A worldwide study of white matter microstructural alterations in people living with Parkinson's disease

Area of Science:

• Neuroimaging
• Neuroscience
• Biomedical Engineering

Background:

• Parkinson's disease (PD) progression is linked to neural pathway microstructural changes, impacting motor and cognitive functions.
• Previous studies on white matter alterations in PD yielded conflicting results due to methodological heterogeneity and small sample sizes.

Purpose of the Study:

• To investigate stage-specific white matter microstructural differences in Parkinson's disease using a large, multi-cohort diffusion MRI dataset.
• To characterize the evolving profile of white matter alterations across different Hoehn and Yahr (HY) disease stages.

Main Methods:

• Analysis of diffusion-weighted MRI data from 1654 PD patients and 885 controls across 17 international cohorts.
• Utilized the ENIGMA-DTI protocol to assess white matter microstructure, focusing on fractional anisotropy (FA) and mean diffusivity (MD).
• Compared skeletonized FA and MD maps across PD HY disease stages (1-5) and controls.

Main Results:

• A progressive and widespread pattern of microstructural alterations was observed with increasing PD severity.
• Later PD stages (HY 4/5) showed significantly lower FA and higher MD across most regions, with large effect sizes (e.g., Cohen's d = -1.01 for FA in the fornix).
• Early PD (HY stage 1) presented a distinct signature of higher FA and lower MD, contrasting with other neurodegenerative diseases and potentially indicating compensatory changes.

Conclusions:

• White matter microstructural alterations intensify with Parkinson's disease progression.
• Early-stage PD is characterized by paradoxical increases in FA and decreases in MD, likely reflecting early compensatory neural mechanisms.
• These findings highlight the dynamic nature of white matter changes in PD and their association with clinical symptoms.