Daniel Weintraub, MD, professor of Psychiatry in the Perelman School of Medicine at the University of Pennsylvania. Credit: Penn Medicine
New biomarkers
identified by a research team in the Perelman School of Medicine at the
University of Pennsylvania could help predict which Parkinson's disease
patients will suffer significant cognitive deficits within the first three
years of their diagnosis. The results of the analysis from the international
Parkinson's Progression Markers Initiative (PPMI) are published this week in
the open-access journal PLoS ONE.
"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
Daniel Weintraub, MD, a professor of Psychiatry and lead author. "This
could eventually lead to improved clinical care and development of therapies to
treat this symptom."
Dr. Weintraub led
the team that analyzed data and samples from 423 newly diagnosed and untreated
Parkinson's 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 Parkinson's 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
Alzheimer's 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 Parkinson's disease. These results may improve the ability of clinicians
to predict future cognitive performance in Parkinson's disease patients—an
important part of patient education and clinical management—and may guide
efforts to develop new cognition-enhancing treatments for Parkinson's 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
Alzheimer's 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 Parkinson's disease.
As many as one
million Americans and more than five million people worldwide are living with
Parkinson's disease. An additional 60,000 Americans are diagnosed with
Parkinson's disease each year, and this number does not reflect the thousands
of cases that go undetected.
More information: Caspell-Garcia C,
Simuni T, Tosun-Turgut D, Wu I-W, Zhang Y, Nalls M, et al. (2017) Multiple
modality biomarker prediction of cognitive impairment in prospectively followed
de novo Parkinson disease. PLoS ONE 12(5): e0175674. doi.org/10.1371/journal.pone.0175674
https://medicalxpress.com/news/2017-05-biomarkers-cognitive-impairment.html
No comments:
Post a Comment