Impaired Sleep is Associated with Tau Deposition on F-flortaucipir PET and Accelerated Cognitive Decline, Accounting for Medications That Affect Sleep

Background: Impaired sleep is commonly associated with Alzheimer's disease (AD), although the underlying mechanisms remain unclear. Furthermore, the moderating effects of sleep-affecting medications, which have been linked to AD pathology, are incompletely characterized. Using data from the Alzheimer's Disease Neuroimaging Initiative, we investigated whether a medical history of impaired sleep, informant-reported nighttime behaviors, and sleep-affecting medications are associated with beta-amyloid and tau deposition on PET and cognitive change, cross-sectionally and longitudinally.

Methods: We included 964 subjects with F-florbetapir PET scans. Measures of sleep impairment and medication use were obtained from medical histories and the Neuropsychiatric Inventory Questionnaire. Multivariate models, adjusted for covariates, were used to assess associations among sleep-related features, beta-amyloid and tau, and cognition. Cortical tau deposition, categorized by Braak stage, was assessed using the standardized uptake value peak alignment (SUVP) method on F-flortaucipir PET.

Results: Medical history of sleep impairment was associated with greater baseline tau in the meta-temporal, Braak 1, and Braak 4 regions (p = 0.04, p < 0.001, p = 0.025, respectively). Abnormal nighttime behaviors were also associated with greater baseline tau in the meta-temporal region (p = 0.024), and greater cognitive impairment, cross-sectionally (p = 0.007) and longitudinally (p < 0.001). Impaired sleep was not associated with baseline beta-amyloid (p > 0.05). Short-term use of selective serotonin reuptake inhibitors and benzodiazepines slightly weakened the sleep-tau relationship.

Conclusions: Sleep impairment was associated with tauopathy and cognitive decline, which could be linked to increased tau secretion from neuronal hyperactivity. Clinically, our results help identify high-risk individuals who could benefit from sleep-related interventions aimed to delay cognitive decline and AD.