Platelet-count genetic scores identify ASPREE subgroup with 70% lower dementia incidence on low-dose aspirin
A post-hoc genetic stratification of the ASPREE randomized trial found a platelet-count polygenic score that marks older adults who experienced a 70% relative reduction in dementia with low-dose aspirin, accompanied by doubled major-bleeding rates. The signal points to platelet biology rather than canonical Alzheimer pathways. Targeted replication trials are required before any genotype-guided recommendation.
The Monash-led analysis stratified participants by polygenic scores derived from platelet-count GWAS loci and compared dementia and major-bleeding outcomes within the randomized aspirin-versus-placebo arms. The benefit was confined to the highest-score quintile; no signal appeared for established Alzheimer risk loci such as APOE. Absolute bleeding risk rose from 2.1% to 4.4% in the same subgroup, illustrating the classic aspirin trade-off. Because the interaction was identified post-randomization, the finding remains hypothesis-generating despite the trial's overall null result on dementia.
Fransquet et al.: A genotype-stratified RCT powered at 80% will report >50% dementia-risk reduction with aspirin in the high platelet-score arm by 2031.
Sources (2)
- [1]Primary Source(https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70012)
- [2]Supporting Source(https://www.nejm.org/doi/10.1056/NEJMoa1800722)