New biomarkers may help forecast cognitive decline in Parkinson's disease patients

After an analysis of the international Parkinson’s Progression Markers Initiative (PPMI), a landmark observational study sponsored by The Michael J. Fox Foundation for Parkinson’s Research, researchers from Penn Medicine have found new biomarkers that may help predict which patients with Parkinson’s disease will experience significant cognitive deficits within the first 3 years of their diagnosis. They published their results in the journal PLoS One.

In the United States, an estimated 1 million people live with Parkinson’s disease, and annually, an additional 60,000 are diagnosed each year. Still, estimates hold that thousands of cases go undetected.

“The results of this study improve our understanding of the changes in brain function that occur with initial cognitive changes in early Parkinson’s disease,” said lead author Daniel Weintraub, MD, professor of psychiatry, Perelman School of Medicine, Philadelphia, PA. “This could eventually lead to improved clinical care and development of therapies to treat this symptom.”

For their analysis, Dr. Weintraub and fellow researchers included data and samples from 425 patients who were newly diagnosed and untreated for Parkinson’s disease. At the time patients enrolled in the PPMI, none showed signs of dementia. Patients were primarily male, white, and highly educated.

Three years after enrollment into PPMI, between 15% and 38% of patients had developed cognitive impairment. Upon assessment of patient brain scans, genetic tests, and cerebrospinal fluid (CSF), Dr. Weintraub and colleagues found that cognitive decline was correlated with the following biomarkers: changes in the dopamine system, global brain atrophy, specific genetic mutations, and markers of Alzheimer’s disease.

A combination of baseline and longitudinal biomarkers independently contributes to cognitive decline in early Parkinson’s disease, according to an analysis conducted by researchers at the Perelman School of Medicine, Philadelphia, PA.

Specifically, they found associations between cognitive decline and dopamine deficiency, decreased brain volume, lower CSF levels of ß-amyloid protein (a marker of Alzheimer’s disease), and single nucleotide polymorphisms in the COMT val/val and BDNF val/val genotypes, which were found previously to have an association with cognitive impairment.

The Parkinson’s Progression Markers Initiative is a public-private partnership funded by The Michael J. Fox Foundation and 20 industry partners. This analysis was also funded in part by the National Institute of Neurological Disorders and Stroke, part of the National Institutes for Health (P50 NS053488).