Trial Design
We will recruit 140 older adults with SCD to this feasibility, factorial RCT of exercise and diet interventions. Following initial contact and consent, participants will attend a virtual screening visit to further assess eligibility. If deemed eligible, participants will attend two baseline virtual assessments which will index medical history and demographic information, and assess thinking abilities, physical function, and quality of life. After participants complete both baseline assessments, they will be randomized into one of four intervention arms and will receive a combination of two of the following: Aerobic and Resistance Exercise (EX); Diet Counselling (DIET); Brain Health Education (ED); and/or Stretching and Toning (STRETCH). The four intervention arms include: 1) EX and DIET; 2) EX and ED; 3) STRETCH and DIET; or 4) STRETCH and ED. The two virtual assessments completed at baseline will be repeated at post-intervention (6 months) and follow-up (12 months). See Fig. 1 for the study flow chart.
This study has received ethics approval by the University of Waterloo Research Ethics Board (#44616) and by the Baycrest Research Ethics Board (#23–24). The Lifestyle, Exercise, and Diet (LEAD 2.0) study is registered with the US National Institutes of Health clinical trials registry (ClinicalTrial.gov identifier NCT06078748). This report complies with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement.
Figure 1. Study flow chart
[Insert Fig. 1 here]
Study Setting
This study will be conducted virtually, allowing for the recruitment of participants across four provinces (Saskatchewan, Manitoba, Ontario, and Quebec) that are within a 2-hour time zone. Intervention and assessment sessions will be conducted over the Zoom® Healthcare platform. The study sites coordinating and conducting assessment and intervention sessions are the University of Waterloo, Waterloo, Ontario, Canada and Baycrest Academy for Research and Education, Toronto, Ontario, Canada. Participants will join the sessions using an electronic device (computer, tablet) from a place of their choosing, but most often from their home.
Eligibility Criteria
Participants will be 65–85 years old and meet criteria for SCD by: a) Answering Yes to both of the following questions i) Do you feel like your memory or thinking is becoming worse?, ii) Does this worry you? (39, 40); b) Having no objective cognitive impairment as indicated by i) a global Clinical Dementia Rating (CDR) of 0.5 or lower, ii) a Blind Montreal Cognitive Assessment (MoCA) total score of > 17. Participants will also meet the following criteria:
1) Be able to communicate in English
2) Be residents of Saskatchewan, Manitoba, Ontario, or Quebec
3) Have low physical activity levels (< 75 min./week of aerobic moderate to vigorous physical activity on the Canadian Society for Exercise Physiology’s (CSEP) Get Active Questionnaire (41))
4) Be screened safe to participate in moderate exercise using the CSEP Get Active Questionnaire (41) or physician approval to engage in moderate intensity exercise without in-person supervision
5) Have low diet quality (below Canadian older adults’ median intake of fruits, vegetables, nuts and fish, reported using our Diet Screening Questionnaire targeting the Brain Health Food Guide criteria, used in the LEAD 1.0 pilot (42)
6) Be able to participate remotely (i.e., availability of, or ability/willingness to adopt a computer or tablet with high-speed internet/data networks).
Participants will be excluded if they have a history of dementia, stroke or other significant known chronic brain disease, have had chemotherapy or radiation to the head/neck in the past year, have sensory impairments that would impede participation in the intervention or assessments, have current major or unmanaged psychiatric disorder or history of hospitalization for a psychiatric disorder, have ongoing alcohol or drug abuse that in the opinion of the investigator may interfere with the participant’s ability to comply with the study procedures, or have contraindications for exercise as determined by the CSEP Get Active Questionnaire (41).
Participants will also complete the Comprehensive Executive Function Inventory for Adults (CEFI-Adult) during the screening process. The research team originally intended to screen participants for executive SCD but decided to screen for general SCD one month into the study due to a low recruitment rate. In secondary analyses, we will determine whether outcomes differ between those with or without executive SCD.
Recruitment Process and Strategy
Recruitment of participants began in July 2023 and is expected to be completed in December 2024. The target is to recruit 140 participants across 5 waves, using a variety of recruitment strategies to increase the likelihood of reaching diverse older adults: directed mailings, social media, websites, radio/newspaper advertisements, research and community organization email lists, partner websites and centers, and outreach to physician/seniors’ groups. Participants will also be recruited from targeted research pools and partners email lists including the investigators’ research institutes, the Canadian Consortium for Neurodegeneration in Aging (CCNA), and other project partners.
Potential participants will be contacted by telephone by a member of the research team who will go through the recruitment script to describe the study and screen for eligibility. During this call, a brief assessment for SCD will be conducted. Eligible participants will be sent an electronic version of the letter of information and consent form and will schedule their second screening visit to rule out objective cognitive impairment. All eligible participants will then complete virtual assessments 1 and 2 within six weeks of their program start date. Once the assessments are completed, participants will be randomized into one of the four study arms. See Table 1 for an outline of the assessments and timeline.
Table 1
Schedule of study assessments.
| Study Timeline |
| Enrollment | Baseline | Post-Int. | Follow-Up |
Timepoint | -t1 | t1 | t2 | 6-months after t2 assessment, t3 |
SCREENING & ENROLLMENT: | | | | |
Screening Visit #1 | X | | | |
Informed Content | X | | | |
Screening Visit #2 | X | | | |
VIRTUAL ASSESSMENT 1: | | | | |
Sociodemographic Information | | X | | |
Language Proficiency and Acquisition | | X | | |
Medical and Mental Health History | | X | X | X |
Current Medications | | X | X | X |
Technology Proficiency Survey | | X | | |
PASE | | X | X | X |
EPSA | | X | X | X |
Waist Circumference | | X | X | X |
5x Sit to Stand Test | | X | X | X |
SF-36 | | X | X | X |
CES-D | | X | X | X |
GAI | | X | X | X |
VIRTUAL ASSESSMENT 2: | | | | |
CBS Double Trouble Stroop Test | | X | X | X |
CBS Monkey Ladder | | X | X | X |
CBS Feature Match | | X | X | X |
CBS Paired Associates Task | | X | X | X |
RAVLT | | X | X | X |
Note. PASE = Physical Activity Scale for the Elderly; EPSA = Eating Pattern Self-Assessment; SF-36 = Short-Form 36; CES-D = Center for Epidemiological Studies Depression Scale; GAI = General Anxiety Inventory; CBS = Cambridge Brain Sciences; RAVLT = Rey Auditory Verbal Learning Test |
Table 1. Schedule of study assessments.
[Insert Table 1 here]
Randomization and Blinding Procedure
Participants will be randomly assigned (1:1:1:1) after baseline assessments, stratified by gender (man/woman, and if sufficient in number, non-binary/self-described) and balanced within blocks of variable size (4 or 8) to avoid predictable participant allocation. Eligible partnered couples will be randomized together. The randomization sequence will be computer-generated and maintained by an assistant not affiliated with the study. Once baseline assessments are complete, the research coordinator will provide the participant ID to the randomization assistant who will inform the coordinator of the group allocation, which will be communicated to the participant. Participants will start the trial in waves of 24 to 32 (6 to 9 people per group; every 3 months) to ensure sufficient sample size for group dynamics and social support.
Assessors will be blinded to group assignment and participants will be asked not to mention their group assignment to assessors. Standardized instructions will be provided for assessments. To keep participants blinded from the study hypotheses and to minimize group effect expectations, the content of the intervention and the wording of recruitment documents and consent forms will not convey the differences between EX and STRETCH. Participants will be told that the groups will differ in the type of brain health education that is provided (DIET versus ED).
Trial Interventions
Participants will engage in two virtual group sessions (2 hours and 1 hour in length) and one independent session (1 hour) per week. The breakdown of each group’s weekly sessions is shown in Table 2. The balance across intervention components varies between the first four months and last two months of the trial, whereby the Goal-Setting component will primarily focus on DIET in the first four months and EX in the last two months. Furthermore, participants will be encouraged to integrate more of their exercise within community settings (i.e., join an exercise class rather than relying on the study video) in the last two months of the intervention.
Table 2
Intervention time by study arm Phase 1: Months 1–4
Group | Group Session 1 (30 min) | Group Session 1 (90 min) | Group Session 2 (1 h) | Independent Session (video) (1 h) |
EX + DIET | EX | DIET + GOAL | EX | EX |
EX + ED | EX | ED | EX | EX |
STRETCH + DIET | STRETCH | DIET + GOAL | STRETCH | STRETCH |
STRETCH + ED | STRETCH | ED | STRETCH | STRETCH |
Phase 2: Months 5–6
Group | Group Session 1 (30 min) | Group Session 1 (90 min) | Group Session 2 (1 h) | Independent Session (1 h) |
EX + DIET | EX | EX GOAL + DIET | EX | EX (home/community) |
EX + ED | EX | EX GOAL + ED | EX | EX (home/community) |
STRETCH + DIET | STRETCH | ED + DIET | STRETCH | STRETCH (video) |
STRETCH + ED | STRETCH | ED | STRETCH | STRETCH (video) |
Orientation
Prior to the first intervention session, participants will meet with the instructor in a one-on-one Zoom® call. Participants will receive a summary of how to use ZoomⓇ (e.g. opening ZoomⓇ, connecting video and audio, settings, mute/unmute, using the chat) and be provided with a telephone number/email to contact a study volunteer for technology help during classes. The instructor will gather the participant’s emergency contact or any other relevant information that may be necessary in case of an emergency or to inform exercise modifications (i.e., medical conditions, symptoms, medications). They will then help the participant choose a safe exercise location and a good position for their device. Participants will be encouraged to use a bright room with space for exercise and a hard non-slippery surface free from clutter and any tripping hazards. The device (computer or tablet) should be placed in a position where the instructor will be able to see them exercising. The participant will be asked to mark off the placement area so they know exactly where to put their device each time. The instructor will then go through a checklist of what to wear (running shoes and comfortable clothing) and what to have with them (phone within reach, water bottle, chair, resistance bands, and exercise mat). Prior to the intervention starting, participants will be mailed resistance bands and an exercise mat.
The instructor will also describe the general class routine (length, format, group-based) and discuss safety information while exercising (including working within own limitations, as well as to immediately notify instructor if feeling lightheaded, dizzy, unwell, chest pain, muscle pain). The emergency procedures will also be discussed, and participants will receive a copy of this procedure via email. Participants will be asked to leave their webcams on and to notify the instructor with a wave if they are leaving the screen for a non-medical reason. If participants leave the screen without notice, the instructor will call them and then call emergency services if an emergency is suspected.
The instructor will also complete the Participant Intake Form [see Supplementary Material 2] with each participant. The instructor will use this information (along with the recommendations made by a participant’s physician, if applicable), to recommend that the participant complete EX/STRETCH seated or standing.
EX Intervention
Participants in the exercise intervention (EX + DIET or EX + ED) will complete 2.5 hours of moderate intensity aerobic, resistance, and balance exercise per week. EX will be instructed by a Certified Exercise Physiologist (CEP) or a Registered Kinesiologist with a volunteer also being present for assistance.
At the start of each EX session, the instructor will welcome the group and the volunteer will record attendance. The volunteer will remind participants of safety precautions and will confirm that participants have a phone within arm’s reach. The 30 minute EX session will include a 5-minute warm-up, 20 minutes of aerobic training, and 5 minutes of balance training and cool-down. The 60-minute EX session will include a 5-minute warm-up, 20–25 minutes of aerobic training, 20–25 minutes of resistance training, 5 minutes of balance training, and a 5-minute cool-down. The virtual video session will be pre-recorded, have similar composition to the 60-minute EX session, and will be led by the same instructor. In months 5 and 6 of the intervention, participants will be asked to replace the video session with home- or community-based exercise of their choosing, with encouragement to match the intensity and duration of the video sessions.
Aerobic exercise will include exercises that are appropriate for older adults and can be completed at home, such as marching on the spot, walking forward/backwards, side stepping, and heel/toe taps. Resistance exercises will follow the Cardiac College recommended resistance exercises for older adults (43), which target major muscle groups including the legs, chest, back, shoulders, and core, and use body weight, home objects, and study-provided resistance bands to increase challenge. Participants can complete exercises seated or standing, according to their own preference or based on recommendation by the instructor (along with the recommendations made by a participant’s physician, if applicable). The difficulty of exercise sessions will be progressed over the study, adapted to the range of fitness, strength, and ability. Participants will be instructed to target an intensity of 3 or less during the first several weeks, and 4 on the 10-point RPE scale during the remainder of the program (equivalent to moderate intensity; rated on the last 2 to 3 repetitions for resistance training) (44).
STRETCH Control: The STRETCH sessions will be time/frequency-matched to EX sessions (2.5 hours/week: 1.5 hours in virtual group sessions; 1 hour in virtual video session) to control for social aspects and placebo effects of EX. The STRETCH session will start in the same way as the EX session. Each 30-minute STRETCH session will include a 5-minute warm-up, 5 minutes of balance exercises, and 20 minutes of stretching and toning. Each 60-minute STRETCH session will include a 5-minute warm-up, 5 minutes of balance training, and 50 minutes of stretching and toning. Difficulty will not be progressed. STRETCH sessions will also be led by a CEP or Registered Kinesiologist, with a volunteer present for assistance. Video sessions will be pre-recorded by the same instructor. Again, participants can complete exercises seated or standing, according to their own preference or based on recommendations by the instructor (along with the recommendations made by a participant’s physician, if applicable).
DIET Intervention
The DIET intervention includes one session per week, delivered by a Registered Dietitian. The weekly DIET session will be 90 minutes during months 1 to 4, and 30 minutes in months 5 and 6. The DIET intervention was developed by the research team, emphasizing foods identified as supporting executive function, memory, and other cognitive abilities in prior research and included in the Brain Health Food Guide (45) [see Supplementary Material 4]. DIET integrates recommendations from the Mediterranean diet and the DASH diet as well as individual foods that have been associated with brain health (46–49). Beneficial food groups include vegetables (and raw/leafy green vegetables, cruciferous vegetables particularly), fruits (berries particularly), unsalted nuts (walnuts particularly) or natural nut butters, fish or seafood, fatty fish, beans and legumes. Foods to limit include meat and poultry, red or processed meat, butter, cream, or high fat dairy spreads, white bread, and processed foods. Individuals in the DIET group will fill out the Eating Pattern Self-Assessment monthly to help with goal setting.
ED Control
The ED control program was adapted from the placebo condition of the Discovery program used by the Canadian Consortium on Neurodegeneration in Aging (CCNA) sub-study ENGAGE (NCT#03271190) for their placebo intervention (50), which also served as a diet placebo condition in the LEAD 1.0 pilot (42). These classes are designed to be of equal intensity and social interaction/engagement compared to the DIET sessions and have been manualized to ensure consistency between instructors. During these sessions, participants will engage in group discussion and receive information on the brain and cognitive processes, the effect of age on cognition, and tips to promote healthy aging. This will include lectures, watching documentaries and participating in various games.
Goal-Setting
All arms that receive DIET and/or EX interventions will also receive the Goal-Setting training, with goals focused on diet and/or exercise (51, 52). This meta-cognitive skill-acquisition intervention is based on the Cognitive Orientation to daily Occupational Performance (CO-OP) approach (51), participants’ goal setting, behavioural self-monitoring, and problem-solving skills, three behaviour change techniques commonly and effectively used to promote physical activity and improve dietary behaviours among older adults (53–56). Participants are taught to use a global strategy (Goal-Plan-Do-Check) to facilitate individualized exercise or diet goal setting and develop plans to achieve them, through an iterative problem-solving process (51, 52). To support skill development, the goal setting intervention will use guided discovery methods, a series of hierarchical questions or guiding statements that lead the participants to discover and articulate their thoughts or actions (51).
Participants will set two individualized goals that align with exercise and/or diet recommendations, depending on their intervention group (e.g., 20-minute walk every day; eat legumes 3 times per week) and develop a concrete plan to attain each goal (e.g., walk with a friend in the mall; learn to make lentil soup and hummus). The facilitator will guide the participants to consider potential barriers to goal achievement (e.g., cost of food, poor weather, fatigue), and problem solve ways to overcome them. In consequent sessions, participants will be guided to monitor their progress (e.g., did the plan work? what should be changed?) and iterate their plan as needed. The last month of goal training will focus on developing goals and plans for the follow-up period so that behaviour change gains can be integrated into daily life. Those who are not in DIET or EX interventions will not receive Goal-Setting training, but will receive additional ED instead.
Promoting Adherence and Retention
To promote retention and reduce the incidence of dropouts over the 12-month follow-up period, the intervention coordinator will remain in close contact with the participants and be available by phone to discuss potential issues. The team will also contact participants in advance of their 12-month follow-up assessments. Participants who withdraw from the study will be invited to attend their follow-up assessments.
Primary Outcome Measures
Feasibility: Recruitment, Adherence, Retention
i) Recruitment
A research coordinator will be responsible for logging recruitment activities as participants contact the study email or phone number. The research coordinator will document the following information of each participant: name, phone number, email, date of first contact, how they heard of the study, and whether they passed telephone screening. For participants that pass initial screening, they will be scheduled to meet with an assessor for a second screening and to provide consent. Upon completing the second screening session, the research coordinator will document whether they passed or failed screening. Recruitment feasibility will be determined by the average number of participants recruited per month (target: ≥9 participants per month).
ii) Adherence
Instructors will keep a detailed attendance record for each component of each session (EX/STRETCH and DIET/ED). The target is ≥ 75% of EX and ≥ 75% of DIET sessions completed. Adherence will be measured through subjective participation scores that are completed by the instructor and volunteer of each session, as well as by self-reported RPE ratings provided each session by participants in the EX groups. For each EX/STRETCH and DIET/ED component, participants will be confidentially scored on a scale from 1–3. A score of 3 indicates that the participant actively followed along with all exercises/stretches or DIET/ED content and participated in exercises/stretches or listened or contributed greater than 80% of the session. A score of 2 indicates that a participant engaged/contributed to 50–80% of the session and a 1 indicates that a participant engaged in less than 50% of the session. Self-reported attendance records for the independent sessions will also be collected, noting RPE rating (for EX groups), and any symptoms experienced during EX and STRETCH. For diet quality specifically, adherence will be measured through adherence to the Brain Health Food Guide recommendations and will be assessed using the Eating Pattern Self-Assessment (EPSA) (45).
iii) Retention
Patients will be considered “non-completers” upon confirmation from a participant that they no longer wish to participate or are unable to participate. When a participant drops out of the study, the instructor will inform the research coordinator who will document withdrawals. The research coordinator will categorize reasons for non-completion as medical or non-medical. The feasibility target for retention is defined as ≥ 80% of participants with complete 6-month assessments.
Secondary Outcome Measures
Each participant will complete two assessments at baseline (t1), post-intervention (t2), and 6 months post intervention (t3) (see Fig. 1 for overview). All assessments will take place over Zoom® with a research assistant or coordinator who is blinded to group allocation.
At virtual assessment 1 (55 minutes) the following will be assessed: 1) Demographics: age, sex, gender, race and ethnic origins, education, marital status, type of residence, geography of residence (urban/rural), socioeconomic status; 2) Medical and mental health history and current use of medications; 3) Technology proficiency assessed using 10 questions adapted from AGE-WELL’s Canadian Attitudes toward Technology and Aging Questionnaire (57); 4) Functional strength assessed with the 5-time sit-to-stand test, which is a validated test of lower body function and strength among older adults (58). The participant will be timed as they stand from a seated position 5 times using a chair of standard height (same chair at each assessment); 5) Physical activity assessed using the Physical Activity Scale for the Elderly (PASE) which is valid among older adults aged 65–100 years and will be used to characterize habitual physical activity, and maintenance of physical activity levels during the post-intervention period (59); 6) Health-Related Quality of Life (QOL) measured using the SF-36 questionnaire (60), which will be used to develop weightings for quality-adjusted life-years (for the full-scale trial). The SF-36 also includes 8-scale scores that can be grouped into physical health QOL and mental health QOL. The SF-36 has been shown to be a valid and practical instrument to assess the quality of life of older adults living at home (61); 7) Psychological health including depressive symptoms measured using the Center for Epidemiological Studies-Depression scale (CES-D) (62) and perceived anxiety measured using the Geriatric Anxiety Inventory (GAI) (63). The CES-D has demonstrated high validity and reliability among older adults (62, 64). The GAI has demonstrated a strong ability to identify geriatric anxiety, with studies reporting a high internal consistency and validity of the questionnaire (63, 65); 8) Waist circumference assessed as a simple indicator of vascular risk (66). The assessor will oversee the measurement, ensuring the tape measure is in the correct position. This measurement will be taken a second time to ensure accuracy, with both values will be recorded and an average of both values being used; 9) Diet Quality measured using the Eating Pattern Self-Assessment (EPSA) which collects self-reported intake of the 15 targeted food items from the BHFG. In addition to t1, t2, and t3, the EPSA will also be administered monthly to participants in the DIET group to help with goal setting, while it will be administered mid-way through the program for participants in the ED groups. At post-intervention, participants will complete a survey to gather feedback about their experience in the program.
At virtual assessment 2 (30 minutes) executive function will be assessed by a composite measure of executive function, consisting of the Cambridge Brain Sciences (CBS) Double Trouble (Stroop), Monkey Ladder (visuospatial working memory), and Feature Match (attention speed) tasks (67). Memory will be assessed by delayed recall on the Rey Auditory Verbal Learning Test (RAVLT) (68) and the CBS Paired Associates task (67). These tests were chosen as they measure the cognitive domains of interest and have been validated for remote delivery (69–71).
Sample Size
A recent meta-analysis of exercise on cognition found Cohen’s d effect sizes between 0.27 and 0.36, dependent on combinations of exercise mode, frequency, duration, and outcome (14). Effect sizes for diet interventions are highly variable depending on the intensity of the intervention. The most similar published diet intervention was in a factorial RCT of exercise and diet (without a goal-setting component) that found an effect size of 0.32 for exercise and 0.30 for diet (72). The intensity of the current study intervention is higher than in this prior study, and it is expected that the goal-setting will increase adherence. However, virtual delivery may weaken adherence. As a result, an effect size of 0.30 was chosen for sample size estimates.
Power analysis was estimated based on the analysis plan described below. It is estimated that 88 participants are needed per intervention arm (total of 364 participants) to detect EX (d = 0.3) and DIET (d = 0.3) effects with an alpha level of 5% and 80% power. With 10% dropout, 404 participants are needed for a full-scale trial over 3.5 years. As a result, for this feasibility trial, 140 participants will be recruited over 1.25 years to test the feasibility of the rate of recruitment that would be required for the full trial. Interim analysis of feasibility will be performed after the first three waves complete the 6-month assessment.
Data Handling
Investigators and study staff will collect only the information needed for this study. Data will be stored in password protected files on computers, and in locked rooms. Data related to questionnaires will be collected using Qualtrics software (August 2023) and stored on an encrypted drive. All personal identifying information will be removed from the data and will be replaced with an ID code. Following completion of the study, data will be made available on an open science platform (platform yet to be determined, with participant consent) so that other researchers will have the opportunity to validate and replicate the results. All data shared in an open science framework will be de-identified and only study staff will be able to link this data to any personal identifying information.
For the memory and learning tests, there may be audio recordings to ensure that the researcher scores the test results accurately. These tests will also be saved with an ID code so that names cannot be identified and they will be stored until data analysis is complete.
Safety and Monitoring Procedures of Adverse Events
Procedures are in place to monitor adverse events that participants may experience during the intervention. Grading and categorization of adverse events will be conducted using the Common Terminology Criteria for Adverse Events (73). Participants will be queried about adverse events at each session and study visit. Study staff are instructed to contact the University of Waterloo and Baycrest Research Ethics Boards for any adverse events that occur during the study. Adverse events for this study are defined as any undesirable experience that occurs to a participant during the 6-month intervention, regardless of whether they are perceived to be related to the intervention, and whether they are an expected consequence of the intervention. For adverse events that occur which are perceived to be related to the intervention, study physicians will be alerted. If it is unclear whether an adverse event is study related, the event and the conditions will be shared with study physicians.
Analysis
Analysis of primary objectives related to feasibility outcomes will be descriptive. ‘Success’ will be based on predetermined criteria outlined in Objectives and Hypothesis which included: 1) Recruitment: ≥ 9 participants/month over 1.25 years; 2) Adherence: a) ≥ 75% of Aerobic and Resistance Exercise (EX) sessions and ≥ 75% of Diet Counselling (DIET) sessions are completed; b) improvement in diet quality at 6-months compared to baseline; 3) Retention: ≥ 80% of randomized participants complete the 6-month assessment of executive function. Overall, ‘success’ will indicate that the protocol is adequately robust to proceed to a large RCT with small or no adaptations, and failure to meet these targets indicating a need for substantial change before proceeding. Preliminary analyses of feasibility outcomes will be conducted at the end of year 2 by an independent statistician when the first three waves complete their 6-month assessment. If the data support feasibility, the research team will apply for funding to roll directly into the definitive trial.
Full analyses will be conducted once all participants have completed their 12-month follow-up assessments. Analyses will explore whether feasibility outcomes vary by gender as research suggests that exercise and diet preferences vary by gender (74, 75). Feasibility outcomes will also be described among women and men, and among non-binary and other gender groups if possible.
Analyses will also explore whether other demographics, geographical location, or technology access predict adherence. Characteristics of the participants who withdraw and reasons for withdrawal will be analyzed and intent-to-treat analyses will be used. In addition, effect sizes for each will be determined for the future, full-scale trial by gender. The future full-scale trial, we will also examine whether effectiveness outcomes vary by biological sex, where the relationship between exercise and cognition appears to be stronger for females than for males (76). Analyses of secondary objectives will be conducted from both intention-to-treat and per protocol analyses (to understand potential effectiveness in relation to adherence). To evaluate the effectiveness of EX and DIET, an analysis of covariance (ANCOVA) will be conducted, with the post-intervention composite measure of executive function as the outcome variable and baseline executive function as a covariate. Explanatory variables will include whether the participant received EX training and whether they received DIET training. Change in the EX or DIET association with executive functioning exceeding 10% will be reported as a salient mediating factor.