Many patients with Parkinson’s Disease (PD) develop mild cognitive impairment (MCI) or dementia. Identifying biomarkers for cognitive impairment could be instrumental in facilitating both early diagnosis of MCI and developing new cognitive-enhancing treatments. New research published in the Journal of Parkinson’s Disease indicates that lower concentrations of α-synuclein in cerebrospinal fluid (CSF) is associated with reduced performance on several cognitive tests.
“This is the largest study exploring the association between CSF biomarkers and cognition in PD, and one of few to explore if α-synuclein is associated with cognitive impairment,” explained lead investigator Ragnhild E. Skogseth, MD, of Haraldsplass Deaconess Hospital and the Department of Clinical Medicine, University of Bergen (Norway).
CSF markers beta-amyloid42 (abeta42), total tau protein (t-tau), phosphorylated tau protein (p-tau), and α-synuclein reflect pathophysiological changes relevant to cognition in PD. If changes in these biomarkers can predict cognitive decline, patients could be informed to seek possible treatments.
Part of the Parkinson’s Progression Markers Initiative (PPMI), an international project focusing on development of biomarkers of progression in PD, this study was comprised of 414 patients with untreated PD without dementia and 196 health control (HC) subjects from 24 clinical sites worldwide. The patients were evaluated for multiple cognitive skills, including visuospatial functions, verbal memory, executive function, and attention. Patients were defined as having MCI (PD-MCI) if they showed impairment on two or more tests, while patients not fulfilling criteria for MCI were classified as having normal cognition (PD-NC). The Unified Parkinson’s Disease Rating Score (UPDRS) was used to evaluate the progression of the disease in the PD patients.
The investigation determined that lower α-synuclein was associated with reduced performance in cognition testing in the whole PD-group. Abeta42 was significantly decreased in PD with mild cognitive impairment compared with controls, while values in PD without MCI were identical to the HC group controls.
After analyzing demographics and the results of CSF analysis, there were no significant differences in gender, age, or education between PD and HC patients. Among the PD patients, 140 PD-MCI subjects were significantly older, had less formal education, and had higher UPDRS scores than the 274 PD-NC subjects.
“The association between reduced CSF α-synuclein concentrations and cognition suggests that α-synuclein pathology contributes to early cognitive impairment in PD, in particular to executive-attentional dysfunction. Longitudinal analyses are needed to determine if this and other CSF biomarkers in early Parkinson’s disease are associated with the risk of future cognitive decline and dementia,” noted Dr. Skogseth.
“This is a very important study that not only gives insight into the mechanisms that might underlie cognitive decline in Parkinson’s disease, but it might also represent the first steps in the development of a much needed biomarker that can predict which patients will develop dementia,” commented Patrik Brundin, MD, PhD, Editor-in-Chief of the Journal of Parkinson’s Disease and Director of the Center for Neurodegenerative Science at Van Andel Research Institute in Grand Rapids, MI.
Source: Daphne Watrin – IOS Press
Image Credit: The image is credited to Marvin 101 and is licensed CC BY SA 3.0.
Original Research: Abstract for “Associations between Cerebrospinal Fluid Biomarkers and Cognition in Early Untreated Parkinson’s Disease” by Skogseth, Ragnhild E.; Bronnick, Kolbjorn; Pereira, Joana B.; Mollenhauer, Brit; Weintraub, Daniel; Fladby, Tormod; and Aarsland, Dag in Journal of Parkinson’s Disease. Published online November 23 2015 doi:10.3233/JPD-150682
Abstract
Associations between Cerebrospinal Fluid Biomarkers and Cognition in Early Untreated Parkinson’s Disease
Background: Mild cognitive impairment and dementia are common, clinically important features of Parkinson’s disease (PD). The underlying disease pathology is heterogeneous and not yet well characterized. Biomarkers for cognitive impairment in PD could aid in diagnostic and prognostic evaluation and in the development of new cognitive enhancing treatments.
Objective: To examine the relationship between CSF markers and cognition in a large, multicenter, cohort study of early, untreated PD, and compare marker concentrations between PD patients with and without MCI and healthy, age-matched controls.
Methods: 414 early, untreated PD (34% with mild cognitive impairment) and 189 healthy, cognitively intact controls with baseline neuropsychological testing and CSF abeta42, t-tau, p-tau181 and α-synuclein results were included. Multiple linear regression models were constructed with a composite cognition factor, or memory-, or visuospatial- or executive-attention domains as dependent variables, and CSF markers, demographic characteristics and MDS-UPDRS III score as predictors.
Results: Lower α-synuclein was associated with reduced performance on the executive-attention domain and the composite cognition factor in the whole PD-group. Abeta42 was significantly decreased in PD with mild cognitive impairment compared with controls after adjusting for covariates, while values in PD without MCI were identical to healthy controls.
Conclusions: The association between reduced CSF α-synuclein concentrations and cognition suggests that α-synuclein pathology contributes to early cognitive impairment in PD, in particular to executive-attentional dysfunction. Longitudinal analyses are needed to determine if this and other CSF biomarkers in early Parkinson’s disease are associated with the risk of future cognitive decline and dementia.
“Associations between Cerebrospinal Fluid Biomarkers and Cognition in Early Untreated Parkinson’s Disease” by Skogseth, Ragnhild E.; Bronnick, Kolbjorn; Pereira, Joana B.; Mollenhauer, Brit; Weintraub, Daniel; Fladby, Tormod; and Aarsland, Dag in Journal of Parkinson’s Disease. Published online November 23 2015 doi:10.3233/JPD-150682
