Researchers identify biomarker for early cognitive decline in Parkinson's disease patients

February 17, 2016
Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

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 ," 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 , 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 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 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: Use of anticholinergic drugs does not increase risk for dementia in Parkinson's disease patients

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

Related Stories

Use of anticholinergic drugs does not increase risk for dementia in Parkinson's disease patients

January 4, 2016
Recent evidence has shown a greater risk of dementia, in particular Alzheimer's disease (AD), in individuals using anticholinergic medications regularly. These drugs are widely used by older adults to treat bladder dysfunction, ...

Cell-free circulating mtDNA identifies Parkinson's disease

December 10, 2015
(HealthDay)—Cell-free circulating mitochondrial DNA (ccf-mtDNA) from cerebrospinal fluid (CSF) is reduced in patients with Parkinson's disease (PD), according to research published in the December issue of the Annals of ...

Mild cognitive impairment at Parkinson's disease diagnosis linked with higher risk for early dementia

March 25, 2013
Mild cognitive impairment at the time of Parkinson disease (PD) diagnosis appears to be associated with an increased risk for early dementia in a Norwegian study, according to a report published Online First by JAMA Neurology.

Widespread brain atrophy detected in Parkinson's disease with newly developed structural pattern

December 12, 2011
Atrophy in the hippocampus, the region of the brain known for memory formation and storage, is evident in Parkinson's disease (PD) patients with cognitive impairment, including early decline known as mild cognitive impairment ...

Higher levels of CSF alpha-synuclein predict faster cognitive loss in Parkinson disease

March 11, 2014
The course of Parkinson disease (PD) can vary from gradual deterioration to precipitous decline in motor or cognitive function. Therefore identifying predictors of progression can benefit understanding of PD disease progression ...

Five CSF markers differentiate dementia, parkinsonism

August 28, 2012
(HealthDay)—Levels of five different cerebrospinal fluid (CSF) biomarkers are able to improve differentiation between common dementia and parkinsonian disorders, according to a study published online Aug. 27 in the Archives ...

Recommended for you

Parkinson's is partly an autoimmune disease, study finds

June 21, 2017
Researchers have found the first direct evidence that autoimmunity—in which the immune system attacks the body's own tissues—plays a role in Parkinson's disease, the neurodegenerative movement disorder. The findings raise ...

Predicting cognitive deficits in people with Parkinson's disease

June 20, 2017
Parkinson's disease (PD) is commonly thought of as a movement disorder, but after years of living with PD approximately twenty five percent of patients also experience deficits in cognition that impair function. A newly developed ...

Pre-clinical study suggests Parkinson's could start in gut endocrine cells

June 15, 2017
Recent research on Parkinson's disease has focused on the gut-brain connection, examining patients' gut bacteria, and even how severing the vagus nerve connecting the stomach and brain might protect some people from the debilitating ...

Hi-res view of protein complex shows how it breaks up protein tangles

June 15, 2017
Misfolded proteins are the culprits behind amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, and other neurodegenerative brain disorders. These distorted proteins are unable to perform their normal ...

CRISPR tech leads to new screening tool for Parkinson's disease

June 5, 2017
A team of researchers at the University of Central Florida is using breakthrough gene-editing technology to develop a new screening tool for Parkinson's disease, a debilitating degenerative disorder of the nervous system. ...

Infection with seasonal flu may increase risk of developing Parkinson's disease

May 30, 2017
Most cases of Parkinson's have no known cause, and researchers continue to debate and study possible factors that may contribute to the disease. Research reported in the journal npj Parkinson's Disease suggests that a certain ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.