The Prevalence of Sleep Disorders in Populations with Glymphatic Dysfunction: A Systematic Review and Meta-Analysis

The glymphatic system supports metabolic waste clearance during sleep and is essential for brain homeostasis. Disruption of this system has been linked to sleep disorders, yet the overall prevalence of sleep disorders in populations showing impaired glymphatic-related function remains unclear. This systematic review and meta-analysis evaluated the prevalence of sleep disorders in human cohorts with structural, functional, or biochemical imaging markers of impaired glymphatic activity. Following PRISMA guidelines, major databases were searched up to August 2025. Eligible observational studies reported sleep disorder prevalence in populations characterized by enlarged perivascular spaces, white matter hyperintensities, DTI-ALPS (DTI-ALPS: Diffusion tensor image analysis along perivascular space) alterations, ultrafast fMRI (fMRI: functional magnetic resonance) indices, or CSF/PET (CSF: cerebrospinal fluid; PET: positron emission tomography) clearance deficits. Random-effects models generated pooled estimates, and heterogeneity, publication bias, and moderators were examined using I² statistics, Egger's test, trim-and-fill, and meta-regression. Nineteen studies (≈4500 participants) met the inclusion criteria. The pooled prevalence of sleep disorders in populations with impaired glymphatic-related function was 44.9% (95% CI: 34.9-55.3%), with substantial heterogeneity (I² ≈ 95%). Meta-regression identified older age and case-control design as significant contributors, while imaging modality, sex distribution, and sample size were not. Publication bias was minimal. Sleep disorders are common among individuals with impaired glymphatic-related markers, reflecting co-occurrence rather than causality. Standardized longitudinal studies are needed to clarify mechanisms and clinical relevance.