White matter hyperintensity tissue property spatial variations as a function of cognitive status in Parkinson’s disease

BACKGROUND AND PURPOSE: The pathological relationship between white matter hyperintensities (WMH) and cognitive impairment in Parkinson's disease (PD) remains unclear due to their variable locations, heterogeneity, and limited assessment of underlying tissue properties. This study integrates T2-FLAIR and quantitative MRI (qMRI) to investigate burden, spatial distribution, and extent of tissue alterations in WMH, aiming to elucidate their role in cognitive decline among PD patients. METHODS: A total of 122 age- and sex-matched PD patients and 65 healthy controls (HC) were recruited, with PD patients grouped by Montreal Cognitive Assessment (MoCA) score including normal, mild cognitive impairment (MCI) or PD with dementia (PDD). WMH burden was compared across groups and cognitive status. Water content, T1, and T2* measures were derived from qMRI data and tissue property heatmaps and periventricular distance profiles were constructed for all groups to visualize location-dependent tissue alterations of WMH relative to the lateral ventricles. In addition, voxel-wise analysis was performed to examine the correlation between WMH lesion tissue properties and MoCA scores. RESULTS: WMH volume was significantly higher in PDD compared to other groups (p < 0.05) and negatively correlated with MoCA scores (r = -0.352, p < 0.001). WMH appeared predominantly around the lateral ventricles, with anterior horn involvement common to all groups and posterior horn involvement specific to PDD. qMRI measures were significantly elevated in WMH compared to normal appearing white matter (NAWM) (p < 0.001), with heatmaps showing a negative gradient of tissue property changes from the lateral ventricles to the NAWM. Voxel-wise analysis revealed a significant negative correlation between the qMRI tissue properties of periventricular WMH and MoCA scores, with the strongest association observed in the periventricular WM situated just beyond the boundary of the lateral ventricles. CONCLUSION: Over and above volume differences, the spatial distribution and tissue property variations of WMH were closely linked to cognitive impairment in PD patients, with distinct patterns across different cognitive stages.