Low serum 25‑hydroxy-vitamin D levels are associated with cognitive impairment in multiple sclerosis

Background: Cognitive impairment frequently affects people with multiple sclerosis (MS). Low vitamin D has been associated with cognitive dysfunction in different neurodegenerative diseases, and, in MS, with motor disability and disease activity. We aim to investigate associations between vitamin D and cognitive status in MS. Methods: In this cross-sectional study, we included 181 MS patients, recruited consecutively at the MS Unit of the Policlinico Federico II University Hospital of Naples, Italy, between January and April 2022, with serum 25‑hydroxy (25-OH) vitamin D measurements using Chemiluminescence-ImmunoAssay, and cognitive assessment using the Brief International Cognitive Assessment for MS (BICAMS), which includes Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II) and Brief Visuospatial Memory Test-Revised (BVMT-R). We collected demographics (age, sex, education), and clinical variables (disease duration, disease subtype, expanded disability status scale (EDSS), disease modifying treatment, relapses in previous 12 months, vitamin D supplementation, comorbidities). For a subset of patients (n = 41, 23.2% of the total sample), we collected Beck Depression Inventory-II, Beck Anxiety Inventory, and Modified Fatigue Impact Scale. Results: At univariable linear regression models, serum 25-OH-vitamin D levels were 0.9 ng/mL higher for each unit increase of SDMT adjusted scores (Coeff=0.93; 95%CI=0.81, 1.04; p<0.01), 0.7 ng/mL higher for each unit increase of CVLT-II adjusted scores (Coeff=0.68; 95%CI=0.53, 0.83; p<0. 01), 0.6 ng/mL higher for each unit increase of BVMT-R adjusted scores (Coeff=0.58; 95%CI=0.43, 0.73; p<0.01), -9.63 ng/mL lower for each impaired BICAMS test (Coeff=-9.63; 95%CI=-11.48, -7.79; p<0.01), and -2.2 ng/mL lower for each unit increase of EDSS (Coeff=-2.16; 95%CI=-3.57, -0.75; p<0.01). At multivariable linear regression models, we confirmed associations between 25-OH-vitamin D and EDSS (Coeff=-2.09; 95%CI=-4.45, -0.43; p<0.01), SDMT (Coeff=0.75; 95%CI=0.60, 0.90; p<0.01), and CVLT-II (Coeff=0.14; 95%CI=0.01, 0.28; p = 0. 04). Results remained unchanged when including depression, anxiety and fatigue scores. Conclusions: Lower serum 25-OH-vitamin D was associated with worse cognitive function in MS. Future studies should consider longitudinal variations in cognitive function in relation to vitamin D supplementation.