AUTHOR=Tao Mingzhu , Dou Kaixin , Xie Yijie , Hou Binghui , Xie Anmu 

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

JOURNAL=Frontiers in Neuroscience

VOLUME=16

YEAR=2022

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.1049118

DOI=10.3389/fnins.2022.1049118

ISSN=1662-453X

ABSTRACT=<sec><title>Background</title><p>In 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.</p></sec><sec><title>Objective</title><p>The aim of this study was to investigate the associations of non-motor symptoms with CSF biomarkers in PD.</p></sec><sec><title>Materials and methods</title><p>We 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 α-synuclein (α-syn), amyloid-beta 1-42 (Aβ<sub>1–42</sub>), 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.</p></sec><sec><title>Results</title><p>At baseline, PD patients with cognitive impairment (PDCI) exhibited significantly lower CSF α-syn (β = −0.1244; <italic>P</italic> = 0.0469), Aβ (β = −0.1302; <italic>P</italic> = 0.0447), and t-tau (β = −0.1260; <italic>P</italic> = 0.0131) levels than PD patients without cognitive impairment (PDCU). Moreover, a faster decline of α-syn (β = −0.2152; <italic>P</italic> = 0.0374) and Aβ (β = −0.3114; <italic>P</italic> = 0.0023) and a faster rise of t-tau (β = −0.1534; <italic>P</italic> = 0.0274) have been found in longitudinal analysis. The Aβ positive group showed an earlier decline in cognitive performance (β = −0.5341; <italic>P</italic> = 0.0180) compared with the negative Aβ group in both analyses. In addition, we found that PD patients with probable rapid eye movement sleep behavior disorder (pRBD) showed decreased CSF α-syn (β = −0.1343; <italic>P</italic> = 0.0033) levels. Finally, mediation analysis demonstrated that olfactory function partially mediated the relationship between cognition and CSF biomarkers levels.</p></sec><sec><title>Conclusion</title><p>Our study shows that CSF biomarkers are associated with cognition at baseline and longitudinally. Cognitive impairment is more severe in patients with a heavier Aβ burden. CSF α-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.</p></sec>