CSF Biomarkers Reflecting Protein Pathology and Axonal Degeneration Are Associated with Memory, Attentional, and Executive Functioning in Early-Stage Parkinson's Disease.
In early-stage Parkinson's disease (PD), cognitive impairment is common, and a variety of cognitive domains including memory, attention, and executive functioning may be affected. Cerebrospinal fluid (CSF) biomarkers are potential markers of cognitive functioning. We aimed to explore whether CSF α-synuclein species, neurofilament light chain, amyloid-β42, and tau are associated with cognitive performance in early-stage PD patients. CSF levels of total-α-synuclein and phosphorylated-α-synuclein, neurofilament light chain, amyloid-β42, and total-tau and phosphorylated-tau were measured in 26 PD patients (disease duration ≤5 years and Hoehn and Yahr stage 1-2.5). Multivariable linear regression models, adjusted for age, gender, and educational level, were used to assess the relationship between CSF biomarker levels and memory, attention, executive and visuospatial function, and language performance scores. In 26 early-stage PD patients, attention and memory were the most commonly affected domains. A higher CSF phosphorylated-α-synuclein/total-α-synuclein ratio was associated with better executive functioning (sβ = 0.40). Higher CSF neurofilament light was associated with worse memory (sβ = -0.59), attentional (sβ = -0.32), and executive functioning (sβ = -0.35). Reduced CSF amyloid-β42 levels were associated with poorer attentional functioning (sβ = 0.35). Higher CSF phosphorylated-tau was associated with worse language functioning (sβ = -0.33). Thus, CSF biomarker levels, in particular neurofilament light, were related to the most commonly affected cognitive domains in early-stage PD. This indicates that CSF biomarker levels may identify early-stage PD patients who are at an increased risk of developing cognitive impairment.
['Oosterveld|Linda P|LP|', 'Kuiper|Tessa I|TI|', 'Majbour|Nour K|NK|', 'Verberk|Inge M W|IMW|', 'van Dijk|Karin D|KD|', 'Twisk|Jos W R|JWR|', 'El-Agnaf|Omar M|OM|0000-0002-6850-8084', 'Teunissen|Charlotte E|CE|', 'Weinstein|Henry C|HC|', 'Klein|Martin|M|', 'Berendse|Henk W|HW|', 'van de Berg|Wilma D J|WDJ|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D016229:Amyloid beta-Peptides D001288:Attention D001369:Axons D015415:Biomarkers D003072:Cognition Disorders D003430:Cross-Sectional Studies D056344:Executive Function D005260:Female D006801:Humans D007382:Intermediate Filaments D007802:Language D016014:Linear Models D008297:Male D008568:Memory D008569:Memory Disorders D008875:Middle Aged D015999:Multivariate Analysis D009483:Neuropsychological Tests D010300:Parkinson Disease D010446:Peptide Fragments D010766:Phosphorylation D051844:alpha-Synuclein D016875:tau Proteins
CSF biomarkers cognitive impairment Parkinson′s disease neuropsychological testing