Associations of sleep disorders with cerebrospinal fluid α-synuclein in prodromal and early Parkinson's disease

Abstract

Objectives: Our aim is to investigate the associations of sleep disorders with cerebrospinal fluid (CSF) α-synuclein (α-syn) in healthy controls (HCs), and patients with prodromal and early Parkinson's disease (PD).

Methods: We included a total of 575 individuals, consisting of 360 PD individuals, 46 prodromal PD individuals, and 169 HCs. Multiple linear regression models and linear mixed-effects models were used to investigate the associations of sleep disorders with baseline and longitudinal CSF α-syn. Associations between the change rates of sleep disorders and CSF α-syn were further investigated via multiple linear regression models.

Results: In PD, probable Rapid-eye-movement sleep Behavior Disorder (pRBD) (β = - 0.1199; P = 0.0444) and RBD sub-items, such as aggressive dreams (β = - 0.1652; P = 0.0072) and hurting bed partner (β = - 0.2468; P = 0.0010), contributed to lower CSF α-syn. The association between aggressive dreams and lower CSF α-syn further survived Bonferroni correction (P < 0.0036). In prodromal PD, dream-enacting (a specific RBD behavior) was significantly associated with decreased CSF α-syn during the follow-up (β = - 0.0124; P = 0.0237). HCs with daytime sleepiness when inactive-sitting in public places (β = - 0.0033; P = 0.0135) showed decreased CSF α-syn. Furthermore, increased possibilities of daytime sleepiness when sitting and reading contributed to a greater decrease of CSF α-syn in HCs (β = - 196.8779; P = 0.0433).

Conclusions: Sleep disorders were associated with decreased CSF α-syn. Sleep management may be important for disease monitoring and preventing the progression of α-syn pathology.

Keywords: Cerebrospinal fluid; Parkinson’s disease; Sleep disorders; α-Synuclein.