The associations of cerebrospinal fluid biomarkers with cognition, and rapid eye movement sleep behavior disorder in early Parkinson's disease

BackgroundIn Parkinson's disease (PD), levels of cerebrospinal fluid (CSF) biomarkers and progression of non-motor symptoms are associated, but the specifics are not yet clear. ObjectiveThe aim of this study was to investigate the associations of non-motor symptoms with CSF biomarkers in PD. Materials and methodsWe assessed 487 individuals from the Parkinson's Progression Markers Initiative (PPMI), consisting of 155 healthy controls (HCs) and 332 individuals with PD. Patients with PD were grouped according to non-motor symptoms and compared CSF alpha-synuclein (alpha-syn), amyloid-beta 1-42 (A beta(1-42)), and total tau (t-tau) levels. Multiple linear regressions were used in baseline analysis and linear mixed-effects models in longitudinal analysis. Analyses of mediating effects between cognition and CSF biomarkers were also performed. ResultsAt baseline, PD patients with cognitive impairment (PDCI) exhibited significantly lower CSF alpha-syn (beta = -0.1244; P = 0.0469), A beta (beta = -0.1302; P = 0.0447), and t-tau (beta = -0.1260; P = 0.0131) levels than PD patients without cognitive impairment (PDCU). Moreover, a faster decline of alpha-syn (beta = -0.2152; P = 0.0374) and A beta (beta = -0.3114; P = 0.0023) and a faster rise of t-tau (beta = -0.1534; P = 0.0274) have been found in longitudinal analysis. The A beta positive group showed an earlier decline in cognitive performance (beta = -0.5341; P = 0.0180) compared with the negative A beta group in both analyses. In addition, we found that PD patients with probable rapid eye movement sleep behavior disorder (pRBD) showed decreased CSF alpha-syn (beta = -0.1343; P = 0.0033) levels. Finally, mediation analysis demonstrated that olfactory function partially mediated the relationship between cognition and CSF biomarkers levels. ConclusionOur study shows that CSF biomarkers are associated with cognition at baseline and longitudinally. Cognitive impairment is more severe in patients with a heavier A beta burden. CSF alpha-syn decreased in PD patients with pRBD. This study suggests that early recognition of the increased risk of non-motor symptoms is important for disease surveillance and may be associated with the pathological progression of CSF markers.