Vitamin D and cognition: an update of the current evidence.

The active form vitamin D is a seco-steroid with multiple neurotrophic and neuroprotective functions in the central nervous system. Robust evidence from studies in animals suggests that vitamin D deficiency may impair brain physiological functioning causing anatomical and behavioral adverse effects. On the other hand, vitamin D has been found to be protective against biological processes associated with Alzheimer's disease and cognition, including amyloid-β deposition, inflammation, calcium homeostasis, and corticosteroid-induced perturbations in cortical areas and the hippocampus. Human studies that examined the relationship between vitamin D status and cognitive function have provided inconclusive results. The majority of cross-sectional and longitudinal studies suggest a potentially protective association, whereas results from clinical trials are mostly negative, or at best, controversial. We review these studies in humans, with particular emphasis on randomized and observational prospective ones.

[1]  C. Annweiler,et al.  Combination of memantine and vitamin D prevents axon degeneration induced by amyloid-beta and glutamate , 2014, Neurobiology of Aging.

[2]  I. Fogelman,et al.  The relationship between pro-resorptive inflammatory cytokines and the effect of high dose vitamin D supplementation on their circulating concentrations. , 2013, International immunopharmacology.

[3]  R. Bals,et al.  Impact of Vitamin D on Amyloid Precursor Protein Processing and Amyloid-β Peptide Degradation in Alzheimer's Disease , 2013, Neurodegenerative Diseases.

[4]  E. Hyppönen,et al.  25-Hydroxyvitamin D and cognitive performance in mid-life , 2013, British Journal of Nutrition.

[5]  Y. Schouw,et al.  The association between vitamin D and cognition: A systematic review , 2013, Ageing Research Reviews.

[6]  S. Yılmazer,et al.  Vitamin D inquiry in hippocampal neurons: consequences of vitamin D-VDR pathway disruption on calcium channel and the vitamin D requirement , 2013, Neurological Sciences.

[7]  V. Sundararajan,et al.  Vitamin d deficiency impacts on expression of toll-like receptor-2 and cytokine profile: a pilot study , 2013, Journal of Translational Medicine.

[8]  J. Jakobsen,et al.  Vitamin D in plants: a review of occurrence, analysis, and biosynthesis , 2013, Front. Plant Sci..

[9]  M. Frye,et al.  Hypovitaminosis D in psychiatric inpatients: clinical correlation with depressive symptoms, cognitive impairment, and prescribing practices. , 2013, Psychosomatics.

[10]  C. Annweiler,et al.  Vitamin D concentration and lateral cerebral ventricle volume in older adults. , 2013, Molecular nutrition & food research.

[11]  J. Manson,et al.  Calcium and Vitamin D Supplementation and Cognitive Impairment in the Women's Health Initiative , 2012, Journal of the American Geriatrics Society.

[12]  K. Yaffe,et al.  Association between serum 25(OH) vitamin D and the risk of cognitive decline in older women. , 2012, The journals of gerontology. Series A, Biological sciences and medical sciences.

[13]  J. Kaye,et al.  Serum vitamin d concentrations are associated with falling and cognitive function in older adults , 2012, The journal of nutrition, health & aging.

[14]  Cynthia Balion,et al.  Vitamin D, cognition, and dementia , 2012, Neurology.

[15]  J. Gilbert,et al.  Vitamin D receptor and Alzheimer's disease: a genetic and functional study , 2012, Neurobiology of Aging.

[16]  C. Annweiler,et al.  Vitamin D insufficiency and mild cognitive impairment: cross‐sectional association , 2012, European journal of neurology.

[17]  E. Feskens,et al.  Associations of 25-hydroxyvitamin D with fasting glucose, fasting insulin, dementia and depression in European elderly: the SENECA study , 2012, European Journal of Nutrition.

[18]  G. Cowin,et al.  Neuroanatomy and psychomimetic-induced locomotion in C57BL/6J and 129/X1SvJ mice exposed to developmental vitamin D deficiency , 2012, Behavioural Brain Research.

[19]  D. Lawlor,et al.  Association of serum 25-hydroxyvitamin D3 and D2 with academic performance in childhood: findings from a prospective birth cohort , 2012, Journal of Epidemiology & Community Health.

[20]  Kerry Jones,et al.  Vitamin D and cognitive function , 2012, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[21]  H. Brodaty,et al.  Relationships between serum vitamin D levels, neuromuscular and neuropsychological function and falls in older men and women , 2012, Osteoporosis International.

[22]  H. Brenner,et al.  Vitamin D and cognitive functioning in the elderly population in Germany , 2012, Experimental Gerontology.

[23]  C. Annweiler,et al.  Serum Vitamin D Deficiency as a Predictor of Incident Non-Alzheimer Dementias: A 7-Year Longitudinal Study , 2012, Dementia and Geriatric Cognitive Disorders.

[24]  M. Bellgrove,et al.  Effects of Vitamin D Supplementation on Cognitive and Emotional Functioning in Young Adults – A Randomised Controlled Trial , 2011, PloS one.

[25]  A. Smith,et al.  The vitamin D receptor gene is associated with Alzheimer's disease , 2011, Neuroscience Letters.

[26]  Toshiko Tanaka,et al.  Genome-wide association study of circulating retinol levels , 2011, Human molecular genetics.

[27]  T. Terasaki,et al.  1α,25-Dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-β peptide(1-40) from mouse brain across the blood-brain barrier , 2011, Fluids and Barriers of the CNS.

[28]  J. Woo,et al.  Association between serum 25-hydroxyvitamin D and psychological health in older Chinese men in a cohort study. , 2011, Journal of affective disorders.

[29]  D. Lawlor,et al.  The Association of Serum Ionized Calcium and Vitamin D With Adult Cognitive Performance , 2011, Epidemiology.

[30]  C. Annweiler,et al.  Dietary intake of vitamin D and cognition in older women , 2010, Neurology.

[31]  A. Polito,et al.  Vitamin D status and measures of cognitive function in healthy older European adults , 2010, European Journal of Clinical Nutrition.

[32]  Daniel L. Koller,et al.  Common genetic determinants of vitamin D insufficiency: a genome-wide association study , 2010, The Lancet.

[33]  D. Melzer,et al.  Vitamin D and risk of cognitive decline in elderly persons. , 2010, Archives of internal medicine.

[34]  M. Jäättelä,et al.  Autophagy as a basis for the health-promoting effects of vitamin D. , 2010, Trends in molecular medicine.

[35]  R. Hayes,et al.  Circulating 25-Hydroxyvitamin D and Risk of Pancreatic Cancer , 2010, American journal of epidemiology.

[36]  J. Simpson,et al.  Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. , 2010, JAMA.

[37]  C. Annweiler,et al.  Association of vitamin D deficiency with cognitive impairment in older women , 2010, Neurology.

[38]  M. Folstein,et al.  25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services , 2010, Neurology.

[39]  J. Cauley,et al.  25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men , 2010, Neurology.

[40]  I. Lang,et al.  Serum 25-Hydroxyvitamin D Concentration and Cognitive Impairment , 2009, Journal of geriatric psychiatry and neurology.

[41]  R. D'Agostino,et al.  Genetic and non-genetic correlates of vitamins K and D , 2009, European Journal of Clinical Nutrition.

[42]  J. Jolles,et al.  VDR gene variants associate with cognitive function and depressive symptoms in old age , 2009, Neurobiology of Aging.

[43]  Michael J. Pencina,et al.  Vitamin D Deficiency and Risk of Cardiovascular Disease , 2008, Circulation.

[44]  G. Mcneill,et al.  Nutritional status and subsequent all-cause mortality in men and women aged 75 years or over living in the community , 2007, British Journal of Nutrition.

[45]  N. Porter,et al.  Chronic 1α,25-(OH)2vitamin D3 treatment reduces Ca2+-mediated hippocampal biomarkers of aging , 2006 .

[46]  M. Visser,et al.  Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission. , 2006, The American journal of clinical nutrition.

[47]  H. Gronemeyer,et al.  Cross‐talk of vitamin D and glucocorticoids in hippocampal cells , 2006, Journal of neurochemistry.

[48]  A. Lin,et al.  Antioxidative Effect of Vitamin D3 on Zinc‐Induced Oxidative Stress in CNS , 2005, Annals of the New York Academy of Sciences.

[49]  J. McGrath,et al.  Distribution of the Vitamin D receptor and 1α-hydroxylase in human brain , 2005, Journal of Chemical Neuroanatomy.

[50]  M. Holick Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. , 2004, The American journal of clinical nutrition.

[51]  T. Strandberg,et al.  Predictors of cognitive decline and mortality of aged people over a 10-year period. , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[52]  D. Eyles,et al.  1,25-Dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons , 2003, Neuroscience Letters.

[53]  A. Mackay-Sim,et al.  Vitamin d3 and brain development , 2003, Neuroscience.

[54]  C. Montero-Menei,et al.  Vitamin D3 inhibits proinflammatory cytokines and nitric oxide production by the EOC13 microglial cell line , 2003, Journal of neuroscience research.

[55]  Philip W. Landfield,et al.  Vitamin D Hormone Confers Neuroprotection in Parallel with Downregulation of L-Type Calcium Channel Expression in Hippocampal Neurons , 2001, The Journal of Neuroscience.

[56]  R. Vieth,et al.  Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. , 1999, The American journal of clinical nutrition.

[57]  P. Brachet,et al.  Synthesis of 1,25‐dihydroxyvitamin D3 by rat brain macrophages in vitro , 1994, Journal of neuroscience research.

[58]  H. DeLuca The vitamin D story: a collaborative effort of basic science and clinical medicine 1 , 1988, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[59]  K. Altemus,et al.  Behavioral correlates of vitamin D deficiency , 1987, Physiology & Behavior.

[60]  J. D. Perry,et al.  Using Activities of Daily Living Assessments to Measure the Effectiveness of Vitamin D Supplements in Elderly Long-Stay Patients , 1987 .

[61]  W. Pardridge,et al.  Restricted Transport of Vitamin D and A Derivatives Through the Rat Blood‐Brain Barrier , 1985, Journal of neurochemistry.

[62]  R. Cohen,et al.  Do vitamin D supplements improve the physical capabilities of elderly hospital patients? , 1985, Age and ageing.

[63]  H. Richter,et al.  25-hydroxyvitamin D, 24, 25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D in human cerebrospinal fluid , 1984, Klinische Wochenschrift.

[64]  C. Annweiler,et al.  Low serum vitamin D concentrations in Alzheimer's disease: a systematic review and meta-analysis. , 2013, Journal of Alzheimer's disease : JAD.

[65]  S. Yılmazer,et al.  A new mechanism for amyloid-β induction of iNOS: vitamin D-VDR pathway disruption. , 2013, Journal of Alzheimer's disease : JAD.

[66]  C. Annweiler,et al.  Meta-analysis of memory and executive dysfunctions in relation to vitamin D. , 2013, Journal of Alzheimer's disease : JAD.

[67]  T. Grodzicki,et al.  25-hydroxyvitamin D and physical and cognitive performance in older people with chronic conditions. , 2012, Polskie Archiwum Medycyny Wewnetrznej.

[68]  S. Yılmazer,et al.  A novel perspective for Alzheimer's disease: vitamin D receptor suppression by amyloid-β and preventing the amyloid-β induced alterations by vitamin D in cortical neurons. , 2011, Journal of Alzheimer's disease : JAD.

[69]  M. Stein,et al.  A randomized controlled trial of high-dose vitamin D2 followed by intranasal insulin in Alzheimer's disease. , 2011, Journal of Alzheimer's disease : JAD.

[70]  D. Lawlor,et al.  The association of circulating 25-hydroxyvitamin D and calcium with cognitive performance in adolescents: cross-sectional study using data from the third National Health and Nutrition Examination Survey. , 2011, Paediatric and perinatal epidemiology.

[71]  C. Annweiler,et al.  Extraskeletal effects of vitamin D: facts, uncertainties, and controversies. , 2011, Joint, bone, spine : revue du rhumatisme.