Altered glymphatic enhancement of cerebrospinal fluid tracer in individuals with chronic poor sleep quality

Chronic sleep disturbance is a risk factor for dementia disease, possibly due to impaired sleep-dependent clearance of toxic metabolic by-products. We compared enrichment of a cerebrospinal fluid (CSF) tracer within brain of patients reporting good or poor sleep quality, assessed by the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Tracer enrichment in a selection of brain regions was assessed using multiphase magnetic resonance imaging up to 48 hours after intrathecal administration of the contrast agent gadobutrol (0.5 ml of 1 mmol/ml) serving as tracer. Tracer enrichment differed between patients with good (PSQI <= 5) and poor (PSQI >5) sleep quality in a cohort of non-dementia individuals (n = 44; age 42.3 +/- 14.5 years), and in patients with the dementia subtype idiopathic normal pressure hydrocephalus (n = 24; age 71.0 +/- 4.9 years). Sleep impairment was associated with increased CSF tracer enrichment in several brain regions. Cortical brain volume as well as entorhinal cortex thickness was reduced in the oldest cohort and was correlated with the severity of sleep disturbance and the degree of cortical tracer enrichment. We suggest chronic sleep disturbance is accompanied by altered glymphatic function along enlarged perivascular spaces.

Automated summary

Chronic sleep disturbance is associated with impaired clearance of metabolic by-products in the brain, increasing the risk of dementia disease. Using the Pittsburgh Sleep Quality Index questionnaire, we compared tracer enrichment in the brain of patients with good or poor sleep quality using magnetic resonance imaging. The results showed that sleep impairment was correlated with increased tracer enrichment in multiple brain regions, as well as reduced brain volume and cortex thickness. We suggest that chronic sleep disturbance may be related to impaired glymphatic function in the brain.