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

N/ANot Yet RecruitingNCT07646054

Scripps Translational Science Institute1,200 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

1,200

Conditions

Mild Cognitive Impairment (MCI)Alzheimer Disease (AD)

Eligibility

Sex: ALLMin age: 60 YearsMax age: 80 Years

Medical Language ↔ Plain English

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)

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.

Time frame: Month 1, Month 6, Month 12

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.

Time frame: 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.

Time frame: Month 1, Month 3, Month 6, Month 9, Month 12