CSF Biomarkers Reflecting Protein Pathology and Axonal Degeneration Are Associated with Memory, Attentional, and Executive Functioning in Early-Stage Parkinson's Disease.

Linda P Oosterveld,Omar M El-Agnaf,Henry C Weinstein,Inge M W Verberk,Henk W Berendse,Nour K Majbour,Tessa I Kuiper,Charlotte E Teunissen,Wilma D J Van De Berg,Jos W R Twisk,Karin D Van Dijk,Martin Klein

doi:10.3390/ijms21228519

Abstract

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.

Highlights

Cognitive impairment is a common non-motor symptom in early-stage Parkinson s disease (PD), and can have a major negative impact on the patient s quality of life [1]
NfL, neurofilament light chain. p-tau, phosphorylated tau. sβ, standardized β-coeffi3.cDieinsctu. ssion. In this cross-sectional study, we aimed to explore whether cerebrospinal fluid (CSF) biomarkers reflecting protein pathology and axonal degeneration are associated with cognitive performance in early-stage PD
In this cross-sectional study, we aimed to explore whether CSF biomarkers reflecting protein pathology and axonal degeneration are associated with cognitive performance in early-stage PD patients

Summary

Introduction

Cognitive impairment is a common non-motor symptom in early-stage Parkinson s disease (PD), and can have a major negative impact on the patient s quality of life [1]. At the time of diagnosis, about 20–35% of PD patients meet criteria for mild cognitive impairment (PD-MCI) [2], which is associated with an increased risk of developing comorbid dementia [3]. The majority of previous cross-sectional studies analyzed CSF biomarkers in PD populations with a long disease duration, while it is important to study these relations in the earliest stages of disease to identify patients who are at an increased risk for developing cognitive impairment. From the few studies that investigated cognitive impairment in early-stage PD patients, the most consistent finding was a positive association between CSF Aβ42 levels and memory functioning [7,11,12]. Whether CSF p-α-syn and CSF NfL are associated with cognitive functioning in early PD remains to be determined

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