Gamification to Improve Physical Activity in Older Adults at Risk for Alzheimer's: the STEP 4Life Trial
Phase: NA
Conditions: Alzheimer Disease, At Risk, Alzheimer Disease, Protection Against, Dementia
Sponsor: University of Pennsylvania

Gamification to Improve Physical Activity in Older Adults: 
the STEP 4Life Trial  
 
Study Protocol 
 
June 3, 2021 
 
 
 

  
 
Outline 
1. Abstract 
2. Overall objectives 
3. Aims 
 
3.1 Primary outcome 
 
3.2 Secondary outcomes 
4. Background 
5. Study design 
 
5.1 Design 
 
5.2 Study duration 
 
5.3 Target population 
 
5.4 Accrual 
 
5.5 Key inclusion criteria 
 
5.6 Key exclusion criteria 
6. Subject recruitment 
 
6.1 General 
 
6.2 Populations vulnerable to undue influence or coercion  
7. Subject compensation 
8. Study procedures 
 
8.1 Consent 
 
8.2 Procedures 
 
8.3 Instruments 
9. Analysis plan 

10. Investigators 
11. Human research protection 
 
11.1 Data confidentiality 
 
11.2 Data management 
 
11.3 Subject confidentiality 
 
11.4 Subject privacy 
 
11.5 Data disclosure 
 
11.6 Data safety and monitoring 
 
11.7 Risk/benefit  
 
 
11.7.1 Potential study risks 
 
 
11.7.2 Potential study benefits 
 
 
11.7.3 Risk/benefit assessment 
 
 
11.7.4 Alternatives to participation 
 
11.8 Resources necessary for human subjects protections 
 
1. Abstract 
Increased physical activity by walking further or more vigorously may prevent or delay the 
development of Alzheimer’s Disease and Related Dementias (ADRD) but reaching higher levels 
of activity and maintaining it as a long-term habit is difficult to do. This project will use concepts 
from behavioral science to create a game older adults can play in order to increase their levels of 
activity while having fun doing it. The game is played with a support partner who is a spouse, 
family member, or close friend who provides feedback and encouragement to help the game-
player reach activity goals and maintain them as habits over time. Participants in the game will 
use their own smartphone and a wristwatch that tracks activity (such as a FitBit, provided by this 
study) to set goals, get feedback, and play the game for 12 weeks. Participants will be asked to 
continue wearing the wristwatch for another 6 weeks to track activity after the game is over. To 
determine the effectiveness of this game, we will randomly assign 50 people to the game and 50 
people to only get the wristwatch but no game component. All participants in this study will be 
recruited from an online registry of adults age 55-75 who have not been diagnosed with 
Alzheimer’s (GeneMatch) which offers genetic testing on risk for ADRD to all participants. We 

will recruit participants to our study who have elevated genetic risk as well as those without 
specific genetic risks to see if either group responds differently to the game. 
2. Overall objectives 
The primary objective is to assess the effectiveness of a social incentive-based gamification 
intervention to increase physical activity over 12 weeks with follow up of 6 weeks after the 
intervention concludes. We will explore whether participants who know they are higher risk 
(carriers of the APOE4 gene) are more responsive to the intervention than those who know they 
are at average risk (non-carriers of APOE4). We will also explore the feasibility of collecting 
measures of cognition and function remotely using standardized instruments by telephone or 
video calls. 
3. Aims 
3.1 Primary outcome: change in mean daily step count from the baseline period to the 
end of the 12-week intervention period. 
3.2 Secondary outcome: mean daily step count during the 6-week follow up period after 
the end of the intervention. 
3.3 Exploratory outcomes: functional measures will include the Timed Up and Go and 
30-second Chair Stand Test.45,46 Cognitive measures will include Verbal Naming, 
Category Fluency, Trail Making, Number Span, and Blind MOCA.47  
 
4. Background 
Systematic reviews have demonstrated that higher levels of physical activity are associated with 
lower risk of developing ADRD even with modest increases in low-intensity exercises.1-3 
Physical Activity Guidelines from the U.S. Department of Health and Human Services also 
recommend ≥150 minutes/week of moderate intensity physical activity (e.g., brisk walking) for 
older adults to reduce risks of functional and cognitive decline (including ADRD specifically).4,5  
Physical activity is also recommended by the NIA for people with ADRD and taking daily walks 
with a support partner is specifically encouraged.6 Some studies have suggested higher intensity 
exercise or multi-component interventions may have the greatest impact but the sustainability 
and scalability of these approaches are major limitations. 
Interventions leveraging behavioral economics (BE) to increase physical activity have 
demonstrated sustainability over prolonged periods after the end of the intervention;7 however, 
these approaches have not been applied to populations at risk for ADRD specifically. There are 
several key components of these interventions which warrant testing in this population. First, 
gamification leverages BE concepts to motivate behavior change. Gamification is the use of 
game-design elements such as points and levels in non-game contexts.9,10 Gamification is an 

appealing approach to increase engagement in healthy behaviors because it makes the “hard 
stuff” fun by turning obligations into goals and challenges.10 Second, mobile technologies which 
increasingly used by older adults11 can be used to accurately,12 and unobtrusively help set and 
maintain specific daily and weekly activity goals. Third, social incentives can be used to enhance 
these effects and reinforce habit formation to prevent regression. Social incentives are powerful 
influences that motivate individuals to change their behaviors based on social ties or 
connections.14-17 For example, an individual’s mobility is higher when a family member or friend 
has increased mobility.17 On closer inspection, such interactions contain many powerful levers to 
change human behavior including peer support, accountability, and collaboration. Since social 
networks are ubiquitous, approaches that harness social incentives could be scaled more broadly 
at lower cost than interventions relying on health care professionals to motivate and monitor 
physical activity in older adults at risk for ADRD. Our group has successfully used gamification, 
mobile technologies, and social incentives to increase activity in several non-ADRD populations. 
One challenge to studying behavioral interventions to improve physical activity in the ADRD 
population has been enrollment with most studies to date enrolling from clinics which limits 
sampling; prior studies have also used variable definitions of “elevated risk” for dementia. In this 
study, we identify and recruit participants utilizing a novel, national cohort of individuals with 
quantifiable risk using genetic testing from the GeneMatch study.18,19  
5. Study design 
 
5.1 Design 
We will conduct a 2-arm, randomized, controlled trial over 12 weeks with 6 weeks of follow-up 
(18 weeks total) that compares a control group that uses a wearable device to track physical 
activity to an intervention group that uses the same wearable devices and receives a supportive 
social incentive-based gamification intervention to adhere to a step goal program. In phase 1 (2 
weeks), participant step counts will be monitored and baseline step count will be estimated. In 
phase 2 (12 weeks), participants will be randomly assigned to the control or intervention group 
and will set step count goals. In phase 3 (6 weeks), interventions will cease and participant step 
counts will be monitored. Participants will be considered enrolled in the trial if they complete the 
run-in period and then are randomized.  
 
5.2 Study duration 
The study will begin in Summer 2021.  The primary intervention period is 12 weeks. Participants 
will be enrolled for approximately 20 weeks (2 week run-in, 12 week intervention, 6 week 
follow up). We expect the entire study to take approximately one year to conduct and analyze 
outcomes. 
 
5.3 Target population 
Adults age 55-75, own a smartphone, enrolled in GeneMatch, know their genetic testing results 
(APOE4), and able to provide informed consent 
 

5.4 Accrual 
We will aim to enroll and randomize 100 participants. We estimate a standard deviation of 2500 
steps and a sample of 100 participants allocated in a 1:1 distribution (50 in each arm), will ensure 
at least 80% power to detect a 1000 step difference.  This calculation assumes a 10% dropout 
rate and a conservative Bonferroni adjustment of the type I error rate with a 2-sided alpha of 
0.017. 
 
5.5 Key inclusion criteria 
Participants must be age 55-75, own a smartphone, be enrolled in GeneMatch, know their 
genetic testing results (APOE4), and able to provide informed consent 
 
5.6 Key exclusion criteria 
1) Inability to provide informed consent; 2) does not have daily access to a smartphone 
compatible with the wearable device and not willing to use a device that we can provide them; 3) 
already enrolled in another physical activity study; 4) unable to ambulate independently; 5) any 
other medical conditions that would prohibit participation in physical activity program;  
6. Subject recruitment 
6.1 General 
Participants will be recruited from the Alzheimer Prevention Initiative’s (API) GeneMatch 
registry, which is managed by the Banner Alzheimer’s Institute. GeneMatch maintains a registry 
of older adults who live in the United States and do not have a diagnosis of cognitive 
impairment. GeneMatch will identify potential participants based on age (55-75). GeneMatch 
will invite these individuals through an email invitation and a study description on their 
GeneMatch dashboard. Potential participants will have the option to accept or decline the study 
invitation. If participants accept, they acknowledge that their information will be shared with the 
study team and that a member of the study team will contact them. Those who decline the 
invitation will not be contacted again, and none of their information will be shared with the study 
team. Study coordinators will contact potential participants who accept the invitation via 
phone/email to further assess interest and answer questions related to the study. 
 
6.2 Populations vulnerable to undue influence or coercion 
Not applicable 
7. Subject compensation 
Participants will receive $100 on a pre-paid debit card (Clincard) upon completion of the study.  
8. Study procedures 

 
8.1 Consent 
Upon recruitment, potentially interested participants will be directed to the Way to Health 
internet research portal. Upon reaching the portal, eligibility will be determined based on their 
responses to screening questions. 
The Way to Health portal will take eligible potential participants through an automated online 
informed consent session. The consent session will be divided into sections and potential 
participants will have to click a button to advance through each section. This is to help ensure 
that participants read the consent form thoroughly by breaking down the form into more 
manageable blocks of text. Successive screens will explain the voluntary nature of the study, the 
risks and benefits of participation, alternatives to participation, and that participants can cease to 
participate in the study at any time. 
On the final consent screen, potential participants who click a clearly delineated button stating 
that they agree to participate in the study will be considered to have consented to enroll. 
Following consent and the run-in period, the participant will be randomized to intervention or 
control arm by the web application. The participant will see a description of the details specific 
to that arm. Participants will be provided with details regarding how to contact the research team 
via email or phone at any time if they wish to withdraw from the study subsequently or have any 
questions or concerns about participation. Such contact information will remain present via the 
subjects Way to Health individual study website dashboard throughout the study. Participants 
will also be able to access a PDF of the consent form through the study Way to Health site.  
 
Waiver or Alteration of Informed Consent* 
Are you requesting a waiver of, or alteration to, the informed consent process? Please choose one 
of the following and provide justification where appropriate: 
 
No Waiver Requested  
Waiver or alteration of required elements of consent  
Waiver of written documentation of informed consent: the only record linking the subject and the 
research would be the consent document and the principal risk would be potential harm resulting 
from a breach of confidentiality.  
X Waiver of written documentation of informed consent: the research presents no more than 
minimal risk of harm to subjects and involves no procedures for which written consent is 
normally required outside of the research context  
  
Written Statement of Research* 
Will subjects be provided a written statement of the research? 
 
X  Yes  
No 
 
8.2 Procedures 

Enrollment. Potential participants will complete a screening questionnaire through the Way to 
Health portal. If the participant successfully passes the screening questions, they can be 
consented to the study. After screening and consent, participants will complete a survey through 
the way to health platform to provide demographic information (Age, gender, race, ethnicity, 
income, education, self-report comorbidities/health conditions) as well as a shipping address for 
the Fitbit to be sent to. Participants will then receive a Fitbit activity tracker and instructions for 
setting up the tracker and the Fitbit app on their smartphone. After participants have successfully 
set up their activity tracker and app, and have linked their Fitbit account to the Way to Health 
website, they will begin the study run-in period. 
Run-In Period. Eligible participants will be mailed a wearable activity tracker that captures data 
on daily steps counts and asked to use the device for two weeks to get accustomed to it.  During 
this period, we will use a protocol from prior work to estimate a baseline step count using the 
second week of data. The first week of data will be ignored to diminish the tendency for use of 
devices in week 1 of receiving a new device to be significantly higher than what might be 
observed at steady state. To prevent risk of mismeasurement, we will ignore any daily values less 
than 1000 steps because evidence indicates these values are unlikely to represent capture of 
actual activity. Once baseline is established, participants will be contacted to conduct goal 
selection with a step goal of increase of 33%, 40%, 50% or choose a custom goal as long as it is 
at least 1500 steps greater than baseline. In prior work, we find that on average participants chose 
ambitious goals and more than half selected a 50% step increase. 
Participants with an average of 7500 or greater steps per day during days 8 - 14 of run-in will be 
ineligible and will not be randomized into the study. 
Randomization. After establishing baseline, participants will be randomly assigned to control or 
interventions using a 1:1 allocation and stratifying on baseline step count (< 4000, 4000-7000 
steps, >7000 steps) using an electronic number generator through the WTH platform. All 
participants will be asked to use the wearable device during the day and at night to measure 
activity. Each participant will select whether he or she would like to primarily receive study 
communications by text message, e-mail, or automated interactive voice response phone call. 
Cognition and Function Measures. Within 2 weeks of randomization (study weeks 2-4) and 
within 2 weeks after completing the intervention period (study weeks 15-16), participants will 
complete online survey-based assessments and virtual (video call) assessments of function 
(Timed Up and Go and 30-second Chair Stand) and cognition (Verbal Naming; Category 
Fluency; Trail Making; Number Span; Blind MOCA). The online surveys will be completed 
through the Way to Health online platform. Research staff will contact participants to schedule 
and conduct video calls to complete the tests of function and cognition.  
Intervention Period.  

Control: Participants in the control arm will receive a study device (e.g. FitBit) but no other 
interventions during the intervention or follow-up periods.  
Intervention: Intervention participants will enter a game designed with behavioral economics 
(BE) concepts to address predictable barriers to behavior change during the 12-week intervention 
period. The components of the gamification intervention are described below:  
Pre-commitment: Each participant signs a contract agreeing to try their best to achieve their daily 
step goal. Pre-commitment helps to motivate behavior change by increasing perceived 
accountability.18,19 Points: Each week, participants are endowed 70 points (10/day) prospectively 
rather than awarded after goal achievement to leverage the BE concept loss aversion that 
individuals are more motivated by immediate losses than gains.20-22  Each day that the goal is not 
met, they are informed that they lost 10 points. Points are replenished at the start of the week to 
leverage the BE concept of the “fresh start effect” that individuals are more motivated for 
aspirational behavior around temporal landmarks such as the start of the week.50 Levels: At the 
end of the week, if the participant has 40 points or more, he or she will advance one level.  The 
levels include: blue (lowest), bronze, silver, gold, platinum (highest). If they have < 40 points, 
they drop down one level. This creates a sense of achievable goals (goal gradients)23 and 
anticipated regret.24-27 Each participant begins in the middle (silver), so higher levels seem within 
reach and they will feel a sense of loss from dropping down a level. Support partner:  Each 
participant will select a spouse, family member, or friend that they see often to serve as a sponsor 
and receive a weekly email participant’s progress including points, game level, and average step 
count. This supportive sponsor will help to enhance social incentives to motivate the individual 
towards his or her goal.13  
Follow-Up Period. At the end of the 12 week Intervention Period participants will enter a 6 week 
Follow-Up Period during which interventions will cease but passive data collection of step 
counts will continue.  
Exit Survey. Participants will complete an end-of-study questionnaire on their experience with 
the wearable device and intervention design. Participants will be asked to describe elements that 
helped them to achieve their physical activity goals (and elements that did not help) and 
suggestions on how to improve the design of the interventions.  
Upon completion of the study, participants will receive payment of $100 on a pre-paid debit card 
(Clincard).  
8.3 Instruments 
Step Count: Daily step count data will be uploaded daily from participants' activity trackers.  
Screening Survey: A screening survey will be administered through the study website prior to 
enrollment to assess eligibility for the study. The survey will query age, use of smart phone, 
current activity level, participation in other research, ability to safely increase physical activity, 
availability of study partner, and knowledge of APOE genotype. 

Baseline/demographics: After consent and confirmation of eligibility, participants will complete 
a survey through the way to health platform to provide demographic information (Age, gender, 
race, ethnicity, income, education, self-report comorbidities/health conditions) as well as a 
shipping address for the Fitbit to be sent to.  
Cognition and Function: During the first two weeks of the intervention period and the first two 
weeks of the follow up period, participants will complete virtual (video call) assessments of 
function (Timed Up and Go and 30-second Chair Stand) and cognition (Verbal Naming; 
Category Fluency; Trail Making; Number Span; Blind MOCA). Research staff will contact 
participants to schedule and conduct video calls to complete the tests of function and cognition. 
Exit survey: Participants will complete an end-of-study questionnaire on their experience with 
the wearable device and intervention design. Participants will be asked to describe elements that 
helped them to achieve their physical activity goals (and elements that did not help) and 
suggestions on how to improve the design of the interventions. 
9. Analysis plan 
Similar to our prior work,22,44,54 the primary analysis will fit mixed effect regression models to 
evaluate changes in physical activity (steps per day and minutes of MVPA) adjusting for each 
participant’s baseline measure, time using calendar month fixed effects, participant random 
effects, and accounting for repeated measures. Secondary analyses will fit a fully adjusted model 
including other variables of interest such as participant demographic characteristics and 
comorbidities. We will also conduct a-priori exploratory subgroup analyses for participants with 
elevated risk (APOE4 carriers) and higher levels of social support on 1o and 2o outcomes. For 
these outcomes, we estimate a standard deviation of 2500 steps and a sample of 100 participants 
allocated in a 1:1 distribution (50 in each arm), will ensure at least 80% power to detect a 1000 
step difference.  This calculation assumes a 10% dropout rate and a conservative Bonferroni 
adjustment of the type I error rate with a 2-sided alpha of 0.017. 
In exploratory analyses, we will compare results from virtual functional and cognitive tests at the 
beginning of the study (after randomization) with results during the follow up period (after 
intervention ends). We do not anticipate major changes in these measures and are not powered to 
detect minor changes – these are feasibility measures to demonstrate we can conduct virtual 
performance tests at multiple intervals only. 
We will also conduct exploratory subgroup analyses of factors that may influence our primary 
outcome (change in mean steps/day) such as participant-reported social support and 
neighborhood walkability as determined by address/zipcode. These are factors that have been 
associated with steps in our prior work but this pilot will not adequately powered to detect 
statistical significance (we will explore for trends only). 
10. Investigators 

Ryan Greysen, MD, MHS, MA is the Principal Investigator (PI). He is the Director of Penn 
Center for Evidence-based Practice; his research focuses on outcomes of hospitalization for 
older, vulnerable adults during transitions of care and mobile technologies to engage this 
population.  
Jason Karlawish, MD is Co-Director of the Penn Memory Center and Director of the Penn 
Program on Precision Medicine for the Brain (P3MB). His research focuses on quality of life and 
ethical issues of disclosure of gene and biomarkers of Alzheimer’s disease risk in older adults. 
11. Human research protection 
 
11.1 Data confidentiality 
Paper-based records will be kept in a secure location and only be accessible to personnel 
involved in the study. Computer-based files will only be made available to personnel involved in 
the study through the use of access privileges and passwords. Wherever feasible, identifiers will 
be removed from study-related information. Precautions are in place to ensure the data are secure 
by using passwords and encryption, because the research involves web-based surveys. 
 
11.2. Data Management 
The Way to Health web platform will serve as the core mechanism for recruiting and enrolling 
subjects, transmitting general and intervention-specific messages, collecting activity tracker and 
online survey data, and providing regular feedback to subjects on their progress in the study.    
The Penn Medicine Academic Computing Services (PMACS) will be the hub for the hardware 
and database infrastructure that will support the project and is where the Way to Health web 
portal is based. The PMACS is a joint effort of the University of Pennsylvania's Abramson 
Cancer Center, the Cardiovascular Institute, the Department of Pathology, and the Leonard Davis 
Institute. The PMACS provides a secure computing environment for a large volume of highly 
sensitive data, including clinical, genetic, socioeconomic, and financial information. Among the 
IT projects currently managed by PMACS are: (1) the capture and organization of complex, 
longitudinal clinical data via web and clinical applications portals from cancer patients enrolled 
in clinical trials; (2) the integration of genetic array databases and clinical data obtained from 
patients with cardiovascular disease; (3) computational biology and cytometry database 
management and analyses; (4) economic and health policy research using Medicare claims from 
over 40 million Medicare beneficiaries. PMACS requires all users of data or applications on 
PMACS servers to complete a PMACS-hosted cybersecurity awareness course annually, which 
stresses federal data security policies under data use agreements with the university. The 
curriculum includes Health Insurance Portability and Accountability Act (HIPAA) training and 
covers secure data transfer, passwords, computer security habits and knowledge of what 
constitutes misuse or inappropriate use of the server. We will implement multiple, redundant 
protective measures to guarantee the privacy and security of the participant data. All 

investigators and research staff with direct access to the identifiable data will be required to 
undergo annual responsible conduct of research, cybersecurity, and HIPAA certification in 
accordance with University of Pennsylvania regulations.  
Data will be entered into the database through several different mechanisms.  Participants will 
enter their own personal information and respond to surveys through a PHP-based web interface.  
Activity tracker data will be transmitted from the activity tracker company to the study server 
through a secure connection. Researchers will have a separate interface that will allow them to 
manually enter data if needed. For example, to enter data from virtual cognitive and functional 
tests, researchers will login to Way to Health and complete evaluation forms based on 
attachments for Timed Up and Go (TUG), 30-second Chair Stand Test (30s CST), Verbal 
Naming, Category Fluency, Trail Making, Number Span, and Blind MOCA. 
Wherever possible, data will be de-identified for analysis. Personal information and research data 
will be stored in separate SQL tables and will be linked by a computer-generated ID number.   
It is unlikely that anyone will need to make corrections to the data, as most of the information is 
submitted by participants. Furthermore, the web platform will be set up with pre-specified ranges 
of eligible values for each question to minimize data entry errors. Specifically designated 
administrators will have the ability to make corrections, however each modification will be 
logged along with justification for the change. The original data will be preserved in a separate 
non-modifiable database. 
11.3 Subject confidentiality 
Research material will be obtained from participant surveys, assessments and from the wearable 
devices.  All participants will provide informed consent for access to these materials. The data to 
be collected include demographic data (e.g., age, sex, self-identified race), outcome data, and 
daily activity data collected by the wearable device.  Research material that is obtained will be 
used for research purposes only. The same procedure used for the analysis of automated data 
sources to ensure protection of patient information will be used for the survey data, in that 
identifiers will be used only for linkage purposes or to contact participants. The study 
identification number will be used on all data collection instruments. All study staff will be 
reminded to appreciate the confidential nature of the data collected and contained in these 
databases.  
Data will be stored, managed, and analyzed on a secure, encrypted server behind the University 
of Pennsylvania Health System (UPHS) firewall. All study personnel that will use this data are 
listed on the IRB application and have completed training in HIPAA standards and the CITI 
human subjects research. Data access will be password protected. Whenever possible, data will 
be de-identified for analysis. 
 
11.4 Subject privacy 

Potential participants will have the option to accept or decline the study invitation. If participants 
accept, they acknowledge that their information will be shared with the study team and that a 
member of the study team will contact them. Those who decline the invitation will not be 
contacted again, and none of their information will be shared with the study team. Enrollment 
will include a description of the voluntary nature of participation, the study procedures, risks and 
potential benefits in detail. Potential participants will have the opportunity to ask questions and 
review the consent form information with family prior to making a decision to participate. 
Participants will be told that they do not have to answer any questions if they do not wish and 
can drop out of the study at any time. They will be told that they may or may not benefit directly 
from the study and that all information will be kept strictly confidential, except as required by 
law. All efforts will be made by study staff to ensure subject privacy. 
 
11.5 Data disclosure 
The following entities, besides the members of the research team, may receive data for this 
research study: -Fitbit, the company that designs and manufactures the wearable devices used in 
the study to track participant physical activity. RedCap, a secure web application where 
participants’ informed consent forms will be stored. -Twilio, Inc., the company which processes 
some study-related messages. Twilio will store patients' phone numbers on their secure 
computers. -Qualtrics, Inc., the company which processes most study-related surveys. Qualtrics 
will house de-identified answers to these surveys on their secure servers. -The Office of Human 
Research Protections at the University of Pennsylvania -Federal and state agencies (for example, 
the Department of Health and Human Services, the National Institutes of Health, and/or the 
Office for Human Research Protections), or other domestic or foreign government bodies if 
required by law and/or necessary for oversight purposes. 
 
11.6 Data safety and monitoring 
At the time of enrollment, all patients will be given anticipatory guidance on when to seek 
medical attention (e.g. when to call their doctor should they feel dizzy, short of breath, chest 
pain, lightheaded, unstable, or otherwise unwell while ambulating).  In addition, participants will 
be asked to report to the study team any episodes of these symptoms that occur during 
ambulation to research staff.  Participants will also be reminded that they can always contact the 
study team by phone or email at any time (contact information will be given at the beginning of 
the study and will also be posted on the Way to Health platform, which can be accessed at any 
time by the participant).  If any concerns of a participant event are identified, the study 
coordinator will reach out to the participant and complete the event reporting form. This form 
will be reviewed with the study PI to determine if any action is needed and if the participant can 
continue safely in the study. Any identified adverse events will be reported to the Institutional 
Review Board.   

A Safety Officer will also be appointed to review IRB protocol and will review adverse events 
when enrollment is halfway complete. All adverse events that are serious or unexpected (i.e., 
have not been previously reported for the study's intervention) including death or hospitalization 
of a participant, will be reported to the IRB, Safety Officer, and NIA Program Officer within 24 
hours of the PI’s knowledge of the SAE.  
Dr. Greysen as the study principal investigator will be responsible for monitoring participant 
safety, data quality/confidentiality, and evaluating the progress of the study on a daily basis in 
conjunction with study staff. An NIA-approved SO will have the role/responsibility of reviewing 
the entire IRB-approved study protocol regarding subject safety and analysis, the informed 
consent document regarding applicability and readability, and participant recruitment and 
retention milestones. At the time of interim analysis (50% enrollment), the study team will 
prepare a safety report to be reviewed by the SO. 
  
 
11.7 Risk/benefit  
 
 
11.7.1 Potential study risks 
There are minimal risks to participants in this study. The potential risks to study participants 
include: breach of confidentiality and privacy as information about each participant including 
their physical activity and health will be recorded; the possibility that answering certain 
questions may make the participant feel slightly uncomfortable; excessive physical activity could 
lead to muscle soreness or injury; some skin irritation or rash from wearing the Fitbit watch, 
although this occurs rarely; increased in physical activity (walking) may increase the risk of 
falling, although this is also very rare. 
We will minimize this risk of confidentiality breach by linking individual identifying information 
with participant ID numbers only in one single secure file that will only be accessed by the study 
team in the case of an adverse medical event, participant dropout, or if otherwise deemed 
necessary by the Principal Investigator. All other identifying information will be discarded after 
initial contact with the Study Coordinator. All other members of the research team will be able to 
view only participant ID numbers.   
 
 
11.7.2 Potential study benefits 
Through participation in this study, each participant will have the potential to increase their 
physical activity, which could improve their health and reduce their risk for cognitive and 
functional decline. If this approach is effective, it could have tremendous benefits for society if 
adopted on a wide scale to help individuals increase physical activity. It is expected that other 
people will gain knowledge from this study and that participation could help understand how to 

effectively motivate people to become more physically active. Participants may also receive no 
benefit from their participation in the study. 
 
 
11.7.3 Risk/benefit assessment 
Anticipated risks of this study should be minimal and the risk/benefit ratio is very favorable. To 
minimize the chance for serious and unexpected adverse events, study participants will be 
screened through exclusion criteria. Participants will be told that increased physical activity may 
improve their health and reduce their risk of cognitive and functional decline. 
11.7.4 Alternatives to participation 
Participants do not have to be enrolled in the study in order to participate in activities to promote 
physical activity. 
 
 
11.8 Resources necessary for human research protection  
In addition to efforts of the study investigators (PI Greysen and Co-I Karlawish), this study will 
be supported by research staff including a Clinical Research Coordinator (50% total effort) and 
analyst (25% effort). The CRC has participated in previous research trials using FitBit devices 
and remote monitoring of physical activity by Way to Health. The CRC has also participated in 
preparation of this study protocol and the PI will oversee execution of this protocol through 
weekly check-ins and ad hoc meetings as needed. The CRC has office space dedicated in the 
Division of General Internal Medicine (Blockley Hall) which is adjacent to the PI’s office. The 
office includes a Penn-issued computer with network access. Since this study will be conducted 
completely virtually, there are no specific facilities other than office space and computing that 
are needed to conduct this study. 
BIBLIOGRAPHY AND REFERENCES CITED 
1. 
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. 
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2. 
Erickson KI, Hillman C, Stillman CM, et al. Physical Activity, Cognition, and Brain Outcomes: A 
Review of the 2018 Physical Activity Guidelines. Med Sci Sports Exerc. 2019;51(6):1242-1251. 
3. 
Northey JM, Cherbuin N, Pumpa KL, Smee DJ, Rattray B. Exercise interventions for cognitive 
function in adults older than 50: a systematic review with meta-analysis. Br J Sports Med. 
2018;52(3):154-160. 
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