Self-reported sleep quality and longitudinal amyloid burden in clinically unimpaired adults from the AMYPAD PNHS study

Poor self-reported sleep quality is associated with cognitive impairment. Alzheimer’s disease (AD) patients present sleep disruptions decades before they start to decline clinically. Similarly, amyloid-β (Aβ) starts accumulating during the preclinical phase of the disease. This study investigated associations between self-reported sleep quality and Aβ burden longitudinally in clinically unimpaired (CU) adults. Four hundred seventeen CU adults from the AMYPAD PNHS cohort were included, with baseline self-reported sleep quality assessments (Pittsburgh Sleep Quality Index, PSQI) and longitudinal Aβ PET scans. Participants were categorized by baseline Aβ levels as negative (A-), grey-zone (GZ), or positive (A+). Linear mixed-effects (LME) models tested the association between baseline sleep quality and Aβ burden over time, including interaction effects with baseline Aβ status. Global PSQI score was not associated with Aβ burden over time in the entire group. However, a significant interaction with baseline Aβ status was found, whereby poorer subjective sleep quality was linked to accelerated Aβ accumulation in GZ participants. Poorer subjective sleep quality is associated with faster Aβ accumulation in CU individuals with intermediate Aβ levels, highlighting sleep as a potential target for early AD prevention and identifying an optimal intervention window.