- Higher ADHD-PRS predicts greater risk of incident cognitive impairment in older adults, with 10-year cumulative incidence 33.8% highest tertile versus 23.4% lowest.
- Association remains significant after adjustment for education, APOE ε4 status and vascular risk factors.
- Polygenic risk scores for other psychiatric disorders showed no association; ADHD-PRS link was not modified by baseline amyloid-β status.
Alzheimers Dement. 2026 Oct;22(10):e71770. doi: 10.1002/alz.71770.
ABSTRACT
INTRODUCTION: Preliminary evidence suggests a link between attention-deficit/hyperactivity disorder (ADHD) and later-life cognitive impairment. Whether genetic risk for ADHD, estimated using an ADHD polygenic risk score (ADHD-PRS), is associated with incident cognitive impairment (mild cognitive impairment or Alzheimer’s disease dementia) remains unknown.
METHODS: We analyzed 7761 cognitively unimpaired (CU) older adults with whole-genome sequencing from eight cohorts participating in the Alzheimer’s Disease Sequencing Project (ADSP).
RESULTS: During follow-up, 1347 participants developed cognitive impairment. Ten-year cumulative incidence was 33.8% in the highest ADHD-PRS tertile versus 23.4% in the lowest. In Cox models, higher ADHD-PRS remained associated with greater risk of cognitive impairment after adjustment for education, apolipoprotein E (APOE) ε4 status, or vascular risk. PRSs for other major psychiatric disorders were not associated with cognitive impairment in the same analytic framework. In a subsample with biomarker data, the association was not modified by baseline amyloid-β status.
DISCUSSION: These findings support ADHD-PRS as a novel correlate of cognitive impairment and vulnerability in aging.
PMID:42878194 | DOI:10.1002/alz.71770
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