Evidence map›Paper›PMID 41653883›Full record

Trial reportThe journal of prevention of Alzheimer's disease2026

Digital memory assessments and plasma pTau217 enable efficient preclinical Alzheimer's trials.

Casey R Vanderlip, Daniel L Gillen, Joshua D Grill, Craig E L Stark

Abstract readRandomized Controlled TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The journal of prevention of Alzheimer's disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Remote outcome measures in Alzheimer's disease clinical trials: A call to action.The journal of prevention of Alzheimer's disease · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Casey R VanderlipDepartment of Neurobiology and Behavior, 1424 Biological Sciences III Irvine, University of California Irvine, Irvine, CA, 92697 USA. Electronic address: vanderlc@hs.uci.edu.
Daniel L GillenDepartment of Statistics, University of California Irvine, Irvine, CA, 92697 USA.
Joshua D GrillDepartment of Neurobiology and Behavior, 1424 Biological Sciences III Irvine, University of California Irvine, Irvine, CA, 92697 USA; Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, 92697 USA.
Craig E L StarkDepartment of Neurobiology and Behavior, 1424 Biological Sciences III Irvine, University of California Irvine, Irvine, CA, 92697 USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPreclinical 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.

objectivesTo 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.

designAnalysis 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.

settingSecondary-prevention trial conducted across sites in the United States, Canada, Australia, and Japan.

participantsA 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.

resultsParticipants 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.

conclusionsA 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.

Indexed as

Alzheimer DiseaseMemorytau ProteinsAgedAged, 80 and overBiomarkersDisease ProgressionFemaleHumansMaleNeuropsychological TestsProdromal SymptomsBiomarkersMAPT protein, humantau ProteinsAlzheimer’s diseaseClinical trialsDigital memory assessmentsEarly detectionPreventionpTau217

Identifiers

PMID41653883
PMCPMC12907085

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.