Methods in Neuroepidemiology
Vitamin D-Mentia: Randomized Clinical Trials Should Be the Next StepAnnweiler C. · Beauchet O.
Department of Internal Medicine and Geriatrics, Angers University Hospital; Angers University Memory Center; UPRES EA 2646, University of Angers, UNAM, Angers, France
Cédric Annweiler, MD, PhD
Department of Internal Medicine and Geriatrics, Angers University Hospital
FR–49933 Angers Cedex 9 (France)
Tel. +33 2 41 35 44 58
Do you have an account?
Hypovitaminosis D is highly prevalent in the elderly. Its possible role in the pathogenesis of Alzheimer’s disease (AD) is particularly important, as AD remains a public health concern with no current efficient treatment. Vitamin D administration could be a multitarget stabilizing treatment for AD since vitamin D simultaneously targets several factors leading to neurodegeneration through immunoregulatory, antioxidant and anti-ischemic actions, as well as the regulation of neurotrophic factors, acetylcholine neurotransmitter and clearance of amyloid beta peptide, and the avoidance of hyperparathyroidism. By preventing neuronal loss, the question is whether correcting hypovitaminosis D among older adults could also prevent AD-related cognitive decline. The cross-sectional associations between the vitamin D intakes – whether from diet, sun exposure or drug supplements – and cognition strengthened this hypothesis, but prevented the finding of a cause and effect link. Pre-post studies showed an improvement of cognition concomitant with the increase in 25-hydroxyvitamin D concentrations. One randomized trial found that supraphysiological doses of vitamin D were not better than physiological doses at improving cognition in AD. At this stage, only clinical trials testing vitamin D supplements versus placebo can further determine the impact of vitamin D administration on cognition and AD with higher levels of evidence.
© 2011 S. Karger AG, Basel
- Kalueff A-V, Tuohimaa P: Neurosteroid hormone vitamin D and its utility in clinical nutrition. Curr Opin Clin Nutr Metab Care 2007;10:12–19.
- Buell J-S, Dawson-Hughes B: Vitamin D and neurocognitive dysfunction: preventing ‘D’ecline? Mol Aspects Med 2008;29:415–422.
- Annweiler C, Schott A-M, Berrut G, et al: Vitamin D and ageing: neurological issues. Neuropsychobiology 2010;62:139–150.
- Holick M-F: Vitamin D deficiency. N Engl J Med 2007;357:266–281.
- Miller J-W: Vitamin D and cognitive function in older adults: are we concerned about vitamin D-mentia? Neurology 2010;74:13–15.
- McCann J-C, Ames B-N: Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction? FASEB J 2008;22:982–1001.
- Grant WB. Does vitamin D reduce the risk of dementia? J Alzheimers Dis 2009;17:151–159.
- Annweiler C, Allali G, Allain P, et al: Vitamin D and cognitive performance in adults: a systematic review. Eur J Neurol 2009;16:1083–1089.
- Annweiler C, Schott A-M, Allali G, et al: Association of vitamin D deficiency with cognitive impairment in older women: cross-sectional study. Neurology 2010;74:27–32.
- Slinin Y, Paudel M-L, Taylor B-C, et al: 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology 2010;74:33–41.
- Llewellyn D-J, Lang I-A, Langa K-M, et al: Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med 2010;170:1135–1141.
- Annweiler C, Fantino B, Le Gall D, et al: Severe vitamin D deficiency is associated with advanced-stage dementia amongst geriatric inpatients. J Am Geriatr Soc 2011;59:169–171.
- Sato Y, Asoh T, Oizumi K: High prevalence of vitamin D deficiency and reduced bone mass in elderly women with Alzheimer’s disease. Bone 1998;23:555–557.
- Evatt M-L, Delong M-R, Khazai N, et al: Prevalence of vitamin D insufficiency in patients with Parkinson disease and Alzheimer disease. Arch Neurol 2008;65:1348–1352.
- Buell J-S, Dawson-Hughes B, Scott T-M, et al: 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 2010;74:18–26.
- Llewellyn D-J, Lang I-A, Langa K-M, et al: Vitamin D and cognitive impairment in the elderly U.S. population. J Gerontol A Biol Sci Med Sci 2011;66:59–65.
- Colette F, Van der Linden M, Salmon E: Executive dysfunction in Alzheimer’s disease. Cortex 1999;35:57–72.
- Miyake A, Friedman N-P, Emerson M-J, et al: The unity and diversity of executive functions and their contributions to complex ‘frontal lobe’ tasks: a latent variable analysis. Cognit Psychol 2000;41:49–100.
- Buell J-S, Scott T-M, Dawson-Hughes B, et al: Vitamin D is associated with cognitive function in elders receiving home health services. J Gerontol A Biol Sci Med Sci 2009;64:888–895.
- Querfurth H-W, LaFerla F-M: Alzheimer’s disease. N Engl J Med 2010;362:329–344.
Sokolow S, Luu S-H, Vinters H-V, et al: Glutamatergic (VGLUT1) synapses are not lost in Alzheimer’s disease cerebral cortex, but preferentially accumulate amyloid-beta and p-tau pathology. Alzheimers Dement 2010;6:S243.
- Gouras G-K, Tampellini D, Takahashi R-H, et al: Intraneuronal beta-amyloid accumulation and synapse pathology in Alzheimer’s disease. Acta Neuropathol 2010;119:523–541.
- Ankarcrona M, Dypbukt J-M, Bonfoco E, et al: Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron 1995;15:961–973.
- Bonfoco E, Krainc D, Ankarcrona M, et al: Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci USA 1995;92:7162–7166.
- Aisen P-S: Pre-dementia Alzheimer’s trials: overview. J Nutr Health Aging 2010;14:294.
- Vellas B, Aisen P-S: Early Alzheimer’s trials: new developments. J Nutr Health Aging 2010;14:293.
- Lee D-M, Tajar A, Ulubaev A, et al: Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men. J Neurol Neurosurg Psychiatry 2009;80:722–729.
- Wilkins C-H, Birge S-J, Sheline Y-I, et al: Vitamin D deficiency is associated with worse cognitive performance and lower bone density in older African Americans. J Natl Med Assoc 2009;101:349–354.
- Seamans K-M, Hill T-R, Scully L, et al: Vitamin D status and measures of cognitive function in healthy older European adults. Eur J Clin Nutr 2010;64:1172–1178.
- Garcion E, Wion-Barbot N, Montero-Menei C-N, et al: New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 2002;13:100–105.
- Moore M-E, Piazza A, McCartney Y, Lynch MA: Evidence that vitamin D3 reverses age-related inflammatory changes in the rat hippocampus. Biochem Soc Trans 2005;33:573–577.
- Masoumi A, Goldenson B, Ghirmai S, et al: 1alpha,25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer’s disease patients. J Alzheimers Dis 2009;17:703–717.
- De Viragh P-A, Haglid K-G, Celio M-R: Parvalbumin increases in the caudate putamen of rats with vitamin D hypervitaminosis. Proc Natl Acad Sci USA 1989;86:3887–3890.
- Ibi M, Sawada H, Nakanishi M, et al: Protective effects of 1 alpha,25-(OH)(2)D(3) against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture. Neuropharmacology 2001;40:761–771.
- Brown J, Bianco J-I, McGrath J-J, et al: 1,25-Dihydroxyvitamin D-3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci Lett 2003;343:139–143.
- Wang Y, Chiang Y-H, Su T-P, et al: Vitamin D3 attenuates cortical infarction induced by middle cerebral arterial ligation in rats. Neuropharmacology 2000;39:873–880.
- Sonnenberg J, Luine V-N, Krey L-C, et al: 1,25-Dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activity in specific brain nuclei. Endocrinology 1986;118:1433–1439.
- Annweiler C, Le Gall D, Fantino B, et al: 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 2010;75:95.
- Souberbielle J-C, Prié D, Courbebaisse M, et al: Update on vitamin D and evaluation of vitamin D status. Ann Endocrinol (Paris) 2008;69:501–510.
- Vieth R: Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999;69:842–856.
- Hathcock J-N, Shao A, Vieth R, et al: Risk assessment for vitamin D. Am J Clin Nutr 2007;85:6–18.
- van Vliet P, Oleksik A-M, Mooijaart S-P, et al: APOE genotype modulates the effect of serum calcium levels on cognitive function in old age. Neurology 2009;72:821–828.
- Annweiler C, Montero-Odasso M, Schott AM, et al: Fall prevention and vitamin D in the elderly: an overview of the key role of the non-bone effects. J Neuroeng Rehabil 2010;7:50.
- Annweiler C, Schott A-M, Rolland Y, et al: Dietary intake of vitamin D and cognition in older women: a large population-based study. Neurology 2010;75:1810–1816.
- Rondanelli M, Trotti R, Opizzi A, et al: Relationship among nutritional status, pro/antioxidant balance and cognitive performance in a group of free-living healthy elderly. Minerva Med 2007;98:639–645.
- MacLaughlin J, Holick M-F: Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest 1985;76:1536–1538.
- Przybelski R, Agrawal S, Krueger D, et al: Rapid correction of low vitamin D status in nursing home residents. Osteoporos Int 2008;19:1621–1628.
- Stein M-S, Scherer S-C, Ladd K-S, et al: A randomized controlled trial of high-dose vitamin D2 followed by intranasal insulin in Alzheimer’s disease. J Alzheimers Dis 2011;26:477–484.
- Burne T-H, Johnston A-N, McGrath J-J, et al: Swimming behaviour and post-swimming activity in vitamin D receptor knockout mice. Brain Res Bull 2006;69:74–78.
- Kalueff A-V, Keisala T, Minasyan A, et al: Behavioural anomalies in mice evoked by ‘Tokyo’ disruption of the vitamin D receptor gene. Neurosci Res 2006;54:254–260.
Lai C-K, Yeung J-H, Mok V, et al: Special care units for dementia individuals with behavioural problems. Cochrane Database Syst Rev 2009;4:CD006470.
- Romagnoli E, Mascia M-L, Cipriani C, et al: Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab 2008;93:3015–3020.
- Ross A-C, Manson J-E, Abrams S-A, et al: The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011;96:53–58.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.