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Immunohistochemistry for alpha-synuclein
showing positive staining (brown) of an intraneural Lewy-body in the Substantia
nigra in Parkinson's disease. Credit: Wikipedia
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February 17, 2016
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.
Explore further: Widespread brain
atrophy detected in Parkinson's disease with newly developed structural pattern
More information:
Ragnhild E. Skogseth et al. Associations between Cerebrospinal Fluid Biomarkers
and Cognition in Early Untreated Parkinson's Disease, Journal of Parkinson's
Disease (2015). DOI:
10.3233/JPD-150682
http://medicalxpress.com/news/2016-02-biomarker-early-cognitive-decline-parkinson.html?
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