# Rapid frontotemporal gray matter loss in proposed body-first Parkinson’s disease: a longitudinal voxel-based morphometry study

## TL;DR

This study shows that body-first Parkinson’s disease causes faster gray matter loss in specific brain regions compared to brain-first Parkinson’s disease over six years.

## Contribution

The study identifies distinct patterns of gray matter atrophy in body-first Parkinson’s disease using longitudinal MRI data.

## Key findings

- PDRBD+ showed significant GM loss in the medial frontal and left temporal lobes compared to PDRBD−.
- At 48 months, PDRBD+ also showed GM atrophy in the cerebellum.
- GMV changes correlated with cognitive scores and autonomic dysfunction.

## Abstract

The study aimed to compare the progressive gray matter (GM) atrophy between brain-first and body-first Parkinson’s disease (PD) under assumption.

Based on the hypothesis that the timing of rapid eye movement (REM) sleep behavior disorder (RBD) onset relative to motor symptoms may differentiate brain-first from body-first PD subtypes, we stratified PD patients from the Parkinson’s Progression Markers Initiative (PPMI) database into 28 RBD-positive PD patients (PDRBD+), 26 RBD-negative PD patients (PDRBD-), 33 isolated RBD (iRBD) patients, and 35 healthy controls. PDRBD+ and PDRBD− groups underwent 4 visits within 48 months including clinical assessments and structure MRI. We measured GM atrophy cross-sectionally and longitudinally and analyzed their associations with other proposed markers.

At baseline, all groups were comparable and showed no significant difference in GM volume (GMV). The longitudinal GMV analysis (group-by-time interaction) showed that, compared with PDRBD− group, PDRBD+ demonstrated significant GM loss in the medial surface of the frontal lobes and the left temporal lobe. In the comparison at the 48th month, besides the bilateral frontotemporal lobes, the PDRBD+ group showed significant GM atrophy in the bilateral cerebellum. The two groups had no significant differences in the 12th and 24th months. Over time, each PD group showed extensive cortical GM loss and bilateral caudate and putamen atrophy. The altered GMV (interaction effect) was positively associated with the MoCA scores and negatively with SCOPA-AUT. Furthermore, the group-level F-statistic map highlighted spatially distinct differences in the protein metabolism, signal transduction, and autophagy pathways between PDRBD+ and PDRBD− groups.

Body-first PD patients show a relatively rapid GMV loss in specific frontotemporal regions (e.g., left middle temporal gyrus) within 6 years following motor symptoms. Our findings add further evidence to the α-synuclein spreading hypothesis.