Cerebral microstructural alteration patterns in motor subtypes of Parkinson's disease: a neurite orientation...

Tremor-dominant (TD) and postural instability and gait difficulty (PIGD) are motor subtypes of Parkinson's disease (PD) characterized by distinct clinical and disease progression. For these subtypes, the microstructural alterations in white matter (WM) and gray matter (GM), such as axonal density or dispersion, remain unclear. We aimed to ascertain distinct microstructural alterations in WM and GM between TD and PIGD, explicating neuroanatomical differences underlying these diverse clinical presentations.

This study analyzed WM and GM microstructures using neurite orientation dispersion and density imaging (NODDI). Totals of 74 patients with PD and 47 age- and sex-matched healthy controls (HCs) were included. Tract-based spatial statistics (TBSS) and GM-based spatial statistics (GBSS) were applied to evaluate NODDI-derived metrics across groups.

A total of 24 TD patients (40.0%) and 36 PIGD patients (60.0%) were included for TBSS. In WM, PIGD showed a higher orientation dispersion index (ODI) in corona radiata compared to TD, and a lower neurite density index (NDI) in multiple WM tracts than HCs [P_{family-wise error (FWE)}<0.05]. Totals of 22 TD patients (39.3%) and 34 PIGD patients (60.7%) were included for GBSS. In GM, both subtypes exhibited widespread reductions in NDI, particularly in temporal lobes, with PIGD showing a greater reduction range (P_FWE<0.05). The microstructure of WM (PIGD: r=-0.66, P_FWE<0.001; TD: r=0.71, P_FWE<0.001) and putamen (TD: r=0.71, P_FWE=0.001) were significantly correlated with cognition in subtypes.

PIGD exhibited more extensive cerebral microstructural alterations than TD, and the microstructures showed significant cognitive correlations. NODDI-derived metrics may serve as potential biomarkers for cognitive and motor symptom assessment in PD.