Differential effects of sleep on brain structure and metabolism at the preclinical stages of AD

Abstract INTRODUCTION Poor sleep quality is associated with cognitive outcomes in Alzheimer's disease (AD). We analyzed the associations between self‐reported sleep quality and brain structure and function in cognitively unimpaired (CU) individuals. METHODS CU adults ( N = 339) underwent structural magnetic resonance imaging, lumbar puncture, and the Pittsburgh Sleep Quality Index (PSQI) questionnaire. A subset ( N = 295) performed [18F] fluorodeoxyglucose positron emission tomography scans. Voxel‐wise associations with gray matter volumes (GMv) and cerebral glucose metabolism (CMRGlu) were performed including interactions with cerebrospinal fluid (CSF) AD biomarkers status. RESULTS Poorer sleep quality was associated with lower GMv and CMRGlu in the orbitofrontal and cingulate cortices independently of AD pathology. Self‐reported sleep quality interacted with altered core AD CSF biomarkers in brain areas known to be affected in preclinical AD stages. DISCUSSION Poor sleep quality may impact brain structure and function independently from AD pathology. Alternatively, AD‐related neurodegeneration in areas involved in sleep–wake regulation may induce or worsen sleep disturbances. Highlights Poor sleep impacts brain structure and function independent of Alzheimer's disease (AD) pathology. Poor sleep exacerbates brain changes observed in preclinical AD. Sleep is an appealing therapeutic strategy for preventing AD.