and related to a study procedure.  
An AE does not include: 
• Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, transfusion).  
The condition that leads to the procedure is the AE. 
• Situations   where   an   untoward   medical   occurrence   has   not    occurred (e.g., 
hospitalization for elective surgery, social and/or convenience admissions). 
• Worsening of symptoms associated with expected decline in memory or an associated 
co-morbid condition and not related to a study procedure. 
• Those medical or surgical adverse events that are not related to the study procedures 
 
12.1 
Evaluation and Reporting of Adverse Events 
All AEs both non-serious and either temporally or causally related to study procedures (i.e., a 
new event or an exacerbation of a pre-existing condition) that occur from the baseline visit 
and up to 30 days after study participation has ended will be recorded as an AE in LORIS. 
Adverse events that occur prior to the baseline visit will be documented as medical history. The 
Investigator must follow all AEs until the AE resolves, or until the Investigator determines the 
event is chronic or clinically stable. If an AE remains unresolved at the conclusion of 
participation in the BHSP, the Investigator will make a clinical assessment to determine 
whether continued follow-up of the AE is warranted.  
The Investigator should attempt to establish a diagnosis of the event based on signs, 
symptoms and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE and not the individual signs/symptoms. 
12.2 
Assessment of Adverse Events 
All AEs both non-serious and either temporally or causally related to study procedures will be 
assessed by the Investigator and documented in LORIS. Details of the event must include 
the dates of onset and resolution, severity, relationship to study procedures, seriousness, 
whether the event caused the participant to withdraw from the study, and outcome. 
Severity: Severity should be graded and recorded according to the table below. 
 
Severity 
Definition 
Mild 
Awareness of event but easily tolerated 
Moderate 
Discomfort enough to cause interference with usual activity 
Severe 
Inability to carry out usual activity, incapacitating, requires 
medical intervention 

 
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Relationship: The relationship of the AE to study procedures will be determined by the 
Investigator, and assessed using the following definitions: 
Relatedness 
Description 
 
Not Related 
There is no evidence of a causal relationship and a causal 
relationship cannot be reasonably attributed to the study 
procedures. The event is clearly due to non-study causes. 
 
Unlikely Related 
A poor temporal relationship exists between the event onset and 
study procedures. The event could easily be explained by the 
participant’s clinical state, intercurrent illness, or concomitant 
therapies. 
 
Possibly Related 
A relationship between event onset and study procedures 
cannot be ruled out with certainty and the event may be related. 
There is some evidence to suggest a causal relationship but the 
influence of other factors may have contributed to the event, 
such as the participant’s clinical condition or concomitant 
treatment. 
 
Probably Related 
The event is likely related to study participation. There is 
evidence to suggest a causal relationship, such as reasonable 
temporal sequence from procedure. The influence of other 
factors is unlikely. 
Definitely Related 
The event is clearly related to study participation. There is clear 
evidence to suggest a causal relationship. The influence of 
other factors can be ruled out. 
 
These criteria, in addition to good clinical judgment, should be used as a guide for 
determining the causal assessment.  
12.3 
Collection and Reporting of Serious Adverse Events (SAEs) 
All SAEs thought to be unanticipated and related to study procedures must be collected from 
the time of the baseline visit and up to 30 days after study participation has ended.  SAEs will 
be promptly assessed by the Investigator and documented in LORIS as described below.  
In order to meet the requirements for reporting as an SAE in LORIS, an event must meet all 
three criteria as defined below:  
1) Serious 
a. Untoward occurrence that results in death, is a life-threatening situation, requires 
inpatient hospitalization or prolongation of existing hospitalization, results in 
significant disability/incapacity or is a congenital anomaly  
2) Unanticipated 
a. An AE that is not identified in nature, severity, or frequency in the relevant safety 
documents(s) or is not identified as a possible risk in the study protocol or the 
informed consent form  
3) Related to study procedures in the judgement of the Principal Investigator taking into 
account all aspects of the event 

 
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If the Investigator believes that an SAE is related to a study procedure, this should be specified in 
the narrative section of the SAE report. 
SAEs meeting the above definition must be reported in LORIS promptly, but no later than 10 
business days of the Investigator becoming aware of the event.  
 
In addition, Investigators must report SAEs to their local IRB/REB according to local safety 
reporting guidelines for submission of SAEs.  
 
SAE information including event term, start/stop dates, severity, relationship to study 
procedures, whether the event caused the participant to withdraw from the study, and outcome 
will be entered into LORIS as specified in the Study Procedures Manual. 
 
If only limited information on the SAE is initially available, follow-up reporting is required. If an 
ongoing SAE changes in its intensity or relationship to study procedures or if new information 
becomes available, a follow-up SAE report should be entered into LORIS within 10 days of the 
Investigator becoming aware of the updated information using the same procedure used for the 
transmission of the initial SAE and the same event term should be used. All SAEs should be 
followed to resolution or stabilization. For any questions relating to SAEs, please contact the 
CCNA coordinating center via telephone or email at the number listed in the Study Procedures 
Manual.  
13.0 
STATISTICAL CONSIDERATIONS 
13.1 
Sample Size and Power 
 
With a baseline (t1) sample size of 350 participants and an anticipated 20-30% range of drop-
out rates, we will have between 245 (with 30% dropout) and 280 (with 20% dropout) completed 
participants at t2 (end of intervention). All calculations are for 80% power and 5% two-tailed 
alpha. We considered small (d=0.2) and medium (d=0.5) Effect Sizes for 4 different t1-t2 
correlations (rt1-t2) in the primary outcome variable: r=0.2, 0.3, 0.4 and 0.5.  A final sample of 
n=280 will allow us to detect an ES ≥0.2 if rt1-t2≥0.3.  A final sample of n=245 will allow us to 
detect an ES ≥0.2 if rt1-t2≥0.4 (please see Table 1 for required sample sizes, and Appendix 4 for 
supporting formulae). 
 
Table 1: Required sample size to detect ES = 0.2 or 0.5 across a range of rt1-t2 with statistical 
power = 0.8 and two-tailed alpha error = 0.05.   
 
Effect Size (ES) rt1-t2 
n 
0.2 (small) 
0.2 
316 
 
0.3 
277 
 
0.4 
238 
 
0.5 
198 
0.5 (medium) 
0.2 
53 
 
0.3 
46 
 
0.4 
40 
 
0.5 
34 
 

 
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It is estimated that approximately 50% of participants will own a smartphone with internet 
access appropriate for use of the MyCogHealth mobile cognitive assessment (n=175) and an 
additional 150 will be provided with Android devices (total approx. n = 325). 
 
CTU will provide 120 Axivity devices and 60 EEG headbands to be used for the duration of this 
study, which should allow for all participants to participate in recordings at Baseline and Month 
12. Devices will be centrally distributed from SRI to participants.  
13.2 
Analysis Plan 
 
In our one-group pretest-posttest design the major interest is within-person change in the 
primary and secondary outcomes over time (response variables) in the presence of one or more 
explanatory variables that are categorical or continuous. The data will be analyzed using a 
mixed model for repeated measures approach (MMRM). This approach will treat sites and 
participants as random effects, while observational time and their characteristics such as sex 
and age as fixed effects. Potential effect modifications will be examined using this MMRM 
approach with variable selection based on Akaike/Bayesian information criterion.  
 
A more detailed and formal statistical analytic plan (SAP) will be developed and finalized during 
the study. The SAP will include detailed descriptions for evaluating our study outcomes 
including BHPro, cognition, physical activity and sleep, and recruitment metrics. 
 
13.2.1 Sex and Gender Analysis 
Sex-stratification will be used in analyses as appropriate. Where appropriate and available, sex-
specific normative data will be used in the scoring of cognitive tests. In assessing the 
psychometric properties of composites, the cohort will be divided into groups based on sex. 
 
14.0 
RECORDING AND COLLECTION OF DATA 
14.1 
Case Report Form 
See Appendix 5 for the Flow of Data Figure. 
 
14.1.1 Standardized Subject Demographic and Clinical-Research Meta-Data  
Demographic, clinical, and remote assessment data will be entered into the LORIS system.  
 
The Investigator and local site study personnel will be trained on case report form (CRF) and 
electronic case report form (eCRF) completion and data entry into the LORIS system. The 
investigator is responsible for all entries in the CRF/eCRF for completeness, accuracy and 
clarity. The investigator or designee should complete the CRF/eCRF as soon as possible after 
the information is collected. The investigator is responsible to endorse all the information 
recorded in the CRF/eCRF and will provide formal approval of the final submitted data. 
 
14.1.2 Recordings of Remote Study Visits 
The neuropsychological test battery administration at Screening, Baseline, and Month 12 
conducted by video-conference technology (e.g. Zoom) will be recorded to assist with rater 

 
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scoring, to ensure standard administration and scoring, and to help inform the study on 
feasibility of remote administration of the study assessments. Raters will ask the participant for 
permission to record the testing session prior to initiating the recording. If the participant does 
not provide the rater permission to record, the neuropsychological test battery administration will 
proceed without recording. If video recordings are permitted per local site policy, files will only 
be kept for the minimum amount of time required (but no longer than 60 days from the date of 
recording) to allow for review of the files by local site research members and the study 
Supervising Neuropsychologist to ensure accuracy of scoring, completion of study CRFs and 
entry of study data into LORIS. Only the audio-recording file from the recorded sessions will be 
saved and securely stored within the LORIS system. Audio-recordings will be labelled by LORIS 
PSCID and be accessible to study research personnel only for the purposes described above. 
Once analyses for the study are complete, audio recordings will be permanently deleted from 
LORIS. A copy of the de-identified audio-recording will be saved on external hard drive 
(unlinked to the internet) and retained by the study site for the duration required according to 
local IRB/BEB policy and/or other applicable regulatory requirements for storage of study files.  
 
14.1.3 BHPro 
The BHPro website will be hosted on a secure server. De-identified data (linked to LORIS 
PSCID) will be uploaded (API and/or csv.format), processed, and included in the CTU dataset 
for long-term maintenance and secure storage on the LORIS servers. 
 
14.1.4 Online Cognitive Testing 
Results from the MyCogHealth “burst” cognitive testing will be automatically uploaded to a 
secure server maintained by McGill University (and hosted by LORIS) for data management.  
Data will be downloaded by study staff from The Institute on Aging and Lifelong Health 
(University of Victoria, BC) for cleaning and processing. Processed data will be uploaded again 
into LORIS for inclusion in the CTU dataset (See Appendix 5 Figure 2. MyCogHealth Data Flow) 
and for long-term maintenance and secure storage. The MyCogHealth platform will use and be 
maintained by LORIS system administrators with interoperability with the LORIS system for 
secure access to CCNA investigators.  
 
Web servers for the Cogniciti Brain Health Assessment are hosted in Azure App Service, 
including firewalls and secure data transfer between client and server. Results from the 
Cogniciti Brain Health Assessment will be uploaded (csv.format), processed, and included in the 
CTU dataset for long-term maintenance and secure storage on the LORIS servers.  
 
14.1.5 Actigraphy and EEG Recordings 
Actigraphy data will be downloaded from the Axivity devices by study staff for cleaning and 
processing, and then will be uploaded to LORIS servers to be included in the CTU dataset for 
analysis (See Appendix 5 Figure 5. Actigraphy Data Flow), and long-term maintenance and 
secure storage. 
EEG data stored on the CTU-provided iPod will be automatically uploaded to a manufacturer-
supported cloud server at the end of each day’s recording. Data scripts will automatically 
download data files from the manufacturer-supported server to a server at SRI for cleaning and 
processing. Processed data will be uploaded into LORIS to be included in the CTU dataset for 

 
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analysis (See Appendix 5 Figure 6. EEG Data Flow), and long-term maintenance and secure 
storage. 
 
14.1.6 Genomics 
Raw data from genomic analysis and associated sample and experiment metadata will be de-
identified and uploaded to the LORIS molecular database subsystem for long-term maintenance 
and secure storage and sharing. 
 
14.2 
Study Files and Patient Source Documents  
Participant confidentiality is strictly held in trust by the participating investigators, research 
staff, and the sponsoring institution and their agents. This confidentiality is extended to cover 
testing of biological samples and genetic tests in addition to the clinical information relating to 
participants. Authorized representatives of the sponsoring institution may inspect all 
documents and records required to be maintained by the Investigator, including but not 
limited to, medical records (office, clinic or hospital) for the participants in this study. The 
participating site will permit access to such records. Any data, specimens, forms, reports, and 
other records that leave the site will be identified only by a participant identification number to 
maintain confidentiality. 
ICH-GCP guidelines require independent inspection of clinical program activities. Such 
inspections may be performed at any time - before, during and/or after the study. The 
Investigator and study staff are responsible for maintaining the site regulatory file containing all 
study-related regulatory documentation that will be suitable for inspection at any time by CCNA 
and/or its designees. The Investigator understands and agrees to give access to the necessary 
documentation and files. These documents include Investigators’ Study Files, original 
participant clinical source documents generated at the study site, original participant 
electronic documents or completed source document worksheets. The term “original” means 
the first recording of the data. 
Participant clinical source documents may include, but are not limited to, participant 
hospital/clinic records, physicians’ and nurses’ notes, appointment books, laboratory reports, 
Electrocardiograms (ECGs), Magnetic Resonance Imaging (MRI) images, pathology and 
special assessment reports. The Investigator must assure that all original source 
documents are available to support monitoring activities. 
The Investigator will ensure the site regulatory files are maintained, including essential 
documents such as the study protocol and its amendments, IRB/REB and regulatory 
approvals with associated correspondence, informed consents, staff curriculum vitae, 
correspondence, and other appropriate documents. 
14.3 
Rater Training 
Site staff delegated to administer the remote cognitive, functional and behavioral measures will 
be trained on the assessments and certified on these study specific measures that are 
described in Sections 9.0 and 10.0. Additional details of the rater training and certification 
process will be provided to participating sites and outlined in the Study Procedures Manual. 

 
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14.4 
Retention of Data 
After the notification of the IRB/REB regarding the end of the study, the investigator must retain 
all study records (paper and electronic) according to local IRB/REB policy or other applicable 
regulatory requirements. If the investigator retires, relocates or withdraws from the responsibility 
of keeping the study records, custody must be transferred to a person willing to accept the 
responsibility. The CTU leadership team must be notified in writing if a custodial change occurs. 
14.5 
Quality Assurance/Quality Control 
Study data will be entered in the eCRF in LORIS by trained site study personnel. Data validation 
edit checks will be defined and implemented. Inconsistent and questionable data detected 
during the data entry or data validation process will be queried.  
14.6 
Incidental Findings 
Incidental findings that are identified as being medically significant will be addressed by 
participating site Principal Investigators. Any incidental findings identified during data entry into 
LORIS will be flagged for follow-up to the Investigator or site study staff where the participant 
was seen. The site study staff will link the participant code to his or her identity and the finding 
will be passed on to the site Investigator of the participant in question within 24 hours. The site 
Investigator or site physician will be responsible for determining the significance of the finding, 
arranging appropriate follow-up and informing the primary care physician or other health care 
provider (designated by the participant during screening) in writing of the follow-up. The finding 
and its follow-up will be documented and monitored until it has been resolved or as long as the 
participant remains in the study. 
 
15.0 
PUBLICATIONS POLICY AND SHARING OF DATA 
 
In order to access the data generated in this study, researchers must agree to abide by the 
CCNA Publication and Data Access Committee policy, a document prepared by the CCNA 
Publication and Data Access Committee (PDAC), available for download at www.ccna-ccnv.ca. 
The PDAC consists of a Chair and up to 10 CCNA members. The PDAC members list is 
available upon request. Access to and analyses of CTU-acquired data, stored in LORIS, may be 
granted to qualified persons 12 months (quarantine period) after the principal paper(s) 
answering primary research questions is/are published. A list of CTU protected planned projects 
and publications to be undertaken by the CTU Co-PIs, co-investigators or SC members will be 
posted in the LORIS publication module. Any CTU investigator who worked on the project and 
wishes to analyze and subsequently publish data related to a question already listed in the 
“Protected planned projects and publications” will have priority on said project. Any other 
researcher must receive approval to join the designated writing group for that project to avoid 
duplication of the aims and methods of another CTU publication or wait until the “quarantine 
period” has passed. Requests for use of CTU datasets may be made on the LORIS publications 
module and via email to CCNA; Central Administration [ccna.admin@ladydavis.ca]. 
Investigators will only be granted access to data related to the project outlined in the data 
access request.  
 
Prior to submission for publication or for presentation of any data or results obtained in this 
study, notification to the PDAC is required. Draft manuscripts, abstracts and presentations 
should be submitted to the PDAC for administrative review. The participating sites will retain the 

 
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ownership of their data obtained in this study. No researcher shall include identifiable personal 
health information in any publication or presentation. Authorship of publications resulting from 
this study should accurately reflect the academic contribution of individuals to the design and 
implementation of the trial, analysis of the data and preparation of the manuscript. Funding of 
CTU and CCNA by CIHR and other funding partners must be acknowledged. All publications 
that arise from the use of CTU data will give acknowledgement, attribution, or co-authorship as 
appropriate in accordance with the International Committee of Medication Journal Editors 
(ICMJE) standards and any rules established by the PDAC. 
 

 
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16.0 
REFERENCES 
 
1. 
Alzheimer Society of Canada. Report summary: Prevalence and monetary costs of 
dementia in Canada (2016): a report by the Alzheimer Society of Canada, in Health 
Promot Chronic Dis Prev Can. 2016. p. 231-232. 
2. 
Williamson, J.D., et al., Effect of Intensive vs Standard Blood Pressure Control on 
Probable Dementia: A Randomized Clinical Trial. JAMA, 2019. 321(6): p. 553-561. 
3. 
Fitzsimmons, S. and L.L. Buettner, Health promotion for the mind, body, and spirit: a 
college course for older adults with dementia. Am J Alzheimers Dis Other Demen, 2003. 
18(5): p. 282-90. 
4. 
Anstey, K.J., et al., Body brain life: A randomized controlled trial of an online dementia risk 
reduction intervention in middle-aged adults at risk of Alzheimer's disease. Alzheimers 
Dement (N Y), 2015. 1(1): p. 72-80. 
5. 
Livingston, G., et al., Dementia prevention, intervention, and care. Lancet, 2017. 
390(10113): p. 2673-2734. 
6. 
Ostbye, T. and E. Crosse, Net economic costs of dementia in Canada. CMAJ, 1994. 
151(10): p. 1457-64. 
7. 
Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines. 2019, WHO 
Guidelines Approved by the Guidelines Review Committee: Geneva. 
8. 
Stern, Y., et al., Whitepaper: Defining and investigating cognitive reserve, brain reserve, 
and brain maintenance. Alzheimer's & Dementia, 2018. 
9. 
Editorial, www.thelancet.com/neurology Vol 16 September 2017. 
10. 
The National Academies of Sciences, Engineering, and Medicine. Preventing Cognitive 
Decline 
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Dementia: 
A 
Way 
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http://nationalacademies.org/hmd/reports/2017/preventing-cognitive-decline-and-
dementia-a-way-forward.aspx. 2017. 
11. 
Radd-Vagenas, S., et al., Effect of the Mediterranean diet on cognition and brain 
morphology and function: a systematic review of randomized controlled trials. The 
American journal of clinical nutrition, 2018. 107(3): p. 389-404. 
12. 
Wirth, M., et al., Gene-environment interactions: lifetime cognitive activity, APOE 
genotype, and beta-amyloid burden. J Neurosci, 2014. 34(25): p. 8612-7. 
13. 
Lampit, A., H. Hallock, and M. Valenzuela, Computerized cognitive training in cognitively 
healthy older adults: a systematic review and meta-analysis of effect modifiers. PLoS Med, 
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14. 
Northey, J.M., et al., Exercise interventions for cognitive function in adults older than 50: 
a systematic review with meta-analysis. Br J Sports Med, 2018. 52(3): p. 154-160. 
15. 
Kivipelto, M., et al., Risk score for the prediction of dementia risk in 20 years among middle 
aged people: a longitudinal, population-based study. The Lancet Neurology, 2006. 5(9): 
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16. 
Desikan, R.S., et al., Genetic assessment of age-associated Alzheimer disease risk: 
Development and validation of a polygenic hazard score. PLoS medicine, 2017. 14(3): p. 
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17. 
Woodcock, J. and L.M. LaVange, Master Protocols to Study Multiple Therapies, Multiple 
Diseases, or Both. N Engl J Med, 2017. 377(1): p. 62-70. 
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Saville, B.R. and S.M. Berry, Efficiencies of platform clinical trials: A vision of the future. 
Clin Trials, 2016. 13(3): p. 358-66. 
19. 
Fargo, K.N., et al., The crisis in recruitment for clinical trials in Alzheimer's and dementia: 
An action plan for solutions. Alzheimers Dement, 2016. 12(11): p. 1113-1115. 

 
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20. 
Das, S., et al., LORIS: a web-based data management system for multi-center studies. 
Front Neuroinform, 2011. 5: p. 37. 
21. 
Morris, J.C., The Clinical Dementia Rating (CDR): current version and scoring rules. 
Neurology, 1993. 43(11): p. 2412-4. 
22. 
Wechsler, D., Wechsler adult intelligence scale–Fourth Edition (WAIS–IV). San Antonio, 
TX: NCS Pearson, 2008. 22: p. 498. 
23. 
Nasreddine, Z.S., et al., The Montreal Cognitive Assessment, MoCA: a brief screening 
tool for mild cognitive impairment. J Am Geriatr Soc, 2005. 53(4): p. 695-9. 
24. 
Chapman, J.E., et al., Comparing face-to-face and videoconference completion of the 
Montreal Cognitive Assessment (MoCA) in community-based survivors of stroke. Journal 
of Telemedicine and Telecare, 2019: p. 1357633X19890788. 
25. 
Raghavan, N., et al., The ADAS-Cog revisited: novel composite scales based on ADAS-
Cog to improve efficiency in MCI and early AD trials. Alzheimer's & Dementia, 2013. 9(1): 
p. S21-S31. 
26. 
Kaplan, E., H. Goodglass, and S. Weintraub, The Boston Naming Test. Philadelphia: Lea 
and Febiger; 1983, 1983. 
27. 
Benedict, R.H., Brief Visuospatial Memory Test–Revised. Lutz, FL: Psychological 
Assessment Resources. 1997, Inc. 
28. 
Craft, S., et al., Memory improvement following induced hyperinsulinemia in Alzheimer's 
disease. Neurobiol Aging, 1996. 17(1): p. 123-30. 
29. 
Smith, A., Symbol digit modalities test. Manual. Los Angeles: western. Psychol. Serv., 
1982. 
30. 
Delis, D.C., E. Kaplan, and J.H. Kramer, Delis-Kaplan Executive Function System. 2001. 
31. 
Ricker, J.H. and B.N. Axelrod, Analysis of an oral paradigm for the Trail Making Test. 
Assessment, 1994. 1(1): p. 47-51. 
32. 
Troyer, A.K., et al., Development and evaluation of a self-administered on-line test of 
memory and attention for middle-aged and older adults. Frontiers in Aging and 
Neuroscience, 2014. 6. 
33. 
(NACC), 
N.A.s.C.C. 
COVID 
19 
Impact 
Survey. 
2020; 
Available 
from: 
https://www.alz.washington.edu/. 
34. 
Spitzer, R.L., et al., A brief measure for assessing generalized anxiety disorder: the GAD-
7. Archives of internal medicine, 2006. 166(10): p. 1092-1097. 
35. 
Sheikh, J.I., Yesavage, J.A., Geriatric Depression Scale (GDS): Recent findings and 
development of a shorter version, in Clinical Gerontology; A guide to assessment and 
intervention, T.L. Brink, Editor. 1986, The Haworth Press: New York. p. 165-173. 
36. 
Lawton, M.P. and E.M. Brody, Assessment of older people: self-maintaining and 
instrumental activities of daily living. The gerontologist, 1969. 9(3_Part_1): p. 179-186. 
37. 
Ismail, Z., et al., The Mild Behavioral Impairment Checklist (MBI-C): A Rating Scale 
for Neuropsychiatric Symptoms in Pre-Dementia Populations. J Alzheimers Dis, 2017. 
56(3): p. 929-938. 
38. 
Chung, F., H.R. Abdullah, and P. Liao, STOP-Bang questionnaire: a practical approach to 
screen for obstructive sleep apnea. Chest, 2016. 149(3): p. 631-638. 
39. 
Boeve, B.F., et al., Validation of the Mayo Sleep Questionnaire to screen for REM sleep 
behavior disorder in an aging and dementia cohort. Sleep medicine, 2011. 12(5): p. 445-
453. 
40. 
Allen, R.P., et al., Validation of the self-completed Cambridge-Hopkins questionnaire (CH-
RLSq) for ascertainment of restless legs syndrome (RLS) in a population survey. Sleep 
medicine, 2009. 10(10): p. 1097-1100. 

 
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41. 
Carpenter, B.D., et al., The Alzheimer's Disease Knowledge Scale: development and 
psychometric properties. Gerontologist, 2009. 49(2): p. 236-47. 
42. 
Schwarzer, R. and M. Jerusalem, The general self-efficacy scale (GSE). Anxiety, stress 
& coping, 2010. 12(1): p. 329. 
43. 
Boustani, M., et al., Measuring primary care patients' attitudes about dementia screening. 
Int J Geriatr Psychiatry, 2008. 23(8): p. 812-20. 
44. 
Brooke, J., SUS-A quick and dirty usability scale. Usability evaluation in industry, 1996. 
189(194): p. 4-7. 
45. 
Venkatesh, V. and F.D. Davis, A theoretical extension of the Technology Acceptance 
Model: Four longitudinal field studies. Management Science, 2000. 46(2): p. 186-204. 
46. 
Becker, B.J., Synthesizing standardized mean‐change measures. British Journal of 
Mathematical and Statistical Psychology, 1988. 41(2): p. 257-278. 
47. 
Guenther, W.C., Sample size formulas for normal theory t tests. The American Statistician, 
1981. 35(4): p. 243-244. 
 
 
 
 
 

 
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17.0 
APPENDICES 
17.1 
APPENDIX 1: CLINICAL DIAGNOSTIC CRITERIA 
 
Appendix 1A: Clinical Diagnostic Criteria for Cognitively Unimpaired (CU) Individuals: 
1. Normal age-, sex-, and education-
adjusted performance on 
standardized cognitive tests 
Global CDR Score = 0 
 
Logical Memory II Score= 
≥ 9 for 16 or more years 
of education 
≥ 5 for 8-15 years of education 
≥ 3 for 0-7 years of education 
 
MoCA Total Score > 25 
2.  No Subjective Memory Complaint 
Answer “no” to one or both of the following 
questions: “Do you feel like your memory or 
thinking is becoming worse?” and “Does this 
concern you?” 
 
3. Does not meet clinical diagnostic 
criteria for Dementia 
 
DSM-IV 
 
 
 
Appendix 1B: Clinical Diagnostic Criteria for Subjective Cognitive Impairment (SCI): 
1. Normal age-, sex-, and education-  
adjusted performance on standardized 
cognitive tests 
Global CDR Score = 0 
 
Logical Memory II Score= 
≥ 9 for 16 or more years  
of education 
≥ 5 for 8-15 years of education 
≥ 3 for 0-7 years of education 
 
MoCA Total Score > 25 
2. Subjective Memory Complaint: Self-
experienced persistent decline in 
cognitive capacity in comparison with 
a previously normal status and 
unrelated to an acute event  
 
Answer “yes” to both of the following 
questions: “Do you feel like your memory or 
thinking is becoming worse?” and “Does this 
concern you?”  
 
3. Does not meet clinical diagnostic 
criteria for Dementia 
 
DSM-IV 
 
 
 
 

 
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Appendix 1C: Clinical Diagnostic Criteria for Mild Cognitive Impairment (MCI): 
1. Concern regarding a change in 
cognition  
 
 
Report from participant and/or informant 
2. Impairment in one or more cognitive 
domains 
Global CDR Score = 0.5 
 
Logical Memory II Score = 
≤ 8 for 16 or more years of education 
≤ 4 for 8-15 years of education 
≤ 2 for 0-7 years of education 
 
MoCA Total Score 13-24 inclusive 
3. Preservation of independence in 
functional abilities  
 
Lawton-Brody IADL Score > 14/23 
 
4. Does not meet clinical diagnostic 
criteria for Dementia 
 
DSM-IV 
Global CDR Score < 1.0 
 
 
 

 
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17.2 
APPENDIX 2: SCHEDULE OF EVENTS 
 
PROCEDURES 
SCREENING 
(within 21d of 
baseline) 
BASELINE 
(+/- 2 weeks) 
MONTH 3 
(+/- 2 weeks) 
MONTH 6 
(+/- 2 weeks) 
MONTH 9 
(+/- 2 weeks) 
MONTH 12 
(+/- 2 weeks) 
TELE/VIDEO-CONFERENCE REMOTE PROCEDURES1 
INFORMED CONSENT 
X 
SOCIODEMOGRAPHICS 
X 
MEDICAL /SURGICAL/FAMILY HISTORY 
X 
X 
X 
HEIGHT / WEIGHT / BMI2 
X 
 
 
 
 
X 
CLINICAL DEMENTIA RATING (CDR)3 
X 
X 
LAWTON BRODY INSTRUMENTAL ADLs 
X 
 
 
 
 
X 
HEARING AND VISION ASSESSMENT 
X 
 
 
 
 
 
CAIDE SCORE 
X 
X 
REMOTE NEUROLOGICAL EXAM4 
X 
 
 
 
 
X 
FOLLOW-UP PHONE CALL (continued interest, satisfaction 
with BHPro, medical and diagnostic changes5) 
 
 
X 
X 
X 
 
NEUROPSYCHOLOGICAL TEST BATTERY6 
MONTREAL COGNITIVE ASSESSMENT 
X 
 
 
 
 
X 
LOGICAL MEMORY 1 and 2  
X 
 
 
 
 
 
CRAFT STORY 21 Immediate and Delayed Recall AND 
DELAYED RECALL 
X 
X 
ADAS-COG word recall, delayed recall, orientation 
 
X 
 
 
 
X 
BRIEF VISUOSPATIAL MEMORY TEST-REVISED (BVMT-R) 
 
X 
 
 
 
X 
ORAL SYMBOL DIGIT MODALITITES TEST 
 
X 
 
 
 
X 
ORAL TRAIL MAKING TEST A AND B 
 
X 
 
 
 
X 
DKEFS COLOR-WORD INTERFERENCE TEST 
 
X 
 
 
 
X 
DKEFS VERBAL FLUENCY 
X 
X 
BOSTON NAMING TEST (BNT), 15-item 
X 
X 

 
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PROCEDURES 
SCREENING 
(within 21d of 
baseline) 
BASELINE 
(+/- 2 weeks) 
MONTH 3 
(+/- 2 weeks) 
MONTH 6 
(+/- 2 weeks) 
MONTH 9 
(+/- 2 weeks) 
MONTH 12 
(+/- 2 weeks) 
BURST COGNITIVE TESTING7 
 
X 
X 
X 
X 
X 
COGNICITI BRAIN HEALTH ASSESSMENT (BHA)8 
 
X 
 
X 
 
X 
ONLINE FUNCTIONAL AND BEHAVIORAL ASSESSMENTS9 
GERIATRIC DEPRESSION SCALE (GDS) 
 
X 
 
 
 
X 
GENERALIZED ANXIETY DISORDER 7-ITEM SCALE (GAD-7) 
 
X 
 
 
 
X 
MILD BEHAVIORAL IMPAIRMENT CHECKLIST (MBI-C) 10 
 
X 
 
 
 
X 
SLEEP DISORDERS QUESTIONNAIRE 
 
X 
 
 
 
X 
COVID-19 QUESTIONNAIRE 
 
X 
 
 
 
X 
RESEARCH SATISFACTION SURVEY 
 
X 
 
X 
 
X 
OTHER REMOTE DATA COLLECTION AND MONITORING 
ACTIGRAPHY APPLICATION AND DATA COLLECTION11 
 
X 
 
 
 
X 
EEG WEARABLE INSTRUCTIONS AND DATA COLLECTION11 
 
X 
 
 
 
X 
SALIVA SAMPLE COLLECTION12 
 
X 
 
 
 
 
ONLINE BHPro ASSESSMENTS13 
SELF-EFFICACY (The General Self-Efficacy scale, GSE) 
 
X 
 
X 
 
X 
DEMENTIA LITERACY (The Alzheimer’s Disease Knowledge 
Scale, ADKS) 
X 
X 
X 
ATTITUDE TOWARDS DEMENTIA AND DEMENTIA SCREENING 
(Parts B and D of the PRISM-PC Questionnaire)  
X 
X 
X 
USABILITY (web-based version System Usability Scale-
adapted) 
X 
X 
ACCEPTABILITY (Technology Acceptance Model 
questionnaire-adapted) 
X 
X 
BHPro LIFESTYLE RISK QUESTIONNAIRES14 
X 
X 
X 
X 
X 
 
1Procedures and assessments completed by telephone or video-conference between participant, study partner (if applicable) and study site team member.      
2 Height will not be collected at Month 12. 

 
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3 If no study partner/informant available the Global CDR score will be determined by research team consensus using all other available information and best 
clinical judgement  .  
4To be completed by site Principal Investigator or other medically qualified professional following the recommended Telemedicine guidelines for neurological 
exams provided by AAN. 
5Medical and diagnostic changes only to be completed at Month 6 follow-up phone call.  
6Neuropsychological Test Battery to be completed by video-conference between participant and trained rater. Instructions and administration adapted for remote 
use and provided in Study Procedures Manual. 
7Instructions and initial testing for “Burst” Cognitive Testing will be completed during remote baseline video-conference. Participants will receive notification by 
smartphone (for “burst” cognitive testing) and by email to complete other timepoints remotely. The Neuropsychological Test Battery should be completed prior 
to the start of “Burst” Cognitive Testing at Baseline and Month 12.  
8Participants will receive a personalized link sent by the study coordinator to complete the Cogniciti BHA. “Burst” Cognitive Testing should be completed prior to 
the Cogniciti BHA at Baseline, Month 6 and Month 12. 
9Participants will receive a personalized link sent through the LORIS survey tool to complete the behavioral and functional self-report measures. 
10The MBI-C will be completed by Study Partner/Informant if available. 
11Devices and user instructions will be sent to participants from SRI by mail. Application and Instructions on use and duration of Axivity device, and EEG headband 
will be provided by video-conference between participant and SRI study team member. At the conclusion of the specified recording period, devices will be 
returned by mail. The same procedure will be followed for Month 12.   
12A saliva sample with at-home collection kit will be provided for genomics testing (PHS) and analysis.  
13These assessments will be completed online through the BHPro  website. 
14Brief questionnaires based on BHPro content modules that will be completed every 3 months within the online program to evaluate changes in lifestyle risk (e.g. 
sleep, diet, physical activity, vascular risks, social engagement, cognition, vision and hearing; see Appendix 3 for questionnaire descriptions). 

 
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17.3 
APPENDIX 3: BHPro LIFESTYLE RISK QUESTIONNAIRES 
BHPro Module 
Questionnaire Description 
Physical Activity The International Physical Activity Questionnaire -Short Form1 is a brief 
7-item self-report measure that captures types of and intensity of physical 
activity and sitting time daily over the last 7 days. 
Cognitive 
Engagement 
Participants will complete a 6-item questionnaire assessing types and 
duration of cognitive activities2 (e.g. read, watch T.V., socialize).  
Diet 
Participants will complete a shorter version of the Eating Pattern Self-
Assessment Questionnaire developed by CCNA Team 5, which asks 
participants about foods and servings typically consumed over the last 30 
days. 
Sleep 
Brief 10-item self-report questionnaire developed by BHPro Sleep 
Module content leads that assesses sleep duration, sleep patterns and 
difficulties and daytime fatigue over the past 3 months. 
Social and 
Psychological 
Health 
An 8-item questionnaire comprising 1 item on loneliness adapted from 
CLSA, 1 item on ageism adapted from the European Social Survey3, 1 
item on subjective age adapted from the MIDUS study4, 1 item on 
essentialist beliefs of aging from Weiss et al., 20195, and 4 items on 
depression, anxiety, stress, and social support from STOP-D6. 
Vascular Health  
12-item self-report questionnaire developed by the BHPro Vascular 
Health team based on the American Heart Association's Life's Simple 
Seven checklist of the main risk factors for heart disease and stroke. 
https://www.heart.org/en/healthy-living/healthy-lifestyle/my-life-check--
lifes-simple-7 
Vision and 
Hearing 
10-item questionnaire developed by BHSP Vision and Hearing Module 
content leads that assesses perceived visual and auditory ability and 
actions taken to address potential vision/hearing difficulties.  
References: 
1. Lee, P.H., et al., Validity of the international physical activity questionnaire short form (IPAQ-SF): 
A systematic review. International Journal of Behavioral Nutrition and Physical Activity, 2011. 8(1): 
p. 115. 
2.  Vemuri, P., et al., Effect of lifestyle activities on Alzheimer disease biomarkers and cognition. Annals of neurology, 
2012. 72(5): p. 730-738. 
3.  Bratt, C., et al. Perceived age discrimination across age in Europe: From and ageing society to a society for 
all ages. Developmental psychology, 2018. 54(1): p. 167-180. 
4.  Mock, S.E., & Eibach, R.P. Aging attitudes moderate the effect of subjective age on psychological well-
being: Evidence from a 10-year longitudinal study. Psychology and aging, 2011. 26(4): p. 979-986. 
5. Weiss, D., Reitz, A.K., & Stephan, Y. Is age more than a number? The role of openness and (non) 
essentialist beliefs about aging for how young or old people feel. Psychology and aging, 2019. 34(5): p. 729-
737. 
6. Young Q.-R., Ignaszewski, A., Fofonoff, D., & Kaan, A. Brief screen to identify 5 of the most common forms 
of psychological distress in cardiac patients: Validation of the screening tool for psychological distress. 
Journal of Cardiovascular Nursing, 2007. 22(6): p. 525-534. 
 
 
 
 

 
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17.4 
APPENDIX 4: SAMPLE SIZE CALCULATION FOR ONE-GROUP PRE-TEST POST-
TEST DESIGN 
 
Sample size/power calculation was done based on effect size for one-group pre-/post design. 
According to  Becker [46], the effect size (ES) for such a design should be defined as, assuming 
SD at pre- and post-test are equal, 
 
ES= mean change
SD baseline =
mean change
SD change /ඥ2(1 −𝑟𝑟)
 
 
where r is correlation between pre- and post-scores. Note that 
var(mean change) = 2var(baseline)(1 −r) 
 
 
Sample size can then be done based on the following test statistic 
𝑇𝑇= mean change
SD change/√𝑛𝑛=
ES
ඥ2(1 −𝑟𝑟)/𝑛𝑛
 
 
 
i.e., The corresponding sample size formula for 80% power at 5% significance level is given by: 
 
𝑛𝑛= 
(1.96 + 0.84)2 
(mean change/SD change)2 + 2 = (1.96 + 0.84)2
ES2/[2(1 −𝑟𝑟)]
+ 2 
 
Note that plus 2 (≈2 × 1.962) is to approximate the Z-test with a sample size calculated for the 
t-test [47].   
 
Therefore, the sample sizes for detecting small and moderate magnitudes of ES 3 at 2-sided 
5% significance level with 80% power are given below for values of correlation r 
 
ES 
r 
n 
0.2 (small) 
0.2 
316 
 
0.3 
277 
 
0.4 
238 
 
0.5 
198 
0.5 (medium) 
0.2 
53 
 
0.3 
46 
 
0.4 
40 
 
0.5 
34 
 
 
 
 
 
 
 
 

 
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17.5 
APPENDIX 5: CTU FLOW OF DATA FIGURES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 1. Overview of CTU Flow of Data into LORIS 

 
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Figure 2. Brain Health PRO Data Flow 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study coordinator 
logs into admin 
portal in Brain Health 
PRO and enters 
participant LORIS 
PSCID and e-mail to 
link data with CTU 
data.  
Participant registers 
for Brain Health PRO 
using e-mail address 
(user name) and 
password. E-mail 
address will be used to 
send weekly updates 
to participant 
Participant will enter 
a preferred first 
name that will be 
displayed on the 
home 
page/navigation 
screen each time 
they log in to Brain 
Health PRO 
This completes first-
time registration in 
BHPro. For each 
subsequent visit to 
the BHPro online 
program, the 
participant will login 
in with user name 
(email) and password 
only. 
De-identified data 
(linked to LORIS 
PSCID) 
temporarily 
stored on web 
developer server 
will be uploaded 
to LORIS 
(csv.format). 
LORIS team 
performs QC check 
and uploaded de-
identified 
processed data for 
inclusion in CTU 
dataset 
 
Study coordinator 
registers participant in 
LORIS generating a 
unique participant 
study ID (PSCID).  

 
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MyCogHealth
study team installs 
app and registers 
participant using a 
pseudo email and 
password
Study coordinator 
completes 
registration 
process by 
entering LORIS 
PSCID in lieu of 
First (site number) 
and Last Name 
(subject number)  
from the app's 
main menu under 
"My Account"
Participant 
opens the 
MyCogHealth 
app for 1st time 
during zoom call 
with study 
coordinator and 
completes 
training session 
followed by 6 
days of testing
Participant-
completed 
MyCogHealth 
data is 
electronically 
and 
automatically  
uploaded to 
McGill server 
hosted by 
LORIS
De-identified 
MyCogHealth 
data is stored 
on McGill 
server for the 
duration of 
the study
Data is 
downloaded 
from McGill 
server to a 
secure UVic 
Server 
through the 
MyCogHealth 
Research 
Portal  for 
cleaning
Cleaned 
MyCogHealth 
data is merged 
into the CTU 
dataset on 
McGill server 
and stored 
permanently  
beyond study 
completion
Figure 3. MyCogHealth Data Flow: Participant 
Using Phone Provided by CTU 
 

 
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Figure 4. MyCogHealth Data Flow: Participant 
Using Phone Not Provided By CTU 
 
During Zoom call with 
study coordinator, 
participant is 
instructed on how to 
download the 
MyCogHealth app from 
the Google Play Store 
or Apple Store 
Participant signs up for 
a new account on the 
MyCogHealth app. 
Study Coordinator 
instructs participant to 
register using a pseudo 
email (a unique list of 
pseudo emails is 
provided to each study 
site by the 
MyCogHealth Research 
Team
Participant is instructed to 
complete the registration process 
by entering LORIS PSCID in lieu of 
First (site number) and Last Name 
(subject number) under 
"Additional Information" 
Participant opens 
the MyCogHealth 
app during the Zoom 
call with study 
coordinator and 
completes training 
session followed by 
6 days of testing 
Participant-
completed 
MyCogHealth data is 
electronically and 
automatically  
uploaded to McGill 
server hosted by 
LORIS 
Cleaned 
MyCogHealth data is 
merged into the CTU 
dataset on McGill 
server and stored 
permanently  
beyond study 
completion 
Data is downloaded 
from McGill server to 
a secure UVic Server 
through the 
MyCogHealth 
Research Portal for 
cleaning 
De-identified 
MyCogHealth data is 
stored on McGill 
server for the 
duration of the study 

 
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Figure 5. Actigraphy Data Flow 
 
 
 
 
 
Figure 6. EEG Data Flow 
 
 
 
 
 
With instruction from study 
staff at SRI, participant puts 
on the Axivity (no need to 
activate or push any 
buttons)
Data collected for each 
participant is stored on 
the device until its return 
to SRI at end of the 14-
day recording period at 
Baseline and Month 12  
Data from device is 
downloaded by SRI 
study staff and 
uploaded to LORIS (cwa 
format) along with 
sleep and work diary 
(pdf format)
SRI team downloads 
from LORIS, performs QC 
check of data and 
uploads processed file to 
LORIS for inclusion in 
CTU dataset
With instruction from study 
staff at SRI, participant 
turns on the EEG headband 
and initiates recording via 
the app on the study 
provided iPod
Participant must end the 
recording  each morning 
and charge the device 
until a total of 3 
recordings complete at 
Baseline and Month 12. 
Data collected during that 
interval is automatically 
uploaded to a 
manufacturer supported 
cloud server at the end of 
each day's recording
Data script 
automatically 
downloads data file 
from company server to 
a server at SRI
SRI team performs QC 
check of data and 
uploads file (edf format)
to LORIS for inclusion in 
CTU dataset

 
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17.6 
APPENDIX 6: OPTIONAL CARDIOPULMONARY SENSOR SUB-STUDY 
 
As part of an optional sub-study with a separate consent form, cardiopulmonary measurements 
(respirations, ECG, blood pressure) will be recorded for 24-hours at Baseline and Month 12 
using a set of two water-resistant sensors attached to the sternum using ultrasound gel or 
adhesive and Tegaderm and to the index finger of the non-dominant hand using a Velcro band 
(ANNE sensor suite, Sibel Health, Chicago, USA). The chest sensor is a 4.4x2.4x0.5cm silicon-
encased flexible waterproof adhesive that contains a triaxial accelerometer, 3-axis gyroscope, 
thermometer, and surface electrodes for bioimpedance from which ECG, respiratory 
movements, and temperature can be derived. The finger sensor is a 4.7x2.5x0.5cm silicone-
encased flexible waterproof strip that wraps around the finger and allows for measurement of 
pulse oximetry and temperature.   
After study equipment and materials are shipped to and received by the participant, study staff 
will instruct the participant on the proper application and use of the ANNE Vital Sign System 
over remote video-conference. Specifically, study staff will instruct the participant to affix the 
ANNE Vital Sign System chest sensor to the participant’s chest using ANNE hydrogel adhesive 
and a clinical waterproof 3M Tegaderm dressing. Next, study staff will instruct the participant to 
affix the ANNE Vital Sign System finger sensor to the participant’s dominant index finger using 
the ANNE strap (fabric wrap). Participants will wear the sensors for 24 hours before removing it 
themselves at home and shipping back to Sunnybrook Research Institute using a pre-paid, pre-
addressed package. This procedure will be completed at the Baseline visit and repeated 12 
months later. 
Cardiopulmonary data – .shrd file type – from the ANNE Vital Sign System will be downloaded 
via Bluetooth locally to an iOS tablet, then converted to .edf file type, and manually annotated to 
extract information on sleep apnea. SRI will then upload de-identified processed data and 
summary measures to the Longitudinal Online Research and Imaging System120 (LORIS) 
using the media uploaded functionality. All uploads and downloads will be by Secure File 
Transfer Protocol (SFTP).