Predicting Cognitive Deficits

Parkinson’s disease is commonly thought of as a movement disorder, but after years of living with the disease, approximately 25 percent of patients also experience deficits in cognition that impairs function. A newly developed research tool may help predict a patient’s risk for developing dementia and could enable clinical trials aimed at finding treatments to prevent the cognitive effects of the disease.

The research was published in Lancet Neurology www.thelancet.com and was partially funded by the NIH National Institute of Neurological Disorders and Stroke (NINDS) www.ninds.nih.gov.

The team of researchers was led by Clemens Scherzer, M.D., Head of the Neurogenomics Lab and the Parkinson Personalized Medicine Program at Harvard Medical School and a Member of the Center for Neurologic Diseases at Brigham and Women’s Hospital in Boston.

Currently, Parkinson’s medications are only effective in improving motor deficits caused by the disease. One barrier to developing treatments for the cognitive effects of Parkinson’s is the considerable variability among patients. As a result, researchers must enroll several hundred patients when designing clinical trials to test treatments.

The team combined data from 3,200 people with Parkinson’s disease, which represented more than 25,000 individual clinical assessments and the researchers then evaluated seven known clinical and genetic risk factors associated with developing dementia.

The next step for the research team was to build a computer-based risk calculator that could possibly predict the chance that an individual with Parkinson’s will develop cognitive deficits. “By calculating risks, it would be possible to identify and select only patients at high-risk for developing dementia. This tool could help in the design of smarter trials that require a manageable number of participating patients,” reports Dr. Scherzer.

One problem in using the risk calculator in clinics is the lack of available treatments for Parkinson’s-related cognitive deficits. Doctors face ethical issues concerning whether patients should be informed of their risk when there is little available to help them.

It is hoped that by improving clinical trial design, the risk calculator can aid in the discovery of new treatments and determine which patients would benefit most from the new treatments. “Prediction is the first step, said Dr. Scherzer. “Prevention is the ultimate goal, in hopes of preventing a dismal prognosis from ever happening.”

Moving forward, Dr. Scherzer and colleagues from the International Genetics of Parkinson’s Disease Progression (IGPP) Consortium plan to further improve the cognitive risk score calculator.

The team is now scanning the genome of patients to hunt for new progression genes. Ultimately, the hope is that the tool can be used in clinics but also help with clinical trial design. However, considerable research remains to be done before that will be possible.

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