SLEEP QUALITY AND CEREBROSPINAL FLUID OXYSTEROLS IN DEGENERATIVE DEMENTIAS: CORRELATIONS AND POSSIBLE BIOMEDICAL IMPLICATIONS

Abstract

Objective. The combination and tentative correlation of a selected set of polysomnographic tests with the quantitative measurement of oxysterols of pathophysiological relevance in the cerebrospinal fluid (CF) of patients with Alzheimer’s (AD), non-Alzheimer’s (NAD) degenerative dementia and non-degenerative disorders (C) was afforded in a pilot study. Methods. Sleep efficiency, percentage of sleep time spent in NREM stage 3 (N3), apnoea/hypopnea index, sleep time spent with oxygen saturation < 90% were recorded. Oxysterols of both enzymatic and non-enzymatic origin were quantified in the CSF of the three groups of patients by isotope-dilution gas-chromatography mass-spectrometry. Results. A remarkable increase of all tested oxysterols of autoxidation origin, and of cholesterol as well, was detectable in the CSF of AD and NAD patients in comparison to C. Of the four markers of sleep quality tested, only the percent duration of N3 showed a net progressive reduction in NAD and AD patients. A strong inverse correlation between the CSF levels of 7k-cholesterol and of 7α-hydroxycholesterol and the duration of % N3 in the recruited cohorts of patients appeared evident. Conclusions. The lower was the % duration of N3 sleep, the higher was the accumulation of some oxysterols of autoxidation origin in the CSF of patients, with the highest levels of the latter compounds in AD patients, at least in part due to an impaired efficiency of the glymphatic system, which reaches its maximum in N3, without excluding a yet undisclosed role of altered cholesterol metabolism on sleep quality. Significance. Oxysterols of non-enzymatic origin are proposed as new CSF candidate markers of sleep quality in patients with dementia.