The Brain Health Champion Study: Promoting Non-pharmacological Interventions in Cognitive Disorders and Those at Risk
Phase: NA
Conditions: Mild Cognitive Impairment, Dementia, Mild, Subjective Cognitive Decline, At Risk for Cognitive Decline
Sponsor: Brigham and Women's Hospital

1 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
DETAILED PROTOCOL  
NCT Number:  
NCT03772977 
 
Title: 
The Brain Health Champion study:  Promoting non-pharmacological interventions in 
cognitive disorders 
 
Study Sponsor: 
The Alzheimer Innovation Fund at Brigham and Women’s Hospital, Vettel Family 
Ann Romney Center for Neurologic Diseases 
 
Study Principal Investigator: 
Seth A. Gale, M.D. 
 
Co-Principal Investigator: 
Kirk R. Daffner, M.D. 
 
Co-Investigators: 
Diler Acar, M.D. 
Taylor Krivanek, B.A. 
Brittany McFeeley, B.S. 
Casey Nicastri, B.S. 
Scott McGinnis, M.D. 
Kim Willment, Ph.D. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
 
 
 
 
 
 
 
 
I. 
BACKGROUND AND SIGNIFICANCE  
 
Despite ongoing efforts for improvement, health care for persons with cognitive 
disorders and those at-risk remains inconsistent, often suboptimal, and largely 
unplanned (Odenheimer, 2013). Providing optimal care for patients with these 
conditions is challenging and critically important, given the myriad benefits that optimal 
care provides for patients and their families and for the health care system as a whole. 
For example, the estimated, total cost of health care, including long term care and 
hospice care, for Alzheimer disease (AD) in the United States alone was $236 billion 
dollars in 2016, close to 10% of all health care expenditures (Alzheimer Facts and 
Figures, 2016). 
 
There have been several initiatives to identify what interventions constitute “optimal 
care” for patients with dementia. An effort led by the American Academy of Neurology 
(AAN) and the American Medical Association-convened Physician Consortium for 
Performance Improvement (PCPI), identified a set of 10 dementia care quality 
measures, derived from expert consensus, that providers and health systems should 
strive to achieve for these patients (Odenheimer 2013).   
 
One of these measures, entitled “Caregiver Education and Support”, encourages the 
education of patients and caregivers on aspects of disease management, with a focus 
on promoting health behavior changes and referral to additional resources to achieve 
these changes.    
 
Meeting this particular measure of quality dementia care comprehensively is 
challenging. While it is simple for providers to introduce the importance of certain 
health behavior changes at an initial visit, and then reinforce recommendations every 
3-6 months in longitudinal follow-up, this treatment plan often does not lead to 
sustained behavior changes. Importantly, there are no such care quality measures for 
patients who are cognitively normal but at-risk for dementia. 
Providing the care and treatment plan that is probably needed for many patients to 
make long-term changes is hindered by a number of factors.  Structural factors include 
an overall health system which dis-incentivizes clinicians from carrying out regular, 
“face-to-face” or electronic encounters with these medically complex patients. These 
encounters are critical to re-enforce education and to successfully promote adoption 
and long-term maintenance of brain healthy behaviors. Institutional barriers include the 
fact that many hospitals or individual clinics employ clinicians who have inadequate 

3 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
professional time or training/skill-sets in the domain of motivating for behavior change. 
Finally, disease-specific factors include a high prevalence of neuropsychiatric 
symptoms among patients, including apathy and depression, and high rates of 
caregiver “burnout” and health problems, all of which directly impact patient behavior. 
Clinical research has provided an abundance of evidence that even short-term 
adherence (6-months or less) to regimens of aerobic exercise, socially and mentally 
stimulating activities, and a “brain healthy” diet improves various health and quality-of-
life outcomes for patients with cognitive disorders and their caregivers (Sobol, 2016; 
Dannhauser, 2015). In addition, for cognitively normal individuals with risk factors for 
dementia and individuals with subjective cognitive complaints (who do not yet have the 
underlying disease), there is ample evidence that participation in brain healthy 
behaviors decreases the incidence of dementia and improves overall cognitive 
functioning, quality of life, and other outcomes (Beckett, 2015; Ngandu et al., 2015; 
Okereke et al., 2012; Smith 2016; Wilson et al., 2002).  
The benefits of tele-health and e-health programs, as well as motivational “booster” 
sessions to reinforce education and recommendations, have become increasingly 
recognized in different practice settings. Recent reviews support that notion. For 
example, tele-health delivered interventions for physical activity and dietary behavior 
change are successful in promoting short- and long-term behavioral changes (Goode, 
2012).    
For neurocognitive disorders, many of these programs have focused on psychosocial 
education for caregivers, which includes strategies to help patients maintain autonomy 
in daily activities and to meet patients’ and caregivers’ complex needs. For example, a 
recent tele-health program for caregivers employed a 14-week behavioral intervention 
using video instructional materials, workbook and telephone coaching in behavioral 
management, “pleasant events” scheduling, and relaxation (Steffen et al, 2016).   
Fewer studies have primarily focused on patient adoption and maintenance of the 
evidence-based brain healthy behaviors which is the primary aim of the Brain Health 
Champions (BHC) program.  One study engaged patients with MCI in a complex 
intervention for 12 weeks, including physical activity, group-based cognitive stimulation, 
and individual cognitive stimulation, and showed notable treatment effects in aspects of 
cognition, physical health (e.g., blood pressure, BMI), and fitness level (Dannhauser  
2014).  There is a clear need to improve the adherence to evidence-based brain 
healthy recommendations among patients with dementia and those at risk.  
 
Finally, important to this proposed study, though these programs are not yet common 
in dementia care settings, there is strong evidence of interest from patients and their 
caregivers to participate in programs like BHC (Dal Bello Has et al, 2014). 
   
 
II. 
SPECIFIC AIMS 

4 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
 
The overall objective of this research is to investigate what clinical programs may be 
best for the delivery of optimal dementia care and dementia risk reduction at the BWH 
Alzheimer Center and BWH primary care centers. This particular study is designed to 
adapt the evidence-supported practice of employing frequent encounters in-between 
clinic visits, which has been effective in other diseases, to dementia care. The practice 
has been developed in to a clinical care program we have called the Brain Health 
Champion (BHC) program. 
Adoption and maintenance of brain healthy behaviors is one of several, consensus-
driven measures which, when met, can have a meaningful impact on quality of life and 
the burdens of disease (Odenheimer 2013).   
Our hypothesis is that patients who engage in frequent, motivational encounters 
between a clinician at the Alzheimer Center treatment team for 6 months, whether by 
telephone, video, or e-correspondence, and in-person or virtual visits (i.e., BHC), will 
lead to a 25% greater change in participation in brain healthy activities compared to 
patients receiving current clinical care (i.e., physician counseling and education, or 
PCE).   
These are more specific aims of the research: 
1) To investigate whether augmenting the current clinical care in an academic, 
cognitive neurology center or primary care center with a health behavior 
intervention will improve patient adoption and maintenance of treatment 
recommendations. 
2) To investigate whether such a care program might improve other health 
outcomes, including: patients’ cognitive performance, sleep, daily 
functioning, quality of life measures, the utilization of health services and 
aspects of neuropsychiatric health.  
3) To investigate the feasibility, ease of use, and benefit for behavior change of 
the employed mobile health platforms, Fruit Street, Fitbit, and MealLogger 
Pro. 
4) To measure whether additional, motivational “booster sessions”, for 6 
months following the 6-month intervention, improve maintenance of brain 
health behavior changes made during the intervention period.  
 
III. 
SUBJECT SELECTION 
 
We aim to have 85 subjects complete the study.    
 
A. Overall enrollment criteria: 
 
Inclusion: 
 
All participants: 

5 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
 
1) Age 60-79 
2) Existing patient at Brigham Health system with at least one prior visit with providers 
and plans to establish/continue longitudinal care 
3) Proficiency in English 
4) In adequate physical health, as determined by participant’s physician-provider, to 
safely complete participate the physical exercise encouraged by the study 
5) Willing to complete all study-related activities for 12 months 
6) Willing to be randomized to either lifestyle intervention group 
7) Willing and able to travel to the Brigham and Women’s Hospital (Boston) regularly 
OR  
Access to a smartphone and/or computer with webcam and stable internet access 
 
 
Neurology participants:  
 
1) Have a diagnosis of Mild Cognitive Impairment (MCI) due to Alzheimer disease 
(AD), cerebrovascular disease (CVD), or mixed-type AD/CVD with an MMSE 
guideline) 24-30, or mild dementia due to AD, CVD, or mixed-AD/CVD with an 
MMSE guideline 20-30. In some cases, based on the clinical judgment of the 
treating neurologist, patients who score outside of these guidelines on the MMSE 
may be enrolled, as diagnosis does not always correlate to MMSE score 
2) Telephone Interview for Cognitive Status (TICS-40) greater than 20  
3) A reliable study partner (in subjects with mild dementia, this will be the caregiver) 
needs to be identified who can complete questionnaires every 6 months about 
participant’s cognition/daily functioning, and, communicate regularly with study 
personnel about participant’s activities, health, and safety 
 
 
Primary Care “At risk” participants:  
 
1) Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia 
risk score of ≥ 6, or score of 5 plus one of the following: a history of ADRD in a first-
degree relative, or type II diabetes or “pre-diabetes” spectrum (A1C level ≥ 5.7) 
2) Telephone Interview for Cognitive Status (TICS)-40 greater than 31 
3) AD8 score less than or equal to 2  
4) A reliable study partner (e.g. family member) needs to be identified who can 
complete questionnaires every 6 months about participant’s cognition/daily 
functioning 
Exclusion: 
 
All participants: 
 
1) Current levels of aerobic physical activity that cause sweating or breathlessness at 
least twice a week, lasting 20-30 minutes (consistent with “high” physical activity 
level, per the CAIDE risk score) 
2) Score greater than or equal to 2 standard deviations below age- and education-
adjusted norms on two or more tests in the cognitive battery (PACC-BHC)  

6 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
3) Current significant or unstable medical, neurologic or psychiatric illness, that 
impairs mobility, mild to moderate aerobic exercise capacity, or daily functioning 
4) Significant cardiovascular disease (including NYHA Class III or IV congestive heart 
failure, clinically significant aortic stenosis, history of cardiac arrest, or uncontrolled 
angina)  
5) Serious conduction disorder (e.g., 3rd degree heart block) or uncontrolled 
arrhythmia  
6) Myocardial infarction, major heart surgery (i.e., valve replacement, bypass surgery, 
stent placement, angioplasty), deep vein thrombosis, or pulmonary embolus in the 
past 6 months  
7) Lung disease requiring either regular use of corticosteroids or the use of 
supplemental oxygen (inhaled steroids for asthma is permissible) 
8) Significant neurologic disease, including any form of Parkinson disease, Huntington 
disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear 
palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of 
significant head trauma with persistent neurologic sequelae or known structural 
brain abnormalities 
9) Large vessel stroke in the past 2 years 
10) History of TIA or small vessel stroke in the last 6 months 
11) History of alcohol or substance abuse or dependence within the past 2 years, as 
per DSM-5 criteria  
12) Geriatric Depression Score (GDS) ≥ 10, unless deemed by treating provider not to 
have active depression (e.g. adjustment disorder, grief reaction) 
13) Concerns of the participating PCP or neurologist about health risks for subject 
participation, or, if a subject is physically unable to carry out recommendations 
14) Resides in an assisted living facility or nursing home 
15) Life expectancy of < 2 years 
16) Current participation in a pharmacological or other interventional AD trial 
 
The PI (Dr. Gale), in consultation with participating providers, will have ultimate 
discretion regarding including or excluding participants based on clinical factors. 
 
All patients will receive physician counseling and education (PCE) through the 
Alzheimer Center or primary care center. PCE includes, but is not limited to, 
management of appropriate medications, education about evidence-based, non-
pharmacologic behavioral interventions, counseling on caregiver behavioral and 
support strategies, and referrals to social workers and other providers, if warranted.  
 
It is likely that family members or other caregivers will play an active role in the study, 
especially for subjects who are at later stages of MCI due to AD and mild AD dementia.  
In every case, the clinical team will assess a new subject’s executive and decision-
making capacity to understand and carry out the study on his/her own. If the clinical 
team is comfortable with the subject’s capacity to do so, then the involvement of a 
caregiver is not required. For subjects who enroll without the daily involvement of a 
caregiver, the clinical team may require the involvement of such a person, at any time 
through the course of the study, if they identify a decline in the participant’s capacity to 

7 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
safely and optimally carry out the study procedures on their own. 
 
B. Subject selection, Step 1: Electronic medical record (EMR) search 
 
The first step in subject selection will be a strategic search of the EMR conducted 
by study personnel. All potential subjects will be age 60-79, will be established 
patients of the Brigham Health system, and ideally will have indicated interest in 
participation in research through registration or intake to their clinic. Treating 
neurologists will identify possible neurology participants during their clinical 
interviews, either prior to or during a routine follow-up appointment or during that 
appointment. To screen for potential primary care “At-risk” participants, medical 
records of patients with upcoming appointments in Brigham Primary Care will be 
screened using EPIC research reports, extracting the following data: last blood 
pressure (systolic BP >140), body-mass index (BMI >30 kg/m2), last A1C level 
(A1C level ≥ 5.7), and total serum cholesterol (cholesterol >250 mg/dl). These 
conditions are part of the calculation of the Cardiovascular Risk Factors, Aging, and 
Incidence of Dementia (CAIDE) risk score (see details, below) (Kivipelto et al., 
2006).  
 
After running the research report, records will be manually screened for family 
history of ADRDs or exclusionary medical conditions. Primary care patients with at 
least one of these risk factors will be eligible for further screening, by telephone 
(see below). After identifying potential participants for telephone screening, 
personnel will communicate with individuals’ primary providers to determine if they 
can safely participate, considering any physical limitations and other 
medical/psychosocial concerns.  
 
 
C. Subject selection, Step 2: Letter and telephone screening 
 
If providers concur that selected participants are eligible for the study, study 
personnel with send a letter (“BHC Prescreening Letter, At-Risk”, submitted) 
electronically (by the Gateway portal) and by mail, to patients, and follow-up with a 
screening telephone call to gauge interest in research (see “Telephone Script, At-
Risk”).  
 
For potential neurology participants: During phone screens, personnel will introduce 
the study, gauge interest, inquire about a reliable study partner to complete 
functional assessment questionnaires and support participant behavior change 
during the trial, and assess the current amount of physical activity. Engagement in 
aerobic activity ≥2 times per week, lasting at least 20-30 minutes will be considered 
a “high” exercise level and be exclusionary. If these criteria are met, personnel will 
then administer the Telephone Interview for Cognitive Status (TICS)-40, an 11-
question validated tool with a maximum score of 40. Potential neurology 
participants must score ≥20.  
 

8 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
For potential primary care participants: During phone screens, personnel will 
introduce the study, gauge interest, and inquire about the availability of a person 
(e.g. family member) who can periodically complete functional assessment 
questionnaires over the two-year trial. Personnel will also assess educational 
attainment, and physical activity level, which are not generally available in the EMR, 
to calculate CAIDE dementia risk score. The CAIDE score ranges from 0 to 15, and 
accounts for age, sex, blood pressure, BMI, educational attainment, cholesterol 
level, and degree of physical activity. Because all participants in the study will be at 
least 60 years old, they will start with a CAIDE score of 4. Consistent with CAIDE, 
engagement in aerobic activity ≥2 times per week, lasting at least 20-30 minutes 
will be considered a “high” exercise level and be exclusionary. Eligible participants 
must have a CAIDE score of ≥ 6 or a CAIDE score of 5 plus one of the following: a 
history of ADRD in a first-degree relative or, type II diabetes or “pre-diabetes” 
spectrum (A1C level ≥ 5.7) (CAIDE+).  
 
If CAIDE+ criteria are met, personnel will administer the (TICS)-40 and AD8, an 8-
point scale for detecting functional abilities. Potential at-risk participants will be 
eligible if they score ≥31 on the TICS and £ 2 on the AD8, indicating well-preserved 
functioning in activities of daily living. An additional level of screening will occur 
during baseline assessments: If participants score ³2 standard deviations below 
age- and education-adjusted norms on two or more tests in the cognitive battery, 
they will be excluded. If at-risk patients score worse than the cut-off values on the 
phone screen (TICs or AD8), or on the in-person neuropsychological tests, their 
PCPs will be informed, allowing them to determine if further clinical evaluation is 
warranted. 
 
All eligible participants: If eligible, personnel will schedule an in-person enrollment 
visit with the participant and study partner (if applicable) on the day of their next 
provider appointment.  
 
When an in-person visit is not possible, personnel will schedule a virtual enrollment 
visit on Enterprise Zoom with the participant and study partner. If possible, this visit 
will take place on the day of their next provider appointment. Instructions for 
accessing Zoom will be sent to the participant via their preferred contact method 
(i.e., Gateway, secure email, or unencrypted email). If potential participants prefer to 
correspond via unencrypted email, study personnel will gain verbal consent during 
the phone screen (see Telephone Script). Prior to virtual enrollment visits, the 
Informed Consent Form will be sent electronically for participants to review via 
REDCap survey link. 
 
IV. 
SUBJECT ENROLLMENT 
 
At the follow-up appointment, the informed consent process will occur after the clinician 
has completed his/her usual PCE for the patient and their condition. In cases where 
time does not allow for consenting and enrollment at the follow-up, interested patients 
will be offered a separate appointment with the study staff to complete the enrollment 
procedures. It is not feasible or necessary to allow for the typical, recommended time 

9 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
of 12 hours following informed consent to enroll subjects in this study for two reasons: 
1) The study is designed to examine a direct extension of clinical care and a separate, 
research-dedicated visit to re-review the study procedures is not feasible within the 
Center’s clinical infrastructure, and, 2) the procedures of the intervention arm pose very 
minimal risk, and the clinical team is well-poised to determine their established 
patient/partner’s level of comprehension of the study during the visit. In addition, in 
most cases, participants have been contacted prior to the informed consent discussion 
by a letter and telephone call, which will allow time for additional consideration.   
When in-person visits are not possible, all consent procedures will occur electronically. 
At the beginning of the virtual visit, study staff will conduct the consenting discussion. 
The participant will sign the consent form in REDCap using Partners REDCap e-
Consenting tool.  
Following the informed consent, subjects will be randomized in REDCap to either the 
physician counseling and education (PCE) or the Brain Health Champion (BHC) 
treatment arm. The randomization schedule in REDCap is hidden from investigators 
and was randomly generated in Excel as a 1:1 allocation. Randomization is stratified 
by diagnosis (MCI or at-risk), using block sizes of 4. Informed consents forms can be 
either mailed or emailed via REDCap link (with verbal consent for unencrypted email 
obtained during telephone screening) to participants, to review prior to visits and to e-
sign following the screening visit, if desired.  
After target enrollment has been reached, we will assign additional participants to the 
BHC and PCE arms as needed to replace participants who have withdrawn from the 
study (were unwilling or unable to complete the protocol), matching based on at-risk 
status or diagnosis of MCI. We will use a separate informed consent to enroll patients 
who will assigned rather than randomized.  
For cognitively impaired participants, the treating neurologist, who has an established 
relationship with the patient and his/her caregiver, having seen them for at least one 
prior appointment at the Alzheimer Center, will decide whether the patient has capacity 
to consent alone or should be enrolled with a caregiver. To aid in this decision 
regarding capacity, the treating clinician, who will be one of the study physicians, will 
consider the patient's MMSE/MoCA score, response to standard questionnaires, and 
clinical presentation. Consideration of capacity to make decisions and to understand 
treatment plans is an intrinsic aspect of routine clinical care at the Center.  
As in other memory disorders studies, if there is any doubt after detailed consideration 
of existing data and clinical judgment, clinicians will use the submitted “BHC Capacity 
Assessment” questionnaire to establish whether patients have a comprehensive 
understanding of the research being described. The study will follow the PHRC 
preferred order of surrogates when enrolling a patient with a caregiver. 

10 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
The study team will be readily available to answer questions and discuss more details 
in the subsequent, weekly encounters, and will have a low threshold for withdrawing 
subjects if there if is any concern for patient safety or unwillingness to participate. 
 
 
V. 
STUDY PROCEDURES 
 
Baseline, 6-month, and 12-month in-person study visits will start either at the Phyllis 
Jen Center for Primary Care (PJC), at Brigham and Women’s Hospital (BWH), at 45 
Francis Street, Boston, MA 02115, or at the Center for Brain/Mind Medicine (CBMM), 
located in the Neurosciences Center on the 1st Floor of the Building for Transformative 
Medicine (BTM). The building is located at 60 Fenwood Road in Boston, 
Massachusetts, 02115. Assessments will take place at the Clinical Trials Center or at 
the Clinical Trials Hub, at 45 Francis Street or 60 Fenwood Road respectively, both at 
the Center for Clinical Investigation, part of Brigham and Women’s Hospital (BWH).  
When in-person visits are not possible, baseline, 6-month, and 12-month visits will 
occur virtually on Enterprise Zoom, following MGB requirements for Zoom use.  
 
Procedures (for all participants): 
Visit 1 (Part 1) : All subjects will be administered a general cognitive screen 
(either an MMSE, or, MoCA), unless one has been completed within 1 month 
prior to Visit 1, and brief neuropsychological battery (PACC-BHC (Papp et al., 
2017); which includes: 1) Free and Cued Selective Reminding Test (FCSRT); 2) 
Logical Memory, immediate and delayed Story Recall; 3) Visual Paired 
Associates; 4) Digit-Symbol Substitution Test;  5) Trail Making Test, Part A; 6) 
Trail Making, Part B;  7) Number Span, 8) Category Fluency (animals, fruits, 
vegetables); and 9) Phonemic Fluency. (See tests, submitted). Caregivers, 
when determined necessary by the clinical team, will also be administered a 
Neuropsychiatric Inventory-Questionnaire (NPI-Q; Kaufer 2000) and Activities of 
Daily Living Questionnaire (ADLQ; Johnson 2004). All subjects will also 
complete: a demographic information questionnaire, a general survey querying 
their current cognitively/socially stimulating activities and experiences (a study-
specific tool, which also embeds the Florida Cognitive Activities Scale (FCAS) 
within; Schinka 2005), a physical activity survey (PASE; Washburn 1993), a 
sedentary behavior survey (SIT-Q-7d survey; Wijndale 2014), a questionnaire 
addressing current mood (Geriatric Depression Scale; Gilley 1997), a general 
sleep survey (Medical Outcomes Sleep-Study Scale; Hays 1992), a dietary 
intake questionnaire (Mediterranean Score; Goulet 2003), a survey which 
reveals social network size (Social Network Index; Cohen 1997) and degree of 
social connectedness (Social Connectedness and Social Assurance Scale; Lee 
1995), a survey that queries overall quality of life (Flanagan Quality of Life 

11 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
Scale; Burckhardt 2003), and a survey measuring level of self-activation (PAM-
13; Hibbard 2005). A questionnaire about observed changes in the subject’s 
memory and daily functioning will be completed by the participant, and 
separately by a study partner identified at the start of the study (“informant”) 
(CFI; Amariglio et al., 2015). Participants will have the option to complete 
questionnaires on paper or electronically via REDCap’s survey feature. If Visit 1 
is completed virtually, participants will be sent instructions for downloading the 
study mobile applications and setting up their Fitbit devices. 
 
Photographed dietary intake: Subjects will photograph all food and drink intake 
using the “Food Log” photo function on the Fruit Street application (for BHC 
participants) or MealLogger Pro (for PCE participants) for a consecutive, 4-day 
period, including one weekend day, within two weeks of each assessment 
(Baseline, 6-month, and 12-month visits). The photographs will be analyzed by 
the study dietician to compare to self-reported diet on Mediterranean Score 
questionnaire. Additional details about MealLogger Pro are in PCE arm 
procedures (below). 
Fitbit: All subjects will receive a Fitbit Inspire HR device, either at their in-person 
enrollment visit or by mail. Subjects will be instructed to wear the device for a 
consecutive, 4-day period, including one weekend day, within two weeks of each 
assessment (Baseline, 6-month, and 12-month visits). The data from the device, 
which is viewable by the team through the secure Fruit Street application, will be 
analyzed to compare to self-reported physical activity on the PASE questionnaire. 
Use of the Fitbit device between assessment periods will be encouraged but not 
required. 
The BHC program arm, procedures:  
Visit 1: (Part 2) Following consent and randomization by the clinician and the 
BHC, the team will review logistical details about the weekly encounters and 
monthly in-person or virtual visits with the BHC. Study personnel will introduce 
Fruit Street, a HIPAA-compliant mobile health application with video calling and 
two-way messaging feature, which has been well-established for diabetes 
prevention, and the Fitbit device and mobile application. Personnel will instruct 
subjects on how to download and navigate each of the applications, set up their 
Fitbit device, and sync the applications. Subjects will be assigned a deidentified 
username and password to log in to the applications. If participants do not own a 
smart phone, one will be provided by the study team for use during the study. 
Weekly 15-minute virtual interactions will occur within the Fruit Street 
application. The study team will establish preference for in-person or virtual 

12 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
visits (within the Fruit Street application) at 6, 12, and 18 weeks. In-person visits 
will be encouraged, but not required. The team will also establish 
subject/caregiver’s preference for use of either Gateway, email, or phone 
contact for study-related communications. If email is the preferred method of 
contact, study staff will determine the preference for send secure or unencrypted 
email, and unencrypted email consent will be obtained as necessary. 
Weekly encounters: 1, 2, 3, 4, 5 (Weeks 1-5): 15-minute motivational interview 
sessions between BHC, subject, and caregiver (if applicable). Content will 
include discussion of progress and challenges of meeting the personalized 
goals. The BHC will record/track progress and challenges toward goals in brief, 
clinical progress notes in the electronic medical record (EMR). Communication 
between the patient and the BHC will occur within Fruit Street, using either the 
website or the mobile application. Between weekly encounters, participants may 
communicate with the health coach regarding their progress, challenges, or 
questions via in-app messaging.  
Visit 2: (Week 6, +/- 1 week):  60-minute visit (in person or virtual). 
Part 1 (15 minutes) will involve subject, caregiver (if applicable) and 
BHC. The BHC will employ motivational interviewing and behavioral 
activation techniques to encourage healthy behaviors, review the last 5 
weeks of brain health activities, identify barriers to achieving goals, and 
prepare written/verbal short-term goals with subject in advance of Visit 3. 
Part 2 (45 minutes) will involve subject, BHC, caregiver (if applicable) 
and research dietician. The dietician will carry out individual nutritional 
counseling, which will involve:  Detailed Mediterranean diet nutrition 
education (see “Brain Health and Diet” supplement), a structured review 
of current dietary intake, and personalized recommendations to improve 
adherence to the Mediterranean diet.  
 
Weekly encounters: 6, 7, 8, 9, 10 (Weeks 7-11): 15-minute motivational 
interview sessions between BHC, subject, and caregiver (if applicable). Content 
will include discussion of progress and challenges of meeting the personalized 
goals. The BHC will record/track progress and challenges toward goals in brief, 
clinical progress notes in the electronic medical record (EMR). Between weekly 
encounters, participants may communicate with the health coach regarding their 
progress, challenges, or questions via in-app messaging. 
Visit 3: (Week 12, +/- 1 week) 30-minute visit (in person or virtual) to involve 
BHC, subject, and caregiver (if applicable). BHC will employ motivational 

13 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
interviewing concepts and style, review of last 5 weeks of brain health activities, 
identify barriers to achieving goals, and prepare written/verbal short-term goals 
with subject in advance of Visit 4. When appropriate, this visit may be combined 
with a standard neurology or primary care follow-up visit, which would involve 
physician education and counseling, including medication management, 
cognitive/neuropsychiatric assessment, and referral to other providers or social 
workers, if needed. 
Weekly encounters:  11, 12, 13, 14,15 (Weeks 13-17): 15-minute motivational 
interview sessions between BHC, subject, and caregiver (if applicable). Content 
will include discussion of progress and challenges of meeting the personalized 
goals. The BHC will record/track progress and challenges toward goals in brief, 
clinical progress notes in the electronic medical record (EMR). Between weekly 
encounters, participants may communicate with the health coach regarding their 
progress, challenges, or questions via in-app text messaging. 
Visit 4: (Week 18, +/- 1 week): 30-minute visit (in person or virtual) to involve 
Brain Health Champion, subject, and caregiver (if applicable).Champion will 
employ motivational interviewing concepts and style, review of last 5 weeks of 
brain health activities, identify barriers to achieving goals, and prepare 
written/verbal short-term goals with subject in advance of Visit 5. 
Weekly encounters:  16, 17, 18, 19, 20 (Weeks 19-23): 15-minute motivational 
interview sessions between BHC, subject, and caregiver (if applicable). Content 
will include discussion of progress and challenges of meeting the personalized 
goals. The BHC will record/track progress and challenges toward goals in brief, 
clinical progress notes in the electronic medical record (EMR). Between weekly 
encounters, participants may communicate with the health coach regarding their 
progress, challenges, or questions via in-app text messaging. 
Visit 5: End-of-Intervention (6-month assessment; Week 24 +/- 1 week).   
Part 1. 30-45 minutes. Routine primary care or neurology follow-up 
visit, involving subject, BHC, caregiver (if applicable) and treating 
provider. In this visit, the provider will address any current medical and 
health concerns and medication management, as per usual. BHCs will 
then provide a brief, overall assessment and summary of subjects’ 
progress in achieving personalized brain health goals, and whether they 
met the threshold for consensus-driven, brain health activity guidelines in 
the 6-month intervention. 
Part 2.  2 hours. End-of-Intervention assessment. Participants will 
complete all the assessments they completed at Visit 1/Part 1 (see 
above). In addition, they will complete general and health-coach/mobile 

14 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
health specific feedback on the intervention. Participants will then be 
asked through a different informed consent process, if they are willing to 
be randomized to a 6-month “booster” study extension vs. having no 
additional contact with the study team. 
Biweekly “booster” encounters (for subjects randomized to receive them): 
15-minute motivational interview sessions between BHC, subject, and caregiver 
(if applicable). Content will include assessing maintenance of brain health 
behavioral changes, identifying challenges to maintaining brain health changes, 
and brainstorming solutions to improve adherence to goals and 
recommendations.  
Visit 6: (1-year assessment [6-month post end-of-Intervention]); Weeks 50-
52):  2 hours. Subjects and study partners will complete all the assessments 
they completed at Visit 1/Part 1 (see above). 
Additional visits: If needed for any routine medical care, primary care visits will 
continue to occur during study enrollment, from baseline through Week 48. 
When possible, and as in the study design of a clinical team approach, BHCs 
will be present for these visits. After all medical concerns are addressed, BHCs 
will promote ongoing brain health behaviors for participants.  
The Physician counseling and education (PCE) arm, procedures:  
Visit 1: (Part 2) (Week 0) 15-20 minutes. Participating providers will review the 
essentials of brain-healthy behaviors, guided by an educational handout (“Brain 
Health Education Handout”) which will be given to subjects. Physicians will lead 
a discussion about specific ways to optimize brain healthy behaviors. Study 
personnel with also introduce the Fitbit device and mobile application and 
MealLogger Pro, a mobile application used for photographing food intake, and 
will instruct subjects on how to download and navigate the applications and set 
up their Fitbit device. Subjects will be assigned a deidentified username and 
password to log in to the MealLogger Pro and Fitbit applications. If participants 
do not own a smart phone, one will be provided by the study team for use 
during the study. The team will also establish subject/caregiver’s preference for 
use of either Gateway, email, or phone contact for study-related 
communications. If email is the preferred method of contact, study staff will 
determine the preference for send secure or unencrypted email, and 
unencrypted email consent will be obtained as necessary. 
Visit 2: (6-month assessment; Week 24 +/- 1 week) 2 hours, 20 min  
Part 1.  20 minutes. A neurology or primary care follow-up visit will occur at 
week 24, involving participant, caregiver (if applicable), and participating 

15 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
provider. In this visit, the provider will address current medical and health 
concerns and medication management, as per usual. Physicians will then 
review the essentials of brain healthy behaviors with subjects and discuss the 
status of subjects’ following through on brain health behavior recommendations 
introduced at Visit 1.  
Part 2.  2 hours. End-of-Intervention assessment.  Participants and study 
partners will complete all the assessments they completed at Visit 1/Part 1 (see 
above). In addition, they will complete general feedback on the intervention. 
Every 6 weeks between Visit 1 and Visit 2 (Weeks 6, 12, and 18), PCPs will 
distribute educational handouts summarizing recommendations via the 
electronic patient portal and on paper, in order to reinforce the material taught at 
Visit 1. 
Visit 3: (1-year assessment [6-month post end-of-Intervention]):  2 hours. 
Subjects and study partners will complete all the assessments they completed 
at Visit 1/Part 1 (see above).  
As is discussed in the informed consent form, all participants may be contacted 
1 year or more following the end-of-the study to for additional feedback and to 
complete additional questionnaires, if willing. 
Subjects’ basic demographic and health information, as well as the study team’s 
notes from all of the study encounters, will be recorded in an off-line, study 
database, which is protected by Partners Health Care IT security.  
 
 
VI. 
BIOSTATISTICAL ANALYSIS 
 
The study endpoint in this 6-month, open-label, randomized controlled trial is the 
absolute change or percent change of participants’ brain healthy activities, as 
measured by three questionnaires/scales: the Mediterranean Score, the PASE, and a 
survey on cognitively/socially stimulating activities and experiences (see Procedures, 
above, for references related to these instruments). 
 
We will mainly use multivariate analysis of covariance (MANCOVA) methods to 
compare the Brain Health Champion (BHC) program intervention to physician 
counseling and education (PCE). We will attempt to control for various background 
factors, such as the severity of cognitive deficits within each disease condition (i.e., 
there is a range of cognitive functioning for those included the diagnosis of Mild 
Cognitive Impairment), and variations in the delivery of care between different 
physicians. We will complete both an intention to treat (ITT) analysis including all 
subjects and a subanalysis including only subjects who finished (did not drop out) of 
the study. Secondary analysis will look at the correlations between self-report physical 
activity (PASE) and FitBit step counts, and self-report Mediterranean diet adherence 

16 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
and quatified/photographed dietary intake.  
 
In addition to the main analysis, we will also analyze changes from baseline in various 
measures for the two conditions, including: overall cognitive function (MMSE, MoCA), 
neuropsychiatric status (NPI-Q), dementia risk score (CAIDE), sleep behavior and 
quality of sleep (MOS-SS), daily functioning (ADLS), patient activation (PAM-13), 
sedentary behavior (SIT-Q-7d), Geriatric Depression Scale (GDS), and overall quality 
of life in neurologic patients (Flanagan QOL scale).  We will also perform separate 
analyses for closer investigation of how age and the involvement of a caregiver may 
modify the experimental effects. In the intervention (BHC) group, we will investigate the 
effect of monthly “booster” sessions on subjects’ maintenance of brain healthy changes 
after the 6-month intervention, compared to BHC subjects who receive no additional 
contact from the study team. 
 
A power analysis is not applicable here. This proof-of-concept, controlled pilot study 
will not have an adequate sample size to yield any reasonable degree of statistical 
power from the results. 
 
 
VII. 
RISKS AND DISCOMFORTS  
 
Physical Exercise 
 
This study is a clinical treatment program that includes the continued, weekly 
recommendations for subjects to carry out physical exercise. The type of aerobic, 
physical activity that is recommended, and that is beneficial for brain health, requires 
that subjects have some modicum level of cardio-pulmonary fitness. The treating 
clinician who is selecting possible subjects will screen for this level of fitness in the 
course of the initial neuro-medical evaluation of the subject, and the Brain Health 
Champion will regularly monitor subjects’ tolerance to the recommended physical 
exercise through the study course, with regular feedback to the clinician. Subjects or 
caregivers/partners who report that the exercise recommendations are too difficult or 
deleterious to health in any way will immediately be advised to reduce or cease their 
efforts.  
 
In order to screen for any medical or psychological concerns which would impede 
subjects’ study participation, either because of exercise intolerance or suspected 
intolerance to repeat cognitive testing, the treating clinician/investigator will also contact 
all subjects’ PCPs, prior to study commencement, by clinical messaging or telephone. 
 
 
Weekly Study Encounters 
 
A member of the study team (the BHC) will initiate weekly encounters with 
subjects/partners by video, telephone, or e-correspondence.  Subjects may become 
frustrated by this weekly contact. They will be encouraged from the start of the study to 
express concerns to the study team about their psychological well-being, in relationship 
to the frequency of this contact, through the course of the study. 

17 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
 
 
Repeated cognitive, functional, and neuropsychiatric testing 
 
This study requires subjects to complete various health questionnaires and perform 
basic cognitive and behavioral tasks at several time points throughout the course. 
Subjects may become anxious, tired, or frustrated with these tasks. The study team is 
well trained in the administration of these instruments and will attempt to make subjects 
as comfortable as possible. Subjects and partners can take a break or discontinue the 
testing at any time.   
 
Fruit Street Security 
 
Fruit Street has implemented reasonable measures to protect the information that they 
collect and store (e.g. hashed user password and SSL encryption), taking into 
consideration the types of risks they face and the reasonable protections available to 
them. No method of protecting information is 100% secure, and they cannot guarantee 
its absolute security. Consequently, they cannot ensure or warrant the security of any 
information that participants transmit to them. Once Fruit Street receives participant 
data, they take steps to ensure security on their systems and/or on the systems of their 
service providers, but this is not a guarantee that such information may not be 
accessed, disclosed, altered, or destroyed by breach of such safeguards. 
 
 
VIII.    Potential Benefits 
 
Study participants will have the chance to personally benefit from increased adherence 
to current, evidence-based recommendations for brain healthy behaviors. However, 
there are no proven health benefits to participating in this study. 
 
Study participants and their caregivers/partners will have the chance to personally 
benefit from increased adherence to current, evidence-based recommendations for 
brain healthy behaviors. However, there are no proven benefits to participating in this 
study.  
 
More globally, the results of this study will inform the current, clinical treatment of 
patients with subjective cognitive complaints and with cognitive disorders at the BWH 
Alzheimer Center.    
 
All participants can receive up to $300 compensation for participating in the study. 
Compensation will be split into three installments of $100, paid after the baseline 
assessment (0 months), end-of-intervention assessment (6 months), and end-of-study 
assessment (12 months). If participants are compliant with wearing their Fitbit device, 
they will get to keep it at the end of the study. If participants are not compliant, a pre-
paid envelope will be mailed to their house so that they can return the device free of 
cost. In certain circumstances, when providing one’s own transportation is a barrier to 
participation, study funds will cover the cost of transportation to in-person study visits. 

18 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
Additionally, parking passes will be provided for all in-person study visits.  
 
 
IX. 
MONITORING AND QUALITY ASSURANCE 
 
The Principal Investigator will report any and all serious and non-serious adverse 
events to the Partners IRB within a timely manner.  Study personnel must immediately 
report to the PI any adverse events from this study. All adverse events will be reviewed 
by the PI and reported to the Partners Human Research Committee (HRC) in 
accordance with ICH Guidelines. The PI will maintain a tracking log to reflect all 
adverse events regardless of relationship or expectedness and submit the updated log 
each year during the IRB renewal process. 
 
The PI will be responsible for monitoring and assuring the validity and integrity of all of 
the data, for monitoring the day-to-day activities of all study procedures, and for the 
adherence to the IRB-approved protocol.  
 
 
 
X. 
REFERENCES 
 
 
Amariglio RE, Donohue MC, Marshall GA, et al. Tracking early decline in cognitive 
function in older individuals at risk for Alzheimer disease dementia: the Alzheimer's 
Disease Cooperative Study Cognitive Function Instrument. JAMA Neurol 
2015;72(4):446-54 doi: 10.1001/jamaneurol.2014.3375. 
 
Beckett MW, Ardern CI, Rotondi MA. A meta-analysis of prospective studies on 
the role of physical activity and the prevention of Alzheimer's disease in older adults. 
BMC Geriatr. 2015 Feb 11;15:9. doi: 10.1186/s12877-015-0007-2. PubMed PMID: 
25887627. 
 
Burckhardt, C. S., Anderson, K. L., Archenholtz, B., & Hagg, O. (2003). The Flanagan 
Quality of Life Scale: Evidence of construct validity. Health and Quality of Life 
Outcomes, 1, 59. doi: 10.1186/1477-7525-1-59 
 
Cohen S, Doyle WJ, Skoner DP, Rabin BS, Gwaltney JM Jr. Social ties and 
susceptibility to the common cold. JAMA. 1997 Jun 25;277(24):1940-4. PubMed PMID: 
920063 
 
Dal Bello-Haas VP, O'Connell ME, Morgan DG, Crossley M. Lessons learned: 
feasibility and acceptability of a telehealth-delivered exercise intervention for 
rural-dwelling individuals with dementia and their caregivers. Rural Remote 
Health. 2014;14(3):2715. PubMed PMID: 25081991 
 
Dannhauser TM, Cleverley M, Whitfield TJ, Fletcher BC, Stevens T, Walker Z. A  
complex multimodal activity intervention to reduce the risk of dementia in mild cognitive 
impairment--ThinkingFit: pilot and feasibility study for a randomized controlled trial. 

19 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
BMC Psychiatry. 2014 May 5;14:129. doi: 10.1186/1471-244X-14-129. PubMed PMID: 
24886353 
 
Gilley DW, Wilson RS. Criterion-related validity of the Geriatric Depression 
Scale in Alzheimer's disease. J Clin Exp Neuropsychol. 1997 Aug;19(4):489-99. 
PubMed PMID: 9342685 
 
 
Goode AD, Reeves MM, Eakin EG. Telephone-delivered interventions for physical  
activity and dietary behavior change: an updated systematic review. Am J Prev 
Med. 2012 Jan;42(1):81-8. doi: 10.1016/j.amepre.2011.08.025. Review. PubMed 
PMID: 22176852. 
 
Hays, R. D., & Stewart, A. L. (1992). Sleep measures. In A. L. Stewart & J. E. Ware 
(eds.), Measuring functioning and well-being: The Medical Outcomes Study approach 
(pp. 235-259), Durham, NC: Duke University Press. 
 
Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R,  
Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon 
DM; ERICCA Trial Investigators.. Remote Ischemic Preconditioning and Outcomes of  
Cardiac Surgery. N Engl J Med. 2015 Oct 8;373(15):1408-17. doi: 
10.1056/NEJMoa1413534. PMID: 26436207 
 
Hibbard JH, Mahoney ER, Stockard J, Tusler M. Development and testing of a 
short form of the patient activation measure. Health Serv Res. 2005 Dec;40(6 Pt 
1):1918-30. PMID: 16336556 
 
Johnson N, Barion A, Rademaker A, Rehkemper G, Weintraub S. The Activities of  
Daily Living Questionnaire: a validation study in patients with dementia. 
Alzheimer Dis Assoc Disord. 2004 Oct-Dec;18(4):223-30. PMID: 15592135 
 
Kaufer DI, Cummings JL, Ketchel P, Smith V, MacMillan A, Shelley T, Lopez OL,  
DeKosky ST. Validation of the NPI-Q, a brief clinical form of the 
Neuropsychiatric Inventory. J Neuropsychiatry Clin Neurosci. 2000 
Spring;12(2):233-9. PubMed PMID: 11001602 
 
Lee R.M., and Robbins S.B. 1995. Measuring Belongingness: The Social 
Connectedness and the Social Assurance Scales. Journal of Counseling Psychology. 
1995. Vol. 42. No. 2. 232-241   
 
Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, 
exercise, cognitive training, and vascular risk monitoring versus control to prevent 
cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. 
Lancet 2015;385(9984):2255-63 doi: 10.1016/S0140-6736(15)60461-5. 
 
Okereke OI, Rosner BA, Kim DH, et al. Dietary fat types and 4-year cognitive change 
in community-dwelling older women. Ann. Neurol. 2012;72(1):124-34 doi: 
10.1002/ana.23593. 
 

20 
 
Detailed Protocol – The Brain Health Champion Study - V 11.0, 6/12/20 
 
Papp KV, Rentz DM, Orlovsky I, Sperling RA, Mormino EC. Optimizing the preclinical 
Alzheimer's cognitive composite with semantic processing: The PACC5. Alzheimers 
Dement (NY) 2017;3(4):668-77 doi:10.1016/j.trci.2017.10.004. 
 
Schinka JA, McBride A, Vanderploeg RD, Tennyson K, Borenstein AR, Mortimer JA. 
Florida Cognitive Activities Scale: initial development and validation. J Int 
Neuropsychol Soc. 2005;11(1):108-116. 
 
Smith JC, Lancaster MA, Nielson KA, Woodard JL, Seidenberg M, Durgerian S, 
Sakaie K, Rao SM. Interactive effects of physical activity and APOE-ε4 on white matter 
tract diffusivity in healthy elders. Neuroimage. 2016 May 1;131:102-12. doi: 
10.1016/j.neuroimage.2015.08.007. PubMed PMID: 26265157;  
 
Sobol NA, Hoffmann K, Frederiksen KS, Vogel A, Vestergaard K, Brændgaard H, 
Gottrup H, Lolk A, Wermuth L, Jakobsen S, Laugesen L, Gergelyffy R, Høgh P, 
Bjerregaard E, Siersma V, Andersen BB, Johannsen P, Waldemar G, Hasselbalch SG, 
Beyer N. Effect of aerobic exercise on physical performance in patients with 
Alzheimer's disease. Alzheimers Dement. 2016 Dec;12(12):1207-1215. doi: 
10.1016/j.jalz.2016.05.004. PubMed PMID: 27344641. 
 
Vleet TV, DeGutis J, Dabit S, Chiu C. Randomized control trial of 
computer-based rehabilitation of spatial neglect syndrome: the RESPONSE trial 
protocol. BMC Neurol. 2014 Feb 7;14:25. doi: 10.1186/1471-2377-14-25. PubMed 
PMID: 24502769; PubMed Central PMCID: PMC3922254. 
 
Washburn RA, Smith KW, Jette AM, Janney CA. The Physical Activity Scale for the 
Elderly (PASE): development and evaluation. J. Clin. Epidemiol. 1993;46(2):153-62. 
 
Wijndale K, De Bourdeaudhuij I, Godino JG, Lynch BM, Griffin SJ, Westgate K, Brage 
S. Reliability and validity of a domain-specific last 7-d sedentary time 
questionnaire. Med Sci Sports Exerc. 2014;46:1248–1260. 
 
Wilson RS, Mendes De Leon CF, Barnes LL, et al. Participation in cognitively 
stimulating activities and risk of incident Alzheimer disease. JAMA 2002;287(6):742-8. 
 
 
 
 
BWH/MGH Human Subjects Research Application Form 
Filename: Detailed Protocol 
Version 4: March 2002 
Page 1