Association between sleep duration and fluid biomarkers of Alzheimer's disease: A systematic review

This systematic review (PROSPERO CRD420246206360) investigated relationships between self-reported or objective sleep duration and fluid biomarkers of Alzheimer's disease pathology and neurodegeneration: cerebrospinal fluid or blood Aβ, p-tau181, t-tau, NfL and GFAP. We searched PubMed, SCOPUS, and CINAHL from inception to September 2024. Twenty studies (n = 12,445) met inclusion criteria (13 cerebrospinal fluid biomarkers [n = 2836]; 7 blood biomarkers [n = 9609]). Study quality was assessed using Newcastle-Ottawa scales. Whereas many studies did not report any associations, some trends emerged: short sleep duration was associated with higher cerebrospinal fluid t-tau and p-tau181 and lower cerebrospinal fluid or blood Aβ42 across multiple studies. Longer sleep duration showed more variable associations, with some suggesting either worse or better biomarker profiles (e.g., higher and lower fluid t-tau, p-tau181, or Aβ42). Two studies investigating non-linear relationships identified U-shaped associations, suggesting both short (≤5-6 h) and long (≥8 h) sleep durations are associated with altered biomarker profiles. The predominantly cross-sectional and high heterogeneity of the available evidence, as well as the relatively small number of studies by individual biomarker (especially for NfL and GFAP) limit conclusions about sleep-biomarker relationships. Future research should investigate emerging blood-based biomarkers and explore temporal associations between sleep duration and Alzheimer's disease biomarker changes.