BACKGROUND AND AIMS
The most prevalent neurodegenerative diseases (NDD) are Alzheimer’s disease and Parkinson’s disease, affecting 43.3 and 6.1 million individuals globally, respectively.1,2 Altered sleep is present early in NDDs, and may contribute to neurodegeneration. However, much of the evidence on the association between sleep changes and incident NDDs comes from self-reports and actigraphy data, which lack objective measures of sleep structure. Long-term, large sample size studies assessing the association between NDDs and objective polysomnography-based sleep features are scant. The aim of this study was to investigate whether objective sleep features are associated with long-term incidence of NDDs.
MATERIALS AND METHODS
This retrospective cohort study included polysomnographic data of patients referred to the Sleep Disorders Unit, Department of Neurology, Medical University Innsbruck, Austria, from January 2004–December 2007. All patients ≥18 years undergoing polysomnography and without NDDs at baseline or within 5 years were included. Main outcome was a diagnosis of NDDs at least 5 years after polysomnography, assessed until December 2021.
Of the 1,454 patients assessed for eligibility, 999 (68.7%) met inclusion criteria (683 [68.3%] male; median age 54.9 years [interquartile range: 33.9–62.7]). In total, 75 patients (7.5%) developed NDDs and 924 (92.5%) remained disease-free after a median follow-up of 12.8 years (interquartile range: 9.9–14.6). After adjusting for several demographic, sleep, and clinical covariates, 1% decrease in sleep efficiency, N3 sleep, or rapid eye movement (REM) sleep was associated with 1.9%, 6.5%, or 5.2% increased risk of incident neurodegeneration, respectively (hazard ratio [HR]: 1.019; 95% confidence interval [CI]: 1.002–1.035; HR: 1.065; 95% CI: 1.007–1.118; HR: 1.052; 95% CI: 1.012–1.085, respectively). Further, 1.0% decrease in wake within sleep period time (SPT) represented a 2.2% reduced risk of incident NDDs (HR: 0.978; CI: 0.958-0.997). Patients with the highest quartile of wake in SPT (>18.6%), or the lowest quartile of REM sleep (<13.0%) or N3 sleep (0%), had the shortest overall mean disease-free survival time (14.9; CI: 14.6–15.3 years).
In this cohort, an altered sleep architecture at baseline with reduced sleep efficiency, REM sleep, or N3 sleep, or increased wake in SPT, was associated with incident neurodegeneration after 5 or more years. These findings support the hypothesis that sleep changes may contribute to NDDs’ pathogenesis, and point to sleep as an early marker of neurodegeneration and a potential target of neuroprotective strategies. To put it into perspective, consider the analogy of a balanced diet.
We understand that it is not just about the total amount of calories we consume, but the balance and diversity of nutrients, such as proteins, carbohydrates, fats, vitamins, and minerals. Similarly, it is not just the total number of hours that we sleep that matters, but the specific stages and quality of sleep we experience.