Diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Parkinson’s disease patients with subjective cognitive decline

Abstract

This study aimed to examine diffusion alterations indexed by the diffusion tensor image analysis along the perivascular space (DTI-ALPS) in patients with Parkinson’s disease presenting with subjective cognitive decline (PD-SCD), and to investigate their associations with impairments across specific cognitive domains. This is a cross-sectional study. A total of 607 eligible participants were enrolled and categorized into three groups: healthy controls (HC), Parkinson’s disease with normal cognition (PD-NC), and PD-SCD. The DTI-ALPS index was calculated as a diffusion-based metric reflecting water diffusivity along the perivascular space relative to adjacent fiber tracts. To ensure the robustness of the findings, Region of Interest (ROI) delineation was performed and validated using both manual anatomical delineation and JHU atlas-based methods. Statistical analyses included inter-group comparisons, Receiver Operating Characteristic (ROC) curves to assess predictive performance for PD-SCD, and partial correlation analyses between ALPS indices and cognitive domains. The DTI-ALPS indices were significantly lower in the PD-SCD group compared to both PD-NC and HC groups, exhibiting a significant stepwise decline (HC > PD-NC > PD-SCD). ROC analysis showed that the left ALPS index (AUC = 0.6503) and the mean ALPS index (AUC = 0.6452) had modest discriminatory performance in differentiating PD-SCD from PD-NC. Partial correlation analysis revealed that ALPS indices were specifically and significantly associated with attention and working memory deficits. Notably, the side of motor symptom onset in PD did not significantly influence ALPS values. High consistency was observed between the manual and atlas-based ROI methods. In this cross-sectional cohort, PD-SCD was associated with a lower DTI-ALPS index, and this diffusion alteration was related to attention and working-memory performance. These findings suggest that the DTI-ALPS index may serve as a potential diffusion-based marker for early cognitive risk stratification in PD; however, its precise biological basis and longitudinal significance require further investigation.