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Digital memory assessments and plasma pTau217 enable efficient preclinical Alzheimer's trials
Vanderlip CR, Gillen DL, Grill JD, Stark CEL.. The journal of prevention of Alzheimer's disease, 2026-02-06
Topic: Amyloid, tau and blood-test diagnosis
Background Preclinical Alzheimer's disease (AD) trials enroll cognitively unimpaired, amyloid-positive older adults; however, most remain clinically stable over typical trial durations. Limited near-term decline reduces statistical power and drives large sample sizes and high costs. Scalable enrichment strategies capable of identifying individuals most likely to decline are critically needed. Objectives To determine whether a brief digital memory assessment (DMA) and plasma phosphorylated tau 217 (pTau217), individually or combined, identify preclinical AD participants at elevated risk for cognitive and biological progression, and whether such enrichment reduces clinical trial sample-size requirements. Design Analysis of data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study, a multicenter randomized clinical trial with 240 weeks of follow-up. Setting Secondary-prevention trial conducted across sites in the United States, Canada, Australia, and Japan. Participants A total of 1,169 cognitively unimpaired adults aged 65-85 years who were amyloid-positive and completed both a baseline DMA and plasma pTau217 measurement. Measurements Primary outcome was change in the Preclinical Alzheimer Cognitive Composite (PACC) over 240 weeks. Secondary outcomes included Clinical Dementia Rating-Sum of Boxes, Mini-Mental State Examination, Cognitive Function Instrument, and annualized change in amyloid PET, plasma pTau217, and tau PET. Results Participants with both elevated pTau217 and low DMA exhibited the greatest cognitive decline and reached the 240-week PACC decline of the overall cohort 83 weeks earlier. Participants with neither marker showed minimal decline. Dual enrichment reduced sample-size estimates for a clinical trial from 3,252 to 818 participants per arm (75 % reduction). These individuals also demonstrated faster increases in plasma pTau217 and neocortical tau PET. Conclusions A brief DMA combined with plasma pTau217 identifies a subset of cognitively unimpaired, amyloid-positive older adults at highest risk for cognitive and biomarker progression. This dual-marker enrichment strategy enables smaller, shorter, and more cost-efficient preclinical AD trials and supports more targeted evaluation of preventive therapies.
Key findings
- Results Participants with both elevated pTau217 and low DMA exhibited the greatest cognitive decline and reached the 240-week PACC decline of the overall cohort 83 weeks earlier.
- These individuals also demonstrated faster increases in plasma pTau217 and neocortical tau PET.
Why it matters
This analysis of data from the A4 Study found that cognitively unimpaired, amyloid-positive older adults with both elevated plasma pTau217 and low digital memory scores declined faster and could be identified earlier. This enrichment approach could make preclinical Alzheimer's trials more efficient, but it is about trial design, not a treatment for patients.
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Study details
- Participants818
- Evidence strengthHigh
How this study scored 64/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The journal of prevention of Alzheimer's disease) |
| Journal's citation record | 0 / 4 | The Journal of Prevention of Alzheimer s Disease: journal h-index 63 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 818 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 5 / 6 | Cited 23.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Craig E.L. Stark: h-index 62 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of California, Irvine: institution h-index 1,195 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41653883) |
| Free to read | 2 / 2 | Free to read |
| Total | 64 / 100 | — |
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Read the original
- DOI: 10.1016/j.tjpad.2026.100503
- PubMed: 41653883
- Original source →
- Free full text: The Journal of Prevention of Alzheimer s Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Vanderlip, C. R., Gillen, D. L., Grill, J. D., & Stark, C. E. L. (2026). Digital memory assessments and plasma pTau217 enable efficient preclinical Alzheimer's trials. The journal of prevention of Alzheimer's disease. https://doi.org/10.1016/j.tjpad.2026.100503
Vancouver
Vanderlip CR, Gillen DL, Grill JD, Stark CEL. Digital memory assessments and plasma pTau217 enable efficient preclinical Alzheimer's trials. The journal of prevention of Alzheimer's disease. 2026. doi:10.1016/j.tjpad.2026.100503. PMID: 41653883.
BibTeX
@article{vanderlip2026-41653883,
author = {Vanderlip, C. R. and Gillen, D. L. and Grill, J. D. and Stark, C. E. L.},
title = {{Digital memory assessments and plasma pTau217 enable efficient preclinical Alzheimer's trials}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2026},
doi = {10.1016/j.tjpad.2026.100503},
pmid = {41653883},
url = {https://doi.org/10.1016/j.tjpad.2026.100503}
}
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