Neuroimaging evidence of microstructural alteration in Parkinson’s disease with subjective cognitive decline

Abstract Subjective cognitive decline (SCD) may represent a special cognitive stage distinct from mild cognitive impairment (MCI) in Parkinson’s disease (PD), but its microstructural correlates are underexplored. We aimed to investigate microstructural alterations in PD-SCD compared to PD with normal cognition (PD-NC) and PD-MCI, and to explore their association with cognitive status. 68 PD patients (PD-NC: n = 23; PD-SCD: n = 20; PD-MCI: n = 25) and 27 healthy controls (HC) underwent multimodal MRI. Analyses included tract-based spatial statistics (TBSS), calculation of the peak width of skeletonized mean diffusivity (PSMD), and hippocampal subfield segmentation. PSMD showed significant differences across subgroups and negatively correlated with MoCA scores, suggesting its utility as a metric that differentiated cognitive stage. TBSS revealed reduced fractional anisotropy (FA) in multiple tracts in PD-MCI, while PD-SCD exhibited reduced FA only in FMajor relative to HC. Hippocampal subfield segmentation revealed atrophy in subregions such as CA1 and HATA in PD-SCD and PD-MCI compared to PD-NC. This study provides evidence that microstructural alterations are already detectable at the PD-SCD stage. PSMD emerges as a sensitive cross-sectional biomarker of PD cognitive staging. These findings highlight the potential role of white‑matter changes in PD‑related cognitive complaints.