Surrogates of glymphatic metrics decline and coupled sleep rhythms disruption in Alzheimer’s disease

Abstract Background Sleep is essential for brain homeostasis, in part by supporting glymphatic clearance through sleep-related oscillations. However, the relationship between putative glymphatic metrics and coupled sleep rhythm disruption, and their combined role in Alzheimer’s disease (AD) progression, remains poorly understood. Methods We analyzed data from 75 individuals, 54 with AD and 21 cognitively normal (CN) controls, including sleep electroencephalography (EEG), magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) AD biomarkers, and two-year longitudinal cognitive assessments. Putative glymphatic metrics was evaluated using choroid plexus (CP) volume, perivascular spaces (PVSs), diffusion tensor imaging along the perivascular space (DTI-ALPS) index, and blood oxygen level-dependent signal coupled to CSF signal (BOLD-CSF coupling). Coupled sleep rhythm was assessed via slow oscillation (SO)-theta and SO-spindle couplings. Correlation and mediation analyses explored associations between these MRI-derived indices and coupled sleep oscillations, and least absolute shrinkage and selection operator (LASSO) regression was used to predict AD progression. Results Compared to CN controls, individuals with AD had reduced DTI-ALPS index and BOLD-CSF coupling (p