"We calculated a weighted ADHD-PRS in 212 CU individuals without a
clinical diagnosis of ADHD (55–90 years). These individuals had baseline
amyloid-β (Aβ) positron emission tomography, longitudinal cerebrospinal
fluid (CSF) phosphorylated tau at threonine 181 (p-tau181),
magnetic resonance imaging, and cognitive assessments for up to 6 years.
Linear mixed-effects models were used to test the association of
ADHD-PRS with cognition and AD biomarkers. Higher ADHD-PRS was
associated with greater cognitive decline over 6 years. The combined
effect between high ADHD-PRS and brain Aβ deposition on cognitive
deterioration was more significant than each individually. Additionally,
higher ADHD-PRS was associated with increased CSF p-tau181
levels and frontoparietal atrophy in CU Aβ-positive individuals. Our
results suggest that genetic liability for ADHD is associated with
cognitive deterioration and the development of AD pathophysiology.
Findings were mostly observed in Aβ-positive individuals, suggesting
that the genetic liability for ADHD increases susceptibility to the
harmful effects of Aβ pathology."