Brain Atrophy as a Potential Biomarker of Cognitive Impairment in Parkinson Disease

In addition to motor symptoms, Parkinson disease (PD) can also result in nonmotor symptoms like cognitive impairment and eventual dementia. Researchers have identified brain structure changes associated with worsening cognition in hopes that it can lead to a better understanding of the mechanisms of PD.

Patients with PD are more likely to develop dementia if they have PD with mild cognitive impairment (PD-MCI), but prior research into brain structure changes associated with PD-MCI has been inconsistent. The current study, published in CNS Neuroscience & Therapeutics, aimed to identify structural alterations in the brains of patients who develop PD-MCI as well as to determine the levels of neurotransmitters and proteins associated with cognitive impairment.

Researchers recruited participants who were enrolled in the multisite, international Parkinson’s Progression Marker Initiative. The study included 94 patients with PD who had normal cognition at baseline and 32 healthy controls; over a mean of 28 months follow-up, 24 of the patients with PD developed PD-MCI and were termed “converters,” and the remaining 70 were classified as “nonconverters.”

Investigators assessed participants’ motor symptoms with 2 rating scales, levodopa equivalent daily dose of dopaminergic (LEDD) drugs, cerebrospinal fluid (CSF) specimens, performance on neuropsychological tests, dopamine transporter (DAT) imaging scans via computed tomography, and magnetic resonance imaging scans.

As determined by DAT imaging at baseline, patients with PD had significantly lower striatal binding ratios in their left and right caudate and left and right putamen brain areas compared with the healthy controls (all P <.001), but there were no differences in these ratios between those who converted to PD-MCI and those who did not. Converters had poorer scores for cognitive performance than nonconverters and controls at baseline, but there was no association between LEDD and cognitive test performance in either PD group.

Analysis of gray matter volume (GMV), a measure of brain atrophy, revealed that converters had greater atrophy in the right temporal pole at baseline than the nonconverters. At follow-up, converters had significantly reduced GMV relative to nonconverters in the right temporal poles of the right middle temporal lobe, and they also had significant atrophy in the right inferior temporal lobe compared with healthy controls.

Over follow-up, converters developed increased gray matter atrophy in both frontal lobes compared with nonconverters, whereas there was no significant difference in GMV alteration between the nonconverters and healthy controls. There was no correlation found between altered GMV and CSF proteins in any group.

When assessing the relationships between brain volume changes and cognitive scores, researchers determined that, in converters, mean volume of frontal lobes at follow-up was positively correlated with scores on the Letter-Number Sequencing test (P = .044) and mean volume of the right superior temporal lobe was positively correlated with scores of semantic fluency (P = .016).

Based on similarity to findings of previous research, the study authors wrote that “this highly consistent result further supports the opinion that lower temporal volume might be an important marker of the conversion to PD&#8208;MCI in the future.” They also noted that their study was the first to find a longitudinal difference between converters and nonconverters in progressive frontal atrophy of the superior frontal lobes.

Imaging studies may thus be a useful tool for predicting cognitive impairment in patients with PD, the authors suggested. Their findings also point toward associations among brain atrophy, cognition, and DAT imaging.

“In conclusion, early atrophy in right temporal lobe and progressive atrophy in frontal lobes might be biomarkers for developing multidomain impairment of cognition and converting to PD&#8208;MCI,” they wrote. “Furthermore, cognition&#8208;related temporal atrophy might be associated with dopaminergic deficit reflected by DAT scan but independent of CSF proteins in patients with PD who convert to PD&#8208;MCI.”

Reference

Zhou C, Guan XJ, Guo T, et al. Progressive brain atrophy in Parkinson’s disease patients who convert to mild cognitive impairment [published online July 6, 2019]. CNS Neurosci Ther. doi: 10.1111/cns.13188.