Sleep Dysregulation Is Associated with 18 F-FDG PET and Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease

Background: Sleep impairment has been commonly reported in Alzheimer's disease (AD) patients. The association between sleep dysregulation and AD biomarkers has been separately explored in mild cognitive impairment (MCI) and AD patients. Objective: The present study investigated cerebrospinal-fluid (CSF) and 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) biomarkers in MCI and AD patients in order to explore their association with sleep parameters measured with polysomnography (PSG). Methods: MCI and AD patients underwent PSG, 18F-FDG-PET, and CSF analysis for detecting and correlating these biomarkers with sleep architecture. Results: Thirty-five patients were included in the study (9 MCI and 26 AD patients). 18F-FDG uptake in left Brodmann area 31 (owing to the posterior cingulate cortex) correlated negatively with REM sleep latency (p = 0.013) and positively with REM sleep (p = 0.033). 18F-FDG uptake in the hippocampus was negatively associated with sleep onset latency (p = 0.041). Higher CSF orexin levels were associated with higher sleep onset latency (p = 0.042), Non-REM stage 1 of sleep (p = 0.031), wake after sleep onset (p = 0.028), and lower sleep efficiency (p = 0.045). CSF levels of Aβ42 correlated negatively with the wake bouts index (p = 0.002). CSF total-tau and phosphorylated tau levels correlated positively with total sleep time (p = 0.045) and time in bed (p = 0.031), respectively. Conclusion: Sleep impairment, namely sleep fragmentation, REM sleep dysregulation, and difficulty in initiating sleep correlates with AD biomarkers, suggesting an effect of sleep on the pathological processes in different AD stages. Targeting sleep for counteracting the AD pathological processes represents a timely need for clinicians and researchers.