Perivascular Spaces and Diffusion Tensor Imaging Analysis Along the Perivascular Space Show Distinct Associations with Aging and Alzheimer’s Disease

BACKGROUND AND PURPOSE: MRI-visible perivascular spaces (PVS) are structural findings on T2-weighted MRI, whereas diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) measures directional water diffusivity in deep white matter. We compared PVS burden and ALPS across young controls, elderly controls, and patients with Alzheimer's disease (AD). MATERIALS AND METHODS: This retrospective, institutional review board-approved study included an acquisition-harmonized cohort of 16 young controls, 22 elderly controls, and 32 patients with biomarker-confirmed AD, all with DTI acquired on the same 3T Siemens MAGNETOM Vida platform. Two blinded readers graded basal ganglia (BG) and centrum semiovale (CSO) PVS on 2D axial T2-weighted images. PVS and ALPS were compared across the 3 groups; age- and sex-adjusted regression evaluated the elderly-control versus AD difference. RESULTS: Interrater reliability was excellent (quadratic-weighted kappa = 0.873-0.929). Median combined PVS scores (range, 0-8) were 2.75, 5.00, and 4.75 in young, elderly controls, and AD, respectively (P < .001), with no elderly-control versus AD difference (P = .89). Median ALPS indices were 1.365, 1.235, and 1.102 (P < .001). In pairwise testing unadjusted for age or sex, the elderly-control versus AD ALPS difference did not reach statistical significance (P = .05). In age- and sex-adjusted regression, AD was associated with lower ALPS (beta = -0.080; 95% CI, -0.158 to -0.003; P = .04), and the association persisted after additional adjustment for combined PVS (beta = -0.082; P = .04). CONCLUSIONS: In a single-scanner, acquisition-harmonized cohort, MRI-visible PVS burden was predominantly associated with older age, whereas a modest AD-associated reduction in ALPS emerged after covariate adjustment. PVS grading and ALPS characterize different structural and diffusion features and should not be considered interchangeable. Longitudinal validation with higher-resolution diffusion imaging is needed to determine whether ALPS provides additional clinical value.