Effect of Vitamin D Replacement on Cognition in Multiple Sclerosis Patients

Hala Darwish, Ribal Haddad, Sahar Osman, Stephanie Ghassan, Bassem Yamout, Hani Tamim, Samia Khoury, Hala Darwish, Ribal Haddad, Sahar Osman, Stephanie Ghassan, Bassem Yamout, Hani Tamim, Samia Khoury

Abstract

Multiple Sclerosis is associated with deficient serum 25 hydroxyvitamin D (25 (OH)D) level and cognitive impairment. The aim of this study is to evaluate cognitive performance in MS patients with deficient 25 (OH)D (<25 ng/ml) compared to patients with sufficient levels (>35 ng/ml), then to evaluate the change in cognitive performance after 3 months of vitamin D3 oral replacement. Eighty-eight MS patients with relapsing remitting and clinically isolated type of MS, older than 18 years treated with interferon beta were enrolled. Cognitive testing was performed at baseline and at 3 months using the Montreal Cognitive Assessment (MoCA), Stroop, Symbol Digit Modalities (SDMT) and Brief Visuospatial Memory Test (BVMT-R). Serum 25 (OH)D was measured at baseline and at the end of the study. Vitamin D3 replacement improved the MS patients' cognitive performance after 3 months on the MoCA and BVMT-Delayed Recall (DR). Sufficient serum 25 (OH)D level predicted better cognitive performance on the BVMT-DR at baseline (β: 1.74, p: <0.008) and 3 months (β: 1.93, p: <0.01) after adjusting for all measured confounding variables. Vitamin D3 replacement could improve cognitive performance in MS patients and make a significant difference in the patient's quality of life.

Conflict of interest statement

We disclose that S.K. and H.D. have received research grants from Novartis. H.D. furthermore received honoraria for lectures from Novartis, travel awards from Novartis, Merck and Genzyme, and Research grants from MENACTRIMS. B.Y. received honoraria for lectures from Bayer, Genzyme, Merck-Serono, Novartis, Genpharm, Biogen, research grants from Bayer, Merck-Serono, Novartis, Biogen, Pfizer and he serves on the Advisory board with Honoraria from Bayer, Novartis, Merck-Serono, Biogen, Genzyme, Genpharm.

Figures

Figure 1
Figure 1
Flow Diagram of the subjects enrollment from recruitment through study completion.

References

    1. Ascherio A. & Munger K. L. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann Neurol 61, 504–513 (2007).
    1. Ascherio A. & Marrie R. A. Vitamin D in MS: a vitamin for 4 seasons. Neurology 79, 208–210 (2012).
    1. Ascherio A. et al.. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol 71, 306–314 (2014).
    1. Fitzgerald K. C. et al.. Association of Vitamin D Levels With Multiple Sclerosis Activity and Progression in Patients Receiving Interferon Beta-1b. JAMA neurology 72, 1458–1465 (2015).
    1. Joshi S. et al.. 1,25-dihydroxyvitamin D(3) ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol Cell Biol 31, 3653–3669 (2011).
    1. Smolders J., Moen S. M., Damoiseaux J., Huitinga I. & Holmoy T. Vitamin D in the healthy and inflamed central nervous system: access and function. J Neurol Sci 311, 37–43 (2011).
    1. Smolders J., Muris A. H. & Damoiseaux J. Immunomodulation by vitamin D in multiple sclerosis: More than IL-17. J Neuroimmunol 292, 79–80 (2016).
    1. Correale J., Ysrraelit M. C. & Gaitan M. I. Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain: a journal of neurology 132, 1146–1160 (2009).
    1. Mouhieddine T. H. et al.. Risk factors for multiple sclerosis and associations with anti-EBV antibody titers. Clin Immunol 158, 59–66 (2015).
    1. Amato M. P. et al.. Treatment of cognitive impairment in multiple sclerosis: position paper. J Neurol 260, 1452–1468 (2013).
    1. Amato M. P. et al.. Cognitive reserve and cortical atrophy in multiple sclerosis: a longitudinal study. Neurology 80, 1728–1733 (2013).
    1. Amato M. P., Zipoli V. & Portaccio E. Cognitive changes in multiple sclerosis. Expert Rev Neurother 8, 1585–1596 (2008).
    1. Llewellyn D. J., Lang I. A., Langa K. M. & Melzer D. Vitamin D and cognitive impairment in the elderly US population. J Gerontol A Biol Sci Med Sci 66, 59–65 (2011).
    1. Llewellyn D. J., Langa K. M. & Lang I. A. Serum 25-hydroxyvitamin D concentration and cognitive impairment. J Geriatr Psychiatry Neurol 22, 188–195 (2009).
    1. Darwish H. et al.. Serum 25-hydroxyvitamin D predicts cognitive performance in adults. Neuropsychiatr Dis Treat 11, 2217–2223 (2015).
    1. Eyles D. W., Liu P. Y., Josh P. & Cui X. Intracellular distribution of the vitamin D receptor in the brain: comparison with classic target tissues and redistribution with development. Neuroscience 268, 1–9 (2014).
    1. Eyles D. W., Smith S., Kinobe R., Hewison M. & McGrath J. J. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 29, 21–30 (2005).
    1. Balion C. et al.. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology 79, 1397–1405 (2012).
    1. Annweiler C. et al.. ‘Vitamin D and cognition in older adults’: updated international recommendations. J Intern Med 277, 45–57 (2015).
    1. Schwid S. R., Goodman A. D., Weinstein A., McDermott M. P. & Johnson K. P. Cognitive function in relapsing multiple sclerosis: minimal changes in a 10-year clinical trial. J Neurol Sci 255, 57–63 (2007).
    1. Bergendal G., Fredrikson S. & Almkvist O. Selective decline in information processing in subgroups of multiple sclerosis: an 8-year longitudinal study. Eur Neurol 57, 193–202 (2007).
    1. Piras M. R. et al.. Longitudinal study of cognitive dysfunction in multiple sclerosis: neuropsychological, neuroradiological, and neurophysiological findings. Journal of Neurology, Neurosurgery & Psychiatry 74, 878–885 (2003).
    1. Tam J. W. & Schmitter-Edgecombe M. The Role of Processing Speed in the Brief Visuospatial Memory Test–Revised. The Clinical Neuropsychologist 27, 962–972 (2013).
    1. Kalueff A. V., Lou Y. R., Laaksi I. & Tuohimaa P. Increased anxiety in mice lacking vitamin D receptor gene. Neuroreport 15, 1271–1274 (2004).
    1. Armstrong D. J. et al.. Vitamin D deficiency is associated with anxiety and depression in fibromyalgia. Clin Rheumatol 26, 551–554 (2007).
    1. Ballard C., Rowan E., Stephens S., Kalaria R. & Kenny R. A. Prospective follow-up study between 3 and 15 months after stroke: improvements and decline in cognitive function among dementia-free stroke survivors >75 years of age. Stroke 34, 2440–2444 (2003).
    1. Krupp L. B. et al.. Donepezil improved memory in multiple sclerosis in a randomized clinical trial. Neurology 63, 1579–1585 (2004).
    1. Krupp L. B. et al.. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis. Neurology 76, 1500–1507 (2011).
    1. O’Brien A. R., Chiaravalloti N., Goverover Y. & Deluca J. Evidenced-based cognitive rehabilitation for persons with multiple sclerosis: a review of the literature. Arch Phys Med Rehabil 89, 761–769 (2008).
    1. Polman C. H. et al.. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Annals of neurology 69, 292–302 (2011).
    1. Mahfoud Z. et al.. The Arabic validation of Hopkins Symptoms Checklist-25 against MINI in a disadvantaged suburb of Beirut, Lebanon. The International Journal of Educational and Psychological Assessment (TIJEPA) 13, 17–33 (2013).
    1. CDC. Behavioral risk factor surveillance system survey questionnaire. Atlanta, Georgia: US Department of Health and Human Services, Centers for Disease Control and Prevention (2009).
    1. Rahman T. T. & El Gaafary M. M. Montreal Cognitive Assessment Arabic version: reliability and validity prevalence of mild cognitive impairment among elderly attending geriatric clubs in Cairo. Geriatr Gerontol Int 9, 54–61 (2009).
    1. Al-Ghatani A. M., Obonsawin M. C., Binshaig B. A. & Al-Moutaery K. R. Saudi normative data for the Wisconsin Card Sorting test, Stroop test, Test of Non-verbal Intelligence-3, Picture Completion and Vocabulary (subtest of the Wechsler Adult Intelligence Scale-Revised). Neurosciences (Riyadh) 16, 29–41 (2011).
    1. Niccolai C. et al.. A comparison of the brief international cognitive assessment for multiple sclerosis and the brief repeatable battery in multiple sclerosis patients. BMC Neurol 15, 204 (2015).
    1. Abdel-Wareth L. et al.. Total vitamin D assay comparison of the Roche Diagnostics “Vitamin D total” electrochemiluminescence protein binding assay with the Chromsystems HPLC method in a population with both D2 and D3 forms of vitamin D. Nutrients 5, 971–980 (2013).

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