2026/06/01 by Meng-Yao Li, Ying-Ni Lin, Xi-xi Chen +8 · 1 voice
Neuroscience · Psychology · Medicine · #Sleep and Wakefulness Research #Sleep and related disorders #Restless Legs Syndrome Research
paper · doi:10.1016/j.lmd.2026.100131
openalex publication_date 2026/06/01 · openalex created_date 2026/06/03 · openalex updated_date 2026/07/22
Sleep disorders, including obstructive sleep apnea (OSA), chronic insomnia, and sleep deprivation, are increasingly linked to dysfunction of the blood-brain barrier (BBB), a key regulator of central nervous system homeostasis. Growing evidence demonstrates that BBB injury is associated with cognitive impairment, including Alzheimer’s disease (AD), white matter injury, cerebral small vessel disease, and vascular cognitive impairment. This review summarizes evidence that disturbed sleep impairs BBB integrity and discusses the underlying mechanisms. BBB injury may increase para-cellular permeability, alter endothelial transport, and impair metabolic clearance pathways, thereby facilitating the entry of circulating toxins into the brain and amplifying glial activation, cerebrovascular dysfunction, and neurodegenerative processes. Furthermore, BBB breakdown in the hippocampus may represent an early marker of cognitive dysfunction, which is partly independent of classical amyloid-β and tau pathology. However, this finding requires further validation in larger, longitudinal cohorts. Finally, we discuss the future of therapeutic strategies aimed at both sleep restoration and BBB-related mechanisms and potential biomarkers for assessing BBB dysfunction. We identify key knowledge gaps, including the lack of validated BBB biomarkers in sleep disorders and limited evidence for reversibility of BBB injury after treatment.