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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-026-02049-w.