Associations of sleep disorders with serum neurofilament light chain levels in Parkinson's disease.

BACKGROUND: Sleep disorders are a prevalent non-motor symptom of Parkinson's disease (PD), although reliable biological markers are presently lacking. OBJECTIVES: To explore the associations between sleep disorders and serum neurofilament light chain (NfL) levels in individuals with prodromal and early PD. METHODS: The study contained 1113 participants, including 585 early PD individuals, 353 prodromal PD individuals, and 175 healthy controls (HCs). The correlations between sleep disorders (including rapid eye movement sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS)) and serum NfL levels were researched using multiple linear regression models and linear mixed-effects models. We further investigated the correlations between the rates of changes in daytime sleepiness and serum NfL levels using multiple linear regression models. RESULTS: In baseline analysis, early and prodromal PD individuals who manifested specific behaviors of RBD showed significantly higher levels of serum NfL. Specifically, early PD individuals who experienced nocturnal dream behaviors (ß = 0.033; P = 0.042) and movements of arms or legs during sleep (ß = 0.027; P = 0.049) showed significantly higher serum NfL levels. For prodromal PD individuals, serum NfL levels were significantly higher in individuals suffering from disturbed sleep (ß = 0.038; P = 0.026). Our longitudinal findings support these baseline associations. Serum NfL levels showed an upward trend in early PD individuals who had a higher total RBDSQ score (ß = 0.002; P = 0.011) or who were considered as probable RBD (ß = 0.012; P = 0.009) or who exhibited behaviors on several sub-items of the RBDSQ. In addition, early PD individuals who had a high total ESS score (ß = 0.001; P = 0.012) or who were regarded to have EDS (ß = 0.013; P = 0.007) or who exhibited daytime sleepiness in several conditions had a trend toward higher serum NfL levels. CONCLUSION: Sleep disorders correlate with higher serum NfL, suggesting a link to PD neuronal damage. Early identification of sleep disorders and NfL monitoring are pivotal in detecting at-risk PD patients promptly, allowing for timely intervention. Regular monitoring of NfL levels holds promise for tracking both sleep disorders and disease progression, potentially emerging as a biomarker for evaluating treatment outcomes.

Amyloid Pathology Modulates the Associations of Neuropsychiatric Symptoms with Cognitive Impairments and Neurodegeneration in Non-Demented Elderly.

BACKGROUND: The associations between neuropsychiatric symptoms (NPSs) and Alzheimer's disease (AD) have been well-studied, yet gaps remain. OBJECTIVE: We aimed to examine the associations of four subsyndromes (hyperactivity, psychosis, affective symptoms, and apathy) of NPSs with cognition, neurodegeneration, and AD pathologies. METHODS: Totally 1,040 non-demented elderly (48.07% males) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were included. We assessed the relationships between NPSs and AD neuropathologies, cognition, neurodegeneration, and clinical correlates in cross-sectional and longitudinal via multiple linear regression, linear mixed effects, and Cox proportional hazard models. Causal mediation analyses were conducted to explore the mediation effects of AD pathologies on cognition and neurodegeneration. RESULTS: We found that individuals with hyperactivity, psychosis, affective symptoms, or apathy displayed a poorer cognitive status, a lower CSF amyloid-ß (Aß) level and a higher risk of clinical conversion (p < 0.05). Hyperactivity and affective symptoms were associated with increasing cerebral Aß deposition (p < 0.05). Except psychosis, the other three subsyndromes accompanied with faster atrophy of hippocampal volume (p < 0.05). Specific NPSs were predominantly associated with different cognitive domains decline through an 8-year follow-up (p < 0.05). Moreover, the relationships between NPSs and cognitive decline, neurodegeneration might be associated with Aß, the mediation percentage varied from 6.05% to 17.51% (p < 0.05). CONCLUSIONS: NPSs could be strongly associated with AD. The influences of NPSs on cognitive impairments, neurodegeneration might be partially associated with Aß.