Reduced Regional NREM Sleep Slow-Wave Activity Is Associated With Cognitive Impairment in Parkinson Disease

Simon J Schreiner,Lukas L Imbach,Philipp O Valko,Esther Werth,Heide Baumann-Vogel,Christian R Baumann,Rina Maqkaj,Angelina Maric

doi:10.3389/fneur.2021.618101

Simon J Schreiner, Lukas L Imbach + Show 6 more

Open Access

https://doi.org/10.3389/fneur.2021.618101

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Abstract

Growing evidence implicates a distinct role of disturbed slow-wave sleep in neurodegenerative diseases. Reduced non-rapid eye movement (NREM) sleep slow-wave activity (SWA), a marker of slow-wave sleep intensity, has been linked with age-related cognitive impairment and Alzheimer disease pathology. However, it remains debated if SWA is associated with cognition in Parkinson disease (PD). Here, we investigated the relationship of regional SWA with cognitive performance in PD. In the present study, 140 non-demented PD patients underwent polysomnography and were administered the Montréal Cognitive Assessment (MoCA) to screen for cognitive impairment. We performed spectral analysis of frontal, central, and occipital sleep electroencephalography (EEG) derivations to measure SWA, and spectral power in other frequency bands, which we compared to cognition using linear mixed models. We found that worse MoCA performance was associated with reduced 1–4 Hz SWA in a region-dependent manner (F2, 687 =11.67, p < 0.001). This effect was driven by reduced regional SWA in the lower delta frequencies, with a strong association of worse MoCA performance with reduced 1–2 Hz SWA (F2, 687 =18.0, p < 0.001). The association of MoCA with 1–2 Hz SWA (and 1–4 Hz SWA) followed an antero-posterior gradient, with strongest, weaker, and absent associations over frontal (rho = 0.33, p < 0.001), central (rho = 0.28, p < 0.001), and occipital derivations, respectively. Our study shows that cognitive impairment in PD is associated with reduced NREM sleep SWA, predominantly in lower delta frequencies (1–2 Hz) and over frontal regions. This finding suggests a potential role of reduced frontal slow-wave sleep intensity in cognitive impairment in PD.

Highlights

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease (AD)
Cognitive impairment as indicated by worse Montréal Cognitive Assessment (MoCA) performance was associated with reduced regional 1–4 Hz Slow-wave activity (SWA) (MoCA∗region: F2, 687 = 11.67, p-corrected < 0.001)
Main effects of MoCA were not significant, indicating that cognition was associated with non-rapid eye movement (NREM) sleep EEG power in a region-dependent manner

Summary

Introduction

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease (AD). Slow-wave sleep (SWS), i.e., deep non-rapid eye movement (NREM) sleep, supports cognition and could modulate neurodegeneration by influencing pathological proteins such as alpha-synuclein, tau, and beta-amyloid [2,3,4]. Sleep induction decreases whereas sleep restriction increases pathological proteins in rodent brain tissue and interstitial fluid and human cerebrospinal fluid [2,3,4]. These dynamics may depend on SWS, as SWS disruption—but not partial sleep restriction with preserved SWS—modulates beta-amyloid levels in humans [5, 6]. SWA likely indicates how strongly SWS could modulate neurodegeneration, as SWA correlates positively with glymphatic clearance in mice [7], and negatively with AD-related cognitive impairment and pathology in humans [8,9,10,11]

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