Cerebrovascular risk factors impact on brain atrophy and DTI-ALPS decrease in neuromyelitis optica spectrum disorder

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy where disability is largely relapse-driven. Cerebrovascular risk factors (cVRFs) may exacerbate astrocytic and small-vessel injury. Therefore, we investigated their impact on MRI damage and disability in NMOSD. Methods: Twenty-eight aquaporin 4 immunoglobulin G-positive NMOSD patients and 56 age- and sex-matched healthy controls (HC) underwent 3T brain and cervical MRI, cVRF and neurological assessment, including the Expanded Disability Status Scale (EDSS). Brain T2-hyperintense white matter lesion volume (WMLV), normalized global and regional volumes, normal-appearing WM (NAWM) fractional anisotropy (FA) and mean diffusivity (MD), diffusion tensor imaging analysis along the perivascular spaces (DTI-ALPS) index, spinal cord lesion volume (SCLV) and normalized cross-sectional area (nCSA) were quantified. Results: cVRF were present in 57% of NMOSD and 39% of HC, with smoking being the most frequent (all FDR-p = 0.734). Compared to HC, NMOSD showed significantly higher brain WMLV and SCLV, lower normalized brain (NBV), and deep gray matter volume (nDGMV) (all FDR-p ≤ 0.030). Significant diagnosis × cVRF interactions were found for nDGMV and DTI-ALPS (all FDR-p ≤ 0.038). In NMOSD, higher EDSS significantly correlated with lower DTI-ALPS (r = – 0.47, FDR-p = 0.048) and higher SCLV (r = 0.54, FDR-p = 030). Moderation analysis revealed that cVRFs significantly amplified the association between DTI-ALPS and disability (FDR-p = 0.045). Conclusions: cVRFs amplify CNS damage and the clinical impact of impaired neurofluid dynamics in NMOSD, suggesting convergent vascular and astrocytic injury.