Parkinson's disease affects about half a million people in the United States. New research identifies biomarkers that could predict the cognitive impairment typical of this neurodegenerative disease.

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New research has identified four biomarkers that could predict cognitive deficits in patients with Parkinson's disease.

Parkinson's disease (PD) is "the second most common neurodegenerative disease after Alzheimer's disease," according to the Centers for Disease Control and Prevention (CDC).

In the U.S., approximately 50,000 people receive a PD diagnosis every year. Additionally, 500,000 Americans are estimated to be living with PD.

While there is no cure for PD, there are therapies that aim to slow down the advancement of the disease. Usually, however, PD is diagnosed when the symptoms become apparent, by which time the neurons affected have already been lost. This reduces the effectiveness of treatments that aim to delay PD's progression.

As the National Institutes of Health (NIH) explain, having "measurable indicators" of the disease - or biomarkers - could improve the efficacy of potential treatments, enabling clinicians to diagnose PD earlier on, before it has created irreparable damage. An early detection of the condition would also facilitate clinical trials and allow researchers to test novel therapies.

A new study - published in the journal PLOS One - identifies biomarkers which help predict PD-related cognitive impairment. The new research suggests that the biomarkers identified could predict who among those diagnosed with PD will develop cognitive decline in the first 3 years after diagnosis.

The study was led by Dr. Daniel Weintraub, from the University of Pennsylvania, PA, and received funding from the National Institute of Neurological Disorders and Stroke - part of the NIH - and the Michael J. Fox Foundation for Parkinson's Research.

Brain atrophy, dopamine deficits, and genes predict cognitive decline

The researchers examined 423 patients from 33 international centers for movement disorder, who had recently been diagnosed with PD. The patients had no symptoms of cognitive decline at the beginning of the study, in 2010.

The patients were clinically followed for 3 years. In order to assess the predictive potential of certain biomarkers, the researchers conducted a series of tests.

They analyzed 11 single nucleotide polymorphisms (SNPs, or genetic variations) that had been previously associated with cognition in PD. They also analyzed the cerebrospinal fluid - looking at beta-amyloid, tau, and alpha synuclein levels. Finally, they ran a range of brain scans - including magnetic resonance imaging (MRI) and computed tomography (CT).

Dr. Weintraub and colleagues looked at dopamine transporters, which are proteins that control the dynamic of the dopamine neurotransmitter in the brain and whose abnormal levels have been previously associated with PD. They also examined the volume and thickness of the brain.

Overall, throughout the study, 15-38 percent of the patients developed cognitive impairment.

The biomarkers that were found to predict this cognitive decline were: a deficiency in dopamine, a "diffuse" decrease in the brain volume across the frontal, temporal, parietal, and occipital lobes, pathological levels of beta-amyloid plaques - just like those found in Alzheimer's disease - and some genetic variations.

The study found SNPs in the COMT and BDNF genes, which had been previously shown to correlate with cognitive impairment.

The lead investigator reviews the key findings of the study:

"Cognitive impairment in de novo Parkinson's disease increases in frequency 50-200 percent in the first several years of disease depending on the definition used, and is independently predicted by biomarker changes related to nigrostriatal or cortical dopaminergic deficits, global atrophy due to possible widespread effects of neurodegenerative disease, co-morbid Alzheimer's disease amyloid plaque pathology, and a mix of genetic factors."

Dr. Daniel Weintraub

Some of the limitations of the research include the study's sample, which consisted largely of white, highly educated males. Therefore, the findings cannot be generalized to other socioethnic groups. However, should the results be confirmed by follow-up studies, they will help researchers design clinical trials for therapies that may prevent PD-related cognitive decline.

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