Penn Medicine researchers identify biomarkers that may predict cognitive impairment in new Parkinsonâs disease patients
Penn Medicine News May 25, 2017
New biomarkers identified by a research team in the Perelman School of Medicine at the University of Pennsylvania could help predict which ParkinsonÂs disease patients will suffer significant cognitive deficits within the first three years of their diagnosis. The results of the analysis from the international ParkinsonÂs Progression Markers Initiative (PPMI) were published in the journal PLoS ONE.
ÂThe results of this study improve our understanding of the changes in brain function that occur with initial cognitive changes in early ParkinsonÂs disease, said Daniel Weintraub, MD, a professor of Psychiatry and lead author. ÂThis could eventually lead to improved clinical care and development of therapies to treat this symptom.Â
Dr. Weintraub led the team that analyzed data and samples from 423 newly diagnosed and untreated ParkinsonÂs disease patients who showed no signs of dementia at the time of their enrollment in PPMI, a landmark observational study launched in 2010 and sponsored by The Michael J. Fox Foundation for ParkinsonÂs Research.
Three years after enrollment, between 15 and 38 percent of these participants had developed cognitive impairment. The authors assessed brain scans, genetic tests and analyses of cerebrospinal fluid (CSF) and found cognitive decline correlated with several biomarkers: changes in the dopamine system, global brain atrophy, particular genetic mutations, and markers of AlzheimerÂs disease.
This is the first investigation to find each of these biomarkers, a mix of baseline and longitudinal biomarkers, contributes independently to cognitive decline in early ParkinsonÂs disease. These results may improve the ability of clinicians to predict future cognitive performance in ParkinsonÂs disease patients – an important part of patient education and clinical management – and may guide efforts to develop new cognition–enhancing treatments for ParkinsonÂs disease.
Other Penn co–investigators include Leslie Shaw, PhD, a professor of Pathology and Laboratory Medicine; John Trojanowski, MD, PhD, professor of Geriatric Medicine and Gerontology; and Lama Chahine, MD, an assistant professor of Neurology.
In this study, researchers found an association between cognitive decline and (i) dopamine deficiency and (ii) decreased brain volume or thickness observed in brain scans; (iii) lower levels in CSF of beta–amyloid protein, a marker of AlzheimerÂs disease, and (iv) single nucleotide polymorphisms in the genes COMT and BDNF, which previously had been associated with cognitive impairment.
This cohort of PPMI participants are mostly male, white and highly educated, limiting the application of these findings to other groups. Nonetheless, future validation of these biomarkers could help with clinical trial design for early therapies that may improve cognitive outcomes. Longer follow–up of this cohort will also reveal whether the identified risks are important in later–onset or more advanced cognitive dysfunction in ParkinsonÂs disease.
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ÂThe results of this study improve our understanding of the changes in brain function that occur with initial cognitive changes in early ParkinsonÂs disease, said Daniel Weintraub, MD, a professor of Psychiatry and lead author. ÂThis could eventually lead to improved clinical care and development of therapies to treat this symptom.Â
Dr. Weintraub led the team that analyzed data and samples from 423 newly diagnosed and untreated ParkinsonÂs disease patients who showed no signs of dementia at the time of their enrollment in PPMI, a landmark observational study launched in 2010 and sponsored by The Michael J. Fox Foundation for ParkinsonÂs Research.
Three years after enrollment, between 15 and 38 percent of these participants had developed cognitive impairment. The authors assessed brain scans, genetic tests and analyses of cerebrospinal fluid (CSF) and found cognitive decline correlated with several biomarkers: changes in the dopamine system, global brain atrophy, particular genetic mutations, and markers of AlzheimerÂs disease.
This is the first investigation to find each of these biomarkers, a mix of baseline and longitudinal biomarkers, contributes independently to cognitive decline in early ParkinsonÂs disease. These results may improve the ability of clinicians to predict future cognitive performance in ParkinsonÂs disease patients – an important part of patient education and clinical management – and may guide efforts to develop new cognition–enhancing treatments for ParkinsonÂs disease.
Other Penn co–investigators include Leslie Shaw, PhD, a professor of Pathology and Laboratory Medicine; John Trojanowski, MD, PhD, professor of Geriatric Medicine and Gerontology; and Lama Chahine, MD, an assistant professor of Neurology.
In this study, researchers found an association between cognitive decline and (i) dopamine deficiency and (ii) decreased brain volume or thickness observed in brain scans; (iii) lower levels in CSF of beta–amyloid protein, a marker of AlzheimerÂs disease, and (iv) single nucleotide polymorphisms in the genes COMT and BDNF, which previously had been associated with cognitive impairment.
This cohort of PPMI participants are mostly male, white and highly educated, limiting the application of these findings to other groups. Nonetheless, future validation of these biomarkers could help with clinical trial design for early therapies that may improve cognitive outcomes. Longer follow–up of this cohort will also reveal whether the identified risks are important in later–onset or more advanced cognitive dysfunction in ParkinsonÂs disease.
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