Sleep features and long-term incident neurodegeneration: a polysomnographic study

Abstract

AbstractWhile a growing body of studies suggests a link between sleep disturbances and neurodegenerative diseases’ (NDDs) development, prior studies have been hindered by small sample sizes, short follow-up times and a lack of objective sleep measures.In this cohort study, patients who underwent polysomnography (PSG) at the Innsbruck Sleep Disorders Unit from January 2004 to December 2007, aged ≥18 years, without NDDs at baseline or within five years post PSG, and with at least five years clinical follow-up were included. The main outcome measure was NDDs diagnosis at least five years after polysomnography, assessed until December 2021.Of 1454 patients assessed for eligibility, 999 (68.7%) met inclusion criteria (683 (68.3%) men; median age 54.9 (interquartile range, IQR 33.9-62.7) years. Seventy-five patients (7.5%) developed NDDs, 924 (92.5%) remained disease-free after 12.8 (IQR 9.9-14.6) years median follow-up. After adjusting for demographic, sleep, and clinical covariates, each percent decrease in sleep efficiency, N3 sleep, or REM sleep was associated with 1.9%, 6.5%, and 5.2% increased risk of incident NDDs (hazard ratio, HR, 1.019, CI:1.002-1.035; HR 1.065, CI:1.007-1.118; HR 1.052, CI:1.012-1.085,), respectively whereas one percent decrease in night-time wakefulness represented a 2.2% reduced risk (HR 0.978, CI:0.958-0.997). Random forest analysis identified wake, followed by N3 and REM sleep percentages, as the most important feature associated with NDDs development. Additionally, multiple sleep features combination offered more robust discrimination of incident NDDs compared to single sleep stages.These findings support contribution of sleep architecture changes to NDDs pathogenesis and provide insights into the temporal window during which these changes are detectable, pointing to sleep as early NDDs marker and potential target of neuroprotective strategies.