Platelet count polygenic scores may modify the effect of aspirin in primary prevention of dementia
In brief
Aspirin lowered dementia risk 72% in high platelet-score subgroup, but doubled bleeding
In an analysis of 13,541 older adults in the ASPREE trial, those in the highest fifth of a platelet-count genetic score assigned aspirin had about 72% lower dementia risk than those assigned placebo. Major bleeding was also more than twice as likely. This exploratory genetic subgroup finding needs independent validation before it can guide prevention.
- Journal
- Alzheimer's & dementia : the journal of the Alzheimer's Association (Q1)
- Published
- 1 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Peter D Fransquet, Chenglong Yu, Cammie Tran, Sultana Monira Hussain, Amy Brodtmann, Andrew M Tonkin, et al.
- PMID
- 42781890
- DOI
- 10.1002/alz.71817
Why clinicians should know about it
- Picked for Genetics (clinical) (top studies of the week, 25 October 2026): Platelet‑count polygenic scores modify aspirin effect
Abstract
INTRODUCTION: Aspirin is not recommended for dementia prevention due to limited benefit. We investigated whether genetic subgroups may benefit. METHODS: In the ASPirin in Reducing Events in the Elderly (ASPREE) trial (n = 13,541), we screened 5182 polygenic risk scores (PGSs) for aspirin interactions on dementia and major bleeding. After quality control, 1848 PGSs were analyzed using Cox models for aspirin×PGS interaction, adjusted for age, sex, apolipoprotein Estatus, and ancestry. Interactions were Bonferroni-corrected and examined by quintiles. RESULTS: Platelet-related PGS accounted for 18/112 nominally significant interactions (enrichment_OR = 54.7, p = 3.1 × 10- 1 8). Three highly correlated platelet-count PGSs passed multiple testing. For participants in the highest quintile of the platelet-count PGS003548, aspirin allocation was associated with a 3.5-fold reduction in incident dementia versus placebo (hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.15 to 0.52). Major bleeding was also increased (HR: 2.13, 95% CI: 1.36 to 3.34). Similar interactions were observed using the highest PGS003548 tertile, decile, and 5%. DISCUSSION: Platelet count-related genetic variation may modify aspirin effects on dementia. These hypothesis-generating findings require validation.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.