Glymphatic Dysfunction Across Sleep Disorders and Its Cognitive Implications

Sleep disorders such as obstructive sleep apnea (OSA), sleep deprivation (SD), and narcolepsy type 1 (NT1), are associated with cognitive dysfunction and an increased risk of neurodegenerative disease. Glymphatic transport disruption has been suggested as one potential mechanistic link. However, evidence across sleep disorders and glymphatic-related metrics remains fragmented. We aimed to determine whether glymphatic-related metrics are altered in OSA, SD, and NT1. We performed a systematic review and meta-analysis of clinical and preclinical studies to determine whether glymphatic-related metrics are altered in OSA, SD, and NT1. Across studies of OSA, glymphatic-related metrics indicated significant impairment of glymphatic transport with a moderate negative association between apnea-hypopnea index (AHI) and diffusion tensor imaging along the perivascular space (DTI-ALPS) index (r=-0.53, 95% confidence interval (CI): -0.63 to -0.41; p<0.001). Available evidence did not demonstrate statistically significant alterations in glymphatic measures in SD or NT1. These findings suggest that impaired glymphatic transport may represent a potential pathway linking OSA to cognitive decline and neurodegenerative risk. However, current evidence is insufficient to determine whether comparable alterations occur in SD or NT1. Substantial heterogeneity across studies highlights the need for standardized reporting and harmonized methodologies to advance the field.