About this 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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).
Trial design
Parallel
Treatments tested in this trial
Education
BehavioralTreatment 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.
Treatment groups
Trial outcomes
Primary outcomes
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.
Secondary outcomes
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.
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.
Other outcomes
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.
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.
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.
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.
Sponsors and contacts
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Scripps Translational Science Institute
Lead sponsor
Sapient Bioanalytics
Collaborator
TEAL Rise
Collaborator
23andMe, Inc.
Collaborator
Alamar Biosciences
Collaborator
Oura Ring, Inc
Collaborator
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