Association Between the Genetic Risk for Attention-Deficit/Hyperactivity Disorder and Cognitive Function in Older Age: The MYHAT Population-Based Study.

OBJECTIVES

Attention-deficit/hyperactivity disorder (ADHD) has been associated with increased risk for dementia, including Alzheimer's disease (AD). Polygenic risk scores for ADHD (ADHD-PRS) reflect the genetic liability for the disorder and have been linked to cognitive decline in selected clinical samples. This study examined associations between ADHD-PRS and cognitive function in older adults from a population-based cohort and tested whether these associations were moderated by plasma biomarkers of AD and related disorders (ADRD).

METHODS

We analyzed data from 1,468 dementia-free participants from the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study, with cognitive assessments across five domains. ADHD-PRS was calculated, and a subset underwent blood draw for the analysis of ADRD biomarkers. We examined cross-sectional and longitudinal associations between ADHD-PRS and cognition using linear regressions and mixed-effects models adjusting for age, sex, and ancestry.

RESULTS

Higher ADHD-PRS was significantly associated with lower visuospatial function in cross-sectional analyses after correction for multiple comparisons. Associations with attention and language were moderated by education, and higher ADHD-PRS was associated with lower performance only among individuals with ≤ high school education. No associations were found between ADHD-PRS and plasma biomarkers, nor did biomarkers modify the relationship between ADHD-PRS and cognition. In longitudinal analyses, no association between ADHD-PRS and cognitive trajectories remained significant after correction for multiple comparisons.

CONCLUSIONS

Overall, ADHD genetic liability appears relevant to cognitive performance in late life, though longitudinal trajectories remain unaffected. In older age, ADHD-PRS seems to negatively impact visuospatial tests, characterized by complex and integrative demands. Educational attainment moderated the associations with attention and language, suggesting a potential buffering effect.