Imaging Biomarkers May Track Parkinson's Progression

Nancy A. Melville

August 30, 2016

Parkinson's disease and other atypical parkinsonian syndromes demonstrate unique patterns of progression in cortical and subcortical regions of the brain that correlate with decline in function, providing potential biomarkers for neurodegeneration, a new longitudinal study of patients over the course of a year suggests.

"We have provided a marker of functional brain activity based on noninvasive magnetic resonance imaging [MRI] technology to track progression in Parkinson's disease and parkinsonism," senior author David E. Vaillancourt, PhD, a professor in the University of Florida's Department of Applied Physiology and Kinesiology, Gainesville, told Medscape Medical News.

"This may allow evaluation of disease-modifying therapeutics in the future."  

The study was published in the August 16 issue of Neurology.

Dr Vaillancourt and colleagues performed functional MRI (fMRI) on 112 patients while they were performing grip strength tasks, including 46 with Parkinson's disease (32 of whom had atypical parkinsonism: 13 with multiple system atrophy [MSA] and 19 with progressive supranuclear palsy [PSP]) and 34 healthy controls.

A comparison of fMRI at baseline and after 1 year showed that patients with Parkinson's disease had significantly greater declines in the putamen and primary motor cortex regions of the brain compared with healthy controls.

Whereas patients with Parkinson's disease have been shown to have reduced activity in the primary motor cortex, the study is the first to indicate a worsening of the deficit over time.

"We extend the existing literature on [Parkinson's disease] by showing that functional activity of the primary motor cortex, which has been consistently shown to be reduced in these patients, continues to deteriorate with disease progression," the authors write.

The fMRIs for patients with MSA, meanwhile, showed different neurodegenerative patterns, with changes that were exclusively extrastriatal, including a reduction in functional activity in the primary motor cortex, supplementary motor area, and superior cerebellum.

Among patients with PSP, reductions in activity were observed in all regions of interest after 1 year compared with baseline.

No similar changes were observed in the control group.

The patients, who were referred by the University of Florida Center for Movement Disorders and Neurorestoration, had an average diagnosis period that was stable for more than 3 years, and while most were taking antiparkinsonian medication, testing was performed 12 to 14 hours after overnight withdrawal of the medication.

The findings offer important clues as to how parkinsonian disorders progress over time, the authors say.

"Although the use of MRI in parkinsonian disorders has increased in recent years, there are no [previous] longitudinal studies that monitor and compare the progression of cortical and subcortical function between these disorders," the authors write.

They add that "Collectively, these findings point to disease-specific noninvasive progression markers of sensorimotor brain regions in parkinsonian disorders."

Dr Vaillancourt noted that such markers could have highly important clinical implications.

"If reliable and valid markers are identified, this can open the door to testing disease-modifying therapies in much the same way that this has occurred in multiple sclerosis," he said.

Future research should, importantly, include clinical subtypes of Parkinson's disease or atypical parkinsonian syndromes, he added.

"Few studies have examined parkinsonism," Dr Vaillancourt said. "These diseases have symptoms that overlap with Parkinson's disease, and need further attention."

Debra Babcock, MD, PhD, program director at the National Institutes of Healths National Institute of Neurological Disorders and Stroke, agreed that the study provides much-needed insights into ongoing efforts to understand Parkinson's disease.

"For decades, the field has been searching for an effective biomarker for Parkinson's disease," she said in a press statement.

"This study is an example of how brain imaging biomarkers can be used to monitor the progression of Parkinson's disease and other neurological disorders."

The study received support from the National Institutes of Health. Dr Vaillancourt reports grants from the National Institutes of Health, Bachmann-Strauss, and Tyler's Hope Foundation during the conduct of the study. The authors' other disclosures are available in the online version of the study.

Neurology. 2016; 87:709-717. Abstract

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