Brain imaging distinguishes Parkinson’s subtypes

Patients with nontremor-dominant Parkinson's disease (PD) show changes in brain activity that set them apart from tremor-dominant patients and from healthy controls, a study shows.

Researchers found cortical and subcortical differences between patients with the nontremor- and tremor-dominant phenotype that were not accounted for by differences in white and gray matter volume.

"These findings suggest that objective measures of brain function may be useful in future genotype-phenotype analyses and in targeted therapeutic trials focused on PD subtypes," say David Vaillancourt (University of Florida, Gainesville, USA) and co-workers.

In general, patients with the nontremor-dominant subtype had multiple differences in brain activation relative to those with tremor-dominant PD and to controls, whereas those with the tremor-dominant subtype had just one marked difference compared with controls.

The 20 drug-naive PD patients in the study underwent functional magnetic resonance imaging while performing a grip task, which the team says "requires robust activation of frontal cortical regions and parietal cortical regions."

The only cortical area that showed significantly different brain activity between PD subtypes in both voxelwise and region-of-interest analysis was the ipsilateral dorsolateral prefrontal cortex (DLPFC). This showed reduced activation in the 10 patients with nontremor-dominant PD compared with 10 who had the tremor-dominant subtype.

This "suggests that this prefrontal area is robustly sensitive to differences in patients clustered into tremor- and nontremor-dominant groups," the researchers write in the Archives of Neurology. They add: "The DLPFC has been suggested to play an important role in working memory and executive function."

Patients with nontremor-dominant PD also had reduced ipsilateral DLPFC activation relative to 20 healthy controls, whereas those with tremor-dominant PD had increased contralateral DLPFC activation.

Relative to patients with tremor-dominant PD, those with the nontremor-dominant subtype also had reduced activation of several subcortical areas - namely, the contralateral globus pallidus interna and globus pallidus externa (nuclei of the basal ganglia), the ipsilateral thalamus, the inferior parietal lobule, and the precuneus areas. But only the contralateral globus pallidus interna and globus pallidus externa had reduced activation in nontremor-dominant patients versus controls.

Vaillancourt et al comment that the basal ganglia have "established connections with the DLPFC," and so the reduced activation seen in the DLPFC could be directly related to changes in the basal ganglia nuclei.

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