Digital Lifestyle Coaching for Alzheimer's Disease Prevention in APOE4 Carriers (WellderlyBrain)

Wellderly Brain - Alzheimer's Disease Prevention With Lifestyle Coaching Intervention: A Randomized Clinical Trial

Wellderly Brain is a randomized, direct-to-participant trial evaluating whether a virtually delivered, multidomain lifestyle coaching intervention can favorably impact plasma biomarkers of Alzheimer's disease (AD) in adults aged 60-80 with APOE4 positivity or elevated polygenic risk. Participants are recruited through 23andMe and enrolled via the MyDataHelps platform. Following genetic eligibility screening, 1,200 participants will be randomized to either a digital lifestyle coaching arm (UCardia) or an education-only control arm. The intervention consists of 16 virtual coaching sessions delivered over 52 weeks. All participants will wear an Oura Ring for continuous health monitoring and provide dried blood samples at baseline, 6 months, and 12 months for plasma p-tau217 and proteomic profiling via the NULISAseq CNS Disease Panel. Saliva samples will be collected for epigenetic aging analysis. The study duration is 14-16 months per participant.

Study Overview

• Status: Not yet recruiting
• Conditions: Mild Cognitive Impairment (MCI); Alzheimer Disease (AD)
• Intervention / Treatment: Behavioral: Education

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katie Quartuccio; Phone Number: 858-784-5219; Email: kquartuccio@scripps.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Translational Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Current 23andMe Research participant with APOE4 positivity genetic variant
• Age 60 to 80 at time of consent
• Have access to an Android or Apple iPhone smartphone device and able to download study apps
• Lives in the United States and able to send and receive US Mail
• Able and willing to perform a self-administered saliva test at screening*for organic outreach only.
• Able and willing to perform a self-administered finger prick blood collection at three time points throughout the study.

Exclusion Criteria:

• Non-English speaking
• Lives outside of the United States
• Currently taking or planning on taking GLP-1 medications (Exenatide, Liraglutide, Albiglutide, Dulaglutide, Semaglutide or Tirzepatide) within the next 12 months
• Established diagnosis of Mild Cognitive Impairment, Alzheimer's Disease or other Neurodegenerative Disease (Parkinson's Disease, Amyotrophic Lateral Sclerosis, Huntington's Disease, Multiple Sclerosis or Frontotemporal Dementia).
• Current or past Oura Ring user (any Oura Ring use in the last 12 months)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Virtual Lifestyle Coaching	Behavioral: Education; Treatment group will recieve 16 virtual lifestyle coaching sessions with a certified wellness coach over the course of 52 weeks. Education will focus on activity and sleep (with guidance from Oura ring) and anti inflammatory diet.
No Intervention: Standard of Care; Participants will receive an Oura Ring with daily metrics of sleep and activity but no supplemental education of guidance on improving their scores. They will have access to current standard of care worksheets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pTau217 Concentration	Plasma phosphorylated tau 217 (pTau217) concentration will be measured from self-collected dried blood spot samples at three timepoints across the 12-month active monitoring period. Both absolute concentration at each time point and change from baseline will be assessed.	Month 1, Month 6, Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite proteomic brain-aging score	A composite proteomic brain-aging score will be derived from proteomic biomarkers associated with biological brain aging, measured via dried blood spot samples collected from participants. The score represents estimated biological brain age relative to chronological age; lower scores indicate a younger biological brain. Analysis will be restricted to participants who return all required dried blood spot samples.	Month 12
Neuropsychological Test Composite Score	A composite neuropsychological score will be derived from repeated administration of validated online cognitive assessments, including the Stroop Test, Processing Speed Assessment Test (PSAT), and Trail Making Test, spanning cognitive domains of attention, processing speed, executive function, and cognitive flexibility over time. The direction of the composite score will be defined in the statistical analysis plan. Both composite score at each time point and change from baseline will be assessed.	Month 1, Month 3, Month 6, Month 9, Month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Activity	Physical activity will be assessed continuously via Oura Ring throughout the 12-month study period. Metrics may include daily movement, step count, activity volume, energy expenditure, and overall activity score. Both metric values at each time point and change from baseline will be assessed.	Continuously throughout study completion, an average of 1 year
Patient Reported Physical Activity	Self-reported physical activity will be assessed monthly via participant questionnaire measuring average duration, frequency, and intensity of physical activity performed during each assessment period.	Once per month throughout study completion, an average of 1 year
Sleep Health via Oura Ring Sleep Score	Sleep health will be assessed continuously via Oura Ring wearable device throughout the 12-month study period. Sleep metrics include total sleep duration, sleep efficiency, REM sleep, deep sleep, sleep latency, sleep timing, restlessness, breathing regularity, blood oxygen saturation, and heart rate variability (HRV), which are combined to generate the Oura Sleep Score (range: 0-100; higher scores indicate better sleep quality). Both Sleep Score at each time point and change from baseline will be assessed.	Continuously throughout study completion, an average of 1 year
Patient Reported Sleep Quality	Subjective sleep quality will be assessed monthly via an 11-point rating scale (range: 0-10) measuring how refreshed participants feel upon waking. Higher scores indicate better subjective sleep quality.	Once per month throughout study completion, an average of 1 year
Heart Rate Variability	Heart rate variability (HRV) will be assessed continuously via Oura Ring wearable device throughout the 12-month study period. Higher HRV trends over time are interpreted as indicative of better cardiovascular health. Both HRV values at each time point and change from baseline will be assessed.	Continuously throughout study completion, an average of 1 year
Dietary Changes	Self-reported dietary behaviors will be assessed monthly via participant questionnaire. Measures include dietary pattern adherence (e.g., specific diet type followed), macronutrient and food group intake changes (e.g., protein and vegetable consumption), and self-reported weight changes throughout the study period.	Once per month throughout study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Scripps Translational Science Institute
• Collaborators: 23andMe, Inc.; Sapient Bioanalytics; TEAL Rise; Alamar Biosciences; Oura Ring, Inc
• Investigators: Principal Investigator: Eric J Topol, MD, Scripps Translational Research Institute

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): July 6, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimers; Alzheimer Disease (AD)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Socioeconomic Factors; Population Characteristics; Educational Status
• Other Study ID Numbers: ScrippsRTI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The investigators may share the coded study data with researchers outside of Scripps Research. Before doing so, they will ensure that nothing in the data can identify the participant directly.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No