Overnight Change in Nfl is Related to Sleep Quality in Parkinson’s Disease
Caileigh Dintino1, Theresa Swift-Scanlan2, Unsong Oh1, Nitai Mukhopadhyay3, Elizabeth Crump1, Ronnie Hayes4, Erika Shelton5, Samantha Holden5, Josiane Broussard6, Matthew Barrett1, Sarah Lageman1, Brian Berman1
1Neurology, 2School of Nursing, 3Biostatistics, Virginia Commonwealth University, 4Virginia Commonwealth University, 5Neurology, University of Colorado, 6Health and Exercise Science, Colorado State University
Objective:
Evaluate the relationship between sleep and overnight changes in neurofilament light chain (NfL) in individuals with Parkinson’s disease (PD) compared to healthy controls (HC).
Background:
NfL may have utility as a biomarker of neurodegeneration in PD.1,2 The glymphatic system, which is most active during sleep, clears NfL from the brain.3 Sleep disturbances in PD likely contribute to disease progression,4-9 but the relationship between NfL levels and sleep in PD has not been characterized.
Design/Methods:
PD participants and HC aged 50-80y underwent an overnight polysomnogram with blood draws at 8:00pm (PM) and 6:00am (AM). Plasma NfL concentration was estimated in pg/mL using Meso Scale Discovery R-plex
assays. T-tests were used to compare PM vs AM NfL levels and differences in changes between groups. Correlations were tested with Pearson coefficients. Significance was defined as p<0.05.
Results:
Forty PD participants (22M/19F, 67.3±5.6y) and 15 HC (6M/9F, 63.5±8.2y) were enrolled. PD participants had reduced sleep efficiency (66.9±15.9% vs 76.5±12.8%; p=0.041) and increased wake after sleep onset (WASO, 114.0±59.1 minutes vs 73.6±51.5 minutes; p=0.023) compared to HC. There was an 8% increase in NfL from PM to AM in PD (PM: 76.2.9±54.5, AM: 81.9±59.3; p=0.037) while no increase was seen in HC (p=0.996). In PD, %change in NfL was negatively correlated with
total sleep time (r=-0.50, p=0.002), sleep efficiency (r=-0.47, p=0.003), and time in NREM and REM (r=-0.39, p=0.003 and r=-0.33, p=0.046respectively), and positively with WASO (r=0.52, p=0.001). In HC, %change in NfL was negatively correlated with time in NREM (r=-0.58, p=0.027).
Conclusions:
Impaired sleep in PD is associated with overnight increases in plasma Nfl, suggesting that changes in plasma NfL could serve as a biomarker of sleep quality. Further research is needed to determine if disruptions in glymphatic system activity are responsible for the overnight changes in NfL seen in PD.
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