Predicting pre-dementia progression in APOE‑ε4 carriers
Assessing Tools That Predict and Stage Mild Cognitive Impairment
This project will try a combined genetic, blood, and wearable-monitoring model to see if it can predict which cognitively normal or very mildly impaired adults aged 55+ with an APOE‑ε4 gene will develop biomarker-confirmed MCI within 24 months.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 100 (estimated) |
| Ages | 55 Years and up |
| Sex | All |
| Sponsor | Prevention Research Consortium Corp. Academic / other |
| Drugs / interventions | Radiation |
| Locations | 1 site (San Diego, California) |
| Trial ID | NCT07516119 on ClinicalTrials.gov |
What this trial studies
This observational, first-in-human cohort follows APOE‑ε4–positive adults aged 55 and older for two years to test a multimodal "Progression and Risk" (P&R) model. The P&R model integrates polygenic risk scores from existing whole-genome or high-density genotyping, plasma proteomics (including pTau217), other omics, digital cognitive tests, wearable data (e.g., Oura Ring sleep/activity), and EMR/lifestyle risk scores. Researchers will compare the full multimodal model's ability to predict conversion to pTau217-positive MCI Stage I within 24 months against simpler models like PRS alone or standard clinical risk factors. Participants must already be APOE‑ε4 carriers with prior genomic data and be cognitively normal or very mildly impaired at baseline, and no investigational interventions are administered because the study is observational.
Who should consider this trial
Good fit: Ideal candidates are adults aged 55 or older who already carry at least one APOE‑ε4 allele, are cognitively normal or very mildly impaired, and can provide existing whole-genome or high-density genotyping data and attend the San Diego site.
Not a fit: People without an APOE‑ε4 allele, those with more advanced cognitive impairment, or individuals unable or unwilling to provide prior genomic data or to attend the study site are unlikely to benefit from this research.
Why it matters
Potential benefit: If successful, this approach could identify people at imminent risk of Alzheimer's-related MCI earlier and more accurately, enabling closer monitoring or entry into prevention trials.
How similar studies have performed: Blood biomarkers such as pTau217 and polygenic risk scores have shown good predictive performance in prior studies (AUCs around 0.8–0.9), but integrating these with wearables and digital assessments in a single multimodal model is largely novel and first-in-human here.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: Age Age 55 years or older at enrollment. APOE Genotype Documented carrier of at least one APOE ε4 allele, based on prior testing (e.g., clinical APOE testing, prior genetic panel, research cohort genotyping, or direct-to-consumer testing). Existing Genomic Data for PRS Whole-genome sequencing (WGS) data already completed, with willingness to provide existing WGS data files (e.g., VCF, FASTQ, or equivalent) to the study team for Alzheimer's disease polygenic risk score (PRS) calculation; or If WGS is not available, prior high-density or targeted genotyping array data covering Alzheimer's disease risk loci, with willingness to provide these data for PRS calculation (feasibility of array-based PRS will be evaluated case-by-case). Note: The study does not perform APOE genotyping or WGS as part of the research; these must be completed before enrollment. Cognitive Status at Baseline Cognitively normal or very mildly impaired at baseline, defined by: Digital cognitive assessment and/or Punto Test consistent with a Global Clinical Dementia Rating (CDR) of 0 or 0.5. No clinical diagnosis of dementia. For cognitively normal (CN) and subjective cognitive decline (SCD) participants, staging by the Progression and Risk (P\&R) model (combining PRS, biomarker, and cognitive data) will be applied for risk stratification. Absence of Baseline AD-MCI by Biomarkers Does not currently qualify for Alzheimer's disease-related MCI (AD-MCI), operationalized as no evidence of MCI with plasma or CSF pTau217 level above a validated cutoff for AD-MCI pathology. Capacity and Participation Ability Able to provide informed consent (with capacity assessments and, where applicable, involvement of a legally authorized representative per institutional policy and IRB approval). Able and willing to comply with study procedures, including clinic visits, cognitive testing, and biospecimen collection. Willingness to Use Digital Monitoring Tools Willing to wear and/or carry digital devices for continuous or frequent monitoring (e.g., smartphone app, wearable sensors such as Oura Ring, sleep device), and to participate in app-based cognitive and speech assessments. Data-Sharing Authorizations Willingness to sign data release authorizations allowing the study to obtain existing genomic data (WGS or array) and relevant electronic medical record (EMR) data needed for risk modeling and outcome adjudication. Exclusion Criteria: Baseline Dementia Diagnosis Clinical diagnosis of dementia of any cause at baseline. Major Neurological Disorders Affecting Cognition History of major neurological conditions that in the investigator's judgment may confound cognitive assessment or outcomes, such as: Parkinson's disease. Stroke with residual neurological deficits. Epilepsy with frequent seizures. Major Psychiatric Illness Major psychiatric disorders that significantly interfere with participation or data interpretability, such as uncontrolled major depressive disorder or schizophrenia, as judged by the investigator. Serious or Unstable Medical Conditions Uncontrolled systemic medical illness expected to limit life expectancy to less than approximately 3 years, including but not limited to unstable cardiac, hepatic, or renal disease. Recent Investigational or Disease-Modifying AD Treatments Use of investigational drugs or disease-modifying Alzheimer's therapies within 6 months prior to baseline, if such treatments are likely to confound biomarker trajectories or cognitive outcomes. Inability or Unwillingness to Use Required Digital Tools Lack of Required Genomic Documentation or Refusal to Share Data No prior APOE genotype documenting at least one ε4 allele; or No available WGS or suitable genotyping array data; or Refusal to share existing APOE/genomic data and necessary EMR data with the study team. Baseline MCI with Positive pTau217 Vulnerable Populations Not Targeted Children, prisoners, and pregnant individuals are not specifically targeted and will be excluded from enrollment.
Where this trial is running
San Diego, California
- Foster Carr MD — San Diego, California, United States (Recruiting)
Study contacts
- Principal investigator: Foster Carr, MD — Prevention Research Consortium Corp.
- Study coordinator: Foster Carr, MD
- Email: drcarr@prevention-research.org
- Phone: 8772716078
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.