Longitudinal evolution and plasma biomarkers for excessive daytime sleepiness in Parkinson's disease

Abstract Background Excessive daytime sleepiness (EDS) is one of the most frequent non-motor symptoms in Parkinson's disease (PD); however, the pathogenesis of EDS is unclear, and there is a lack of information on plasma biomarkers for EDS in PD. We aimed to investigate the plasma biomarkers of EDS in a large PD cohort. Methods A total of 159 PD patients were included in the prospective cohort study and followed up annually for three years. Plasma biomarkers including glial fibrillary acidic protein, amyloid-beta, p-tau181, and neurofilament light chain (NfL), were measured using an ultrasensitive single-molecule array (SimoaTM) technology at each visit. EDS was evaluated using the Epworth Sleepiness Scale (ESS). Results The frequency of EDS in PD increased from 15.1% at baseline to 25.0% after three years. The mean ESS scores increased from 5.1 [Standard Deviation (SD): 4.8] at baseline to 6.1 [SD: 5.5] at the third year of follow-up. At baseline, compared with patients with PD without EDS, those with EDS were more likely to be male, had poorer cognitive performance, and more severe motor and non-motor symptoms. The adjusted generalized estimating equations models showed that higher plasma NfL levels (OR 1.047 [1.002-1.094], p = 0.042) were associated with EDS during follow-ups. The adjusted linear mixed-effects model showed that higher plasma NfL levels (β 0.097 [0.012–0.183], p = 0.026) were associated with ESS scores during follow-ups. Conclusions Higher plasma NfL levels were associated with EDS in PD, indicating an association between neuro-axonal degeneration and EDS in PD.