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Updated: Oct 17, 2026

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Attention-deficit/hyperactivity disorder polygenic risk score and incidence of cognitive impairment in older adults:
Douglas Teixeira Leffa1, Guilherme Bauer-Negrini1, Livia Amaral1
1Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
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.
Related Concept Videos
Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings.
Alzheimer Disease l: Introduction
Cognitive Development During Adulthood
