Distinct Patterns of Perivascular Diffusivity and Choroid Plexus Volume in De Novo Parkinson's Disease and Type 2 Diabetes.
Background Alterations in perivascular fluid dynamics have been implicated in Parkinson's disease (PD) and metabolic disorders such as type 2 diabetes mellitus (T2DM). However, the relative contributions of neurodegenerative and metabolic conditions to functional perivascular water diffusivity versus structural neurofluid markers remain to be elucidated. Objectives To investigate the differences in perivascular water diffusivity and structural neurofluid markers using diffusion tensor image-analysis along the perivascular space (DTI-ALPS), perivascular space (PVS) burden, and choroid plexus volume (CPV) in PD and T2DM. Methods Consecutive patients with de novo PD and disease controls were included. Subjects were classified into four groups according to PD and T2DM status and matched for age and sex. The ALPS-index was derived from DTI, whereas PVS burden and CPV were quantified on three-dimensional T1-weighted images and normalized to intracranial volume. Results A total of 127 subjects were included. The ALPS-index differed significantly among the four groups (P < 0.001), with both PD groups demonstrating significantly lower values than control groups, irrespective of T2DM status. Within the PD cohort, longer disease duration and older age were independently associated with lower ALPS-index values. CPV also differed significantly across groups (P = 0.006) with higher values observed only in controls with T2DM, while PVS burden did not differ significantly. Conclusions In early-stage PD, impaired perivascular diffusivity was associated primarily with neurodegeneration, and no significant additive effect of T2DM was detected. Conversely, the increase in normalized CPV associated with T2DM was observed only in controls and not in PD, suggesting that metabolic and neurodegenerative conditions may differentially influence neurofluid markers.