Association of the along‑perivascular space (ALPS) index and white matter volume with cognitive dysfunction in relapsing‑remitting multiple sclerosis patients

To investigate the relationship among the along perivascular space (ALPS) index, conventional neuroimaging markers, and cognitive impairment in patients with relapsing–remitting multiple sclerosis (RRMS). This study included 45 RRMS patients and 41 healthy controls (HC). All participants underwent clinical evaluation, magnetic resonance imaging (MRI), and comprehensive cognitive assessments. Cognitive function was assessed using the Brief International Cognitive Assessment for MS (BICAMS), which includes the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test–II (CVLT-II), and Brief Visuospatial Memory Test–Revised (BVMT-R). Additional tests evaluated attention, executive function, verbal fluency, and global cognition. Cognitive impairment was defined as a Z‑score ≤ -1.5 in at least two of the three BICAMS domains. Spearman correlation and multiple linear regression analyses were used to examine associations between neuroimaging metrics and cognitive scores in RRMS patients. Backward stepwise logistic regression was performed to identify variables independently associated with cognitive impairment. RRMS patients had a significantly lower ALPS index compared to HC (t = -2.225, q = 0.029). Within the RRMS group, patients with cognitive impairment showed further reductions in the ALPS index. Multiple linear regression confirmed that the ALPS index was significantly associated with Z‑scores of the Symbol Digit Modalities Test (SDMT; β = 0.415, q = 0.003), PASAT-3 s (Paced Auditory Serial Addition Test-3 s; β = 0.305, q = 0.037), PASAT-2 s (β = 0.429, q = 0.002) and Controlled Oral Word Association Test (COWA; β = 0.305, q = 0.044). In addition, a negative correlation was observed between white matter lesion number (WMLN) and the Z‑scores of COWA (β = -0.340, q = 0.013). In the backward stepwise logistic regression model, the ALPS index (OR = 0.044, 95% CI: 0.003–0.776, q = 0.033) and normalized white matter volume (nWMV; OR = 0.764, 95% CI: 0.599–0.975, q = 0.030) were retained as variables independently associated with cognitive impairment. Our study suggests that both a reduced ALPS index and lower nWMV are independently associated with cognitive impairment in RRMS. These findings implicate the combined roles of impaired interstitial fluid clearance and structural integrity in RRMS-related cognitive dysfunction. As a non-invasive MR metric, the ALPS index may serve as a potential complementary biomarker for assessing cognitive risk in RRMS.