Novel Biomarkers of Cognitive Decline in Parkinson’s Disease Revealed

Highlights:

• Cognitive decline associated with Parkinson's disease can be a debilitating condition but it is often identified only after there has been considerable damage to the neurons.
• Interventional strategies post the onset of cognitive decline are aimed at protecting the few healthy neurons that still persist.
• New biomarkers can be used to identify the risk of cognitive decline early, that can help devise early interventional strategies to protect the neurons.

A research team from University of Pennsylvania's Perelman School of Medicine has identified novel biomarkers to predict cognitive impairment in Parkinson's disease. These biomarkers can be used to determine which Parkinson's disease patients will suffer from significant cognitive decline during the initial three years of the disease progression. The study, with potential benefits in improving care for Parkinson's disease patients, was published in the Journal PLoS ONE.

Professor of Psychiatry, Dr. Daniel Weintraub, who is the lead author of the study, said that the findings could be used to improve the understanding of the changes that occur in the brain, that are associated with cognitive decline. The clinical care of Parkinson's disease patients could be improved by detecting the signs of cognitive decline early.

A Landmark Study

The research team led by Dr. Weintraub analyzed 423 newly undiagnosed but untreated Parkinson's disease patients who did not show symptoms of dementia when they were enrolled in the study. This study was sponsored by The Michael J. Fox Foundation for Parkinson's Research and is considered the landmark study which could be used to improve interventional strategies for people with Parkinson's disease.

What were the findings from the study?

The study found that

• 15 to 38 % of the study participants developed cognitive decline three years after they enrolled in the study.

The research team conducted genetic tests, brain scans and analyses of cerebrospinal fluid (CSF) and found that cognitive decline correlated with several biomarkers like

• Lowered brain volume and thickness, indicative of atrophy of the brain
• Genetic mutations - single nucleotide polymorphisms in the COMT and the BDNF genes
• Deficiency in Dopamine
• Lower levels of beta-amyloid protein, a marker of Alzheimer's disease

Clinicians can use the information in the study to identify patients who are at high risk and provide them with interventional strategies which could delay the onset or utilize efforts to enhance their cognitive skills.

This study involved only white males who were newly diagnosed with Parkinson's disease; further studies that include people from other ethnic backgrounds will help validate the effectiveness of these biomarkers in determining cognitive decline across ethnicities. The studies will also help in identifying if the novel biomarkers are risk factors for late onset Parkinson's disease or whether they are indicators of cognitive decline.

Parkinson's Disease

This is one of the most significant neurodegenerative diseases that affect millions of people across the world.

• Nearly 1 million Americans live with Parkinson's disease
• More than 5 million people worldwide live with Parkinson's disease
• 60,000 Americans are diagnosed every year while there are many who go undetected

This common and incapacitating neurodegenerative disease affects many people but is generally detected among people over the age of 60 years. The major symptoms of the disease include

• Akinesia
• Bradykinesia
• Tremor
• Postural instability

The diagnosis of this condition is largely dependent on an assessment of symptoms. It is routinely misdiagnosed with other neurodegenerative diseases in the clinical setting; misdiagnosis occurs

• 50% of the time in primary care
• 10% of the time by movement specialists

The current methods of ascertaining the condition are based on the presence of Lewy bodies and Lewy neurites in the residual neurons or axons during postmortem analysis. The diagnosis of this condition occurs very late, when 50-60% of dopaminergic neurons in the substatia nigra are lost. This limits the effectiveness of the treatment strategies as the number of remaining neurons is very low.

Therefore, there is an urgent need to identify biomarkers associated with the condition so that treatment strategies help the patient before there has been considerable damage to the neurons. The current study identified potential biomarkers which can be used to identify patients who are at high risk for cognitive decline even before the symptoms set in. Nearly 10 to 15% of the Parkinson's disease incidences are believed to be due to genetic factors. An individual is at high risk of developing the condition when the mother, father or the sibling has the condition. Three genes have been previously found to be associated with Parkinson's disease, namely PARK2, LRRK2 and Glucocerebrosidase.

The current study identified polymorphisms in two genes, COMT and BDNF, which are found to be indicators of cognitive decline. Genetic testing could be used to identify high risk patients so that better treatment modalities may be used to delay cognitive decline.

References:

1. A Landmark Study of Parkinson's Disease - (http://www.ppmi-info.org/)

Source-Medindia