Longitudinal Effect of Vitamin D3 Replacement on Cognitive Performance and MRI Markers in Multiple Sclerosis Patients

Background: Multiple Sclerosis is strongly associated with low serum 25 hydroxy-vitamin-D (25(OH)D) and impaired cognitive performance. In our previous research, participants with low serum 25OHD levels showed significant improvements in visuo-spatial memory delayed recall after 3 months of vitamin D3 supplementation. In addition, serum 25(OH)D was significantly associated with this memory function at baseline and at 3 months. Therefore, the aim of this proposed study is 1) to evaluate the long-term effects 6 and 12 months of high (50,000 IU weekly then 10,000 IU weekly) compared to low dose (800 IU daily) vitamin D3 replacement on cognitive function in MS, and 2) to correlate it with the MRI brain measurements of the hippocampus and the frontal cortex volumes, as well as brain parenchymal fraction, and cerebellum. The investigators will then explore these MRI measures in MS patients with deficient 25(OH)D levels at baseline and at 12 months, and correlate it with their cognitive performance. Methods: This is a longitudinal single blind randomized trial to test the effects of high compared to low dose vitamin D3 supplementation on cognitive performance at 6 and 12 months, and MRI measures of 12 months duration. A cognitive assessment battery, comprised of the Montreal Cognitive Assessment (only at baseline), Stroop, Symbol Digit Modalities Test, Brief Visual Memory Test, and Verbal Memory Test in Arabic, will be administered at baseline, 6 and 12 months. Related clinical data and information on depression and anxiety, lifestyle, and food sources of vitamin D and sun exposure among other variables will also be collected. Expected results: MS patients with serum 25(OH)D deficiency who receive high dose vitamin D3 supplementation will demonstrate decreased cognitive impairment at 6 and 12 months post supplementation when compared to those who received low vitamin D3 dose and to their pre-supplementation status. The MRI findings are expected to be associated with cognitive performance at baseline, and serum 25(OH)D levels at baseline, and 12 months.