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PreprintCC BY-NDmedRxiv

Glymphatic Dysfunction Across Sleep Disorders and Its Cognitive Implications

  1. 1School of Life Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom

Abstract

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.

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BibTeX
@misc{whitehouse2026glymphatic,
  title = {{Glymphatic Dysfunction Across Sleep Disorders and Its Cognitive Implications}},
  author = {R. M. Whitehouse and T. D. Farr and S. Li and R. Huckstepp and J. Boltze},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.20.26366043},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.20.26366043v1},
  note = {CC BY-ND},
}
RIS
TY  - UNPB
TI  - Glymphatic Dysfunction Across Sleep Disorders and Its Cognitive Implications
AU  - R. M. Whitehouse
AU  - T. D. Farr
AU  - S. Li
AU  - R. Huckstepp
AU  - J. Boltze
PY  - 2026
DA  - 2026/10/20
PB  - medRxiv
DO  - 10.64898/2026.10.20.26366043
UR  - https://www.medrxiv.org/content/10.64898/2026.10.20.26366043v1
AB  - 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.
ER  -