Vitamin D Status and Rates of Cognitive Decline in a Multiethnic Cohort of Older Adults | Dementia and Cognitive Impairment | JAMA Neurology | JAMA Network
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Committee to Review Dietary Reference Intakes for Vitamin D and Calcium, Institute of Medicine.  Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2010.
Forrest  KY, Stuhldreher  WL.  Prevalence and correlates of vitamin D deficiency in US adults.  Nutr Res. 2011;31(1):48-54.PubMedGoogle ScholarCrossref
Eyles  DW, Smith  S, Kinobe  R, Hewison  M, McGrath  JJ.  Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain.  J Chem Neuroanat. 2005;29(1):21-30.PubMedGoogle ScholarCrossref
Eyles  DW, Liu  PY, Josh  P, Cui  X.  Intracellular distribution of the vitamin D receptor in the brain: comparison with classic target tissues and redistribution with development.  Neuroscience. 2014;268:1-9.PubMedGoogle ScholarCrossref
Annweiler  C, Schott  AM, Berrut  G, Fantino  B, Beauchet  O.  Vitamin D-related changes in physical performance: a systematic review.  J Nutr Health Aging. 2009;13(10):893-898.PubMedGoogle ScholarCrossref
Annweiler  C, Dursun  E, Féron  F,  et al.  “Vitamin D and cognition in older adults”: updated international recommendations.  J Intern Med. 2015;277(1):45-57.PubMedGoogle ScholarCrossref
Littlejohns  TJ, Henley  WE, Lang  IA,  et al.  Vitamin D and the risk of dementia and Alzheimer disease.  Neurology. 2014;83(10):920-928.PubMedGoogle ScholarCrossref
Annweiler  C, Rolland  Y, Schott  AM,  et al.  Higher vitamin D dietary intake is associated with lower risk of Alzheimer’s disease: a 7-year follow-up.  J Gerontol A Biol Sci Med Sci. 2012;67(11):1205-1211.PubMedGoogle ScholarCrossref
Annweiler  C, Fantino  B, Schott  AM, Krolak-Salmon  P, Allali  G, Beauchet  O.  Vitamin D insufficiency and mild cognitive impairment: cross-sectional association.  Eur J Neurol. 2012;19(7):1023-1029.PubMedGoogle ScholarCrossref
Annweiler  C, Montero-Odasso  M, Llewellyn  DJ, Richard-Devantoy  S, Duque  G, Beauchet  O.  Meta-analysis of memory and executive dysfunctions in relation to vitamin D.  J Alzheimers Dis. 2013;37(1):147-171.PubMedGoogle Scholar
Llewellyn  DJ, Lang  IA, Langa  KM, Melzer  D.  Vitamin D and cognitive impairment in the elderly US population.  J Gerontol A Biol Sci Med Sci. 2011;66(1):59-65.PubMedGoogle ScholarCrossref
Llewellyn  DJ, Lang  IA, Langa  KM,  et al.  Vitamin D and risk of cognitive decline in elderly persons.  Arch Intern Med. 2010;170(13):1135-1141.PubMedGoogle ScholarCrossref
Luchsinger  JA, Reitz  C, Honig  LS, Tang  MX, Shea  S, Mayeux  R.  Aggregation of vascular risk factors and risk of incident Alzheimer disease.  Neurology. 2005;65(4):545-551.PubMedGoogle ScholarCrossref
Reitz  C, Tang  MX, Manly  J, Mayeux  R, Luchsinger  JA.  Hypertension and the risk of mild cognitive impairment.  Arch Neurol. 2007;64(12):1734-1740.PubMedGoogle ScholarCrossref
Whitmer  RA, Sidney  S, Selby  J, Johnston  SC, Yaffe  K.  Midlife cardiovascular risk factors and risk of dementia in late life.  Neurology. 2005;64(2):277-281.PubMedGoogle ScholarCrossref
Kivipelto  M, Ngandu  T, Laatikainen  T, Winblad  B, Soininen  H, Tuomilehto  J.  Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study.  Lancet Neurol. 2006;5(9):735-741.PubMedGoogle ScholarCrossref
Hinton  L, Carter  K, Reed  BR,  et al.  Recruitment of a community-based cohort for research on diversity and risk of dementia.  Alzheimer Dis Assoc Disord. 2010;24(3):234-241.PubMedGoogle Scholar
Morris  JC, Weintraub  S, Chui  HC,  et al.  The Uniform Data Set (UDS): clinical and cognitive variables and descriptive data from Alzheimer Disease Centers.  Alzheimer Dis Assoc Disord. 2006;20(4):210-216.PubMedGoogle ScholarCrossref
Weintraub  S, Salmon  D, Mercaldo  N,  et al.  The Alzheimer’s Disease Centers’ Uniform Data Set (UDS): the neuropsychologic test battery.  Alzheimer Dis Assoc Disord. 2009;23(2):91-101.PubMedGoogle ScholarCrossref
Morris  JC.  The Clinical Dementia Rating (CDR): current version and scoring rules.  Neurology. 1993;43(11):2412-2414.PubMedGoogle ScholarCrossref
American Psychiatric Association.  Diagnostic and Statistical Manual of Mental Disorders.3rd ed, revised. Washington, DC: American Psychiatric Association; 1987.
Mungas  D, Reed  BR, Tomaszewski Farias  S, DeCarli  C.  Criterion-referenced validity of a neuropsychological test battery: equivalent performance in elderly Hispanics and non-Hispanic whites.  J Int Neuropsychol Soc. 2005;11(5):620-630.PubMedGoogle ScholarCrossref
Mungas  D, Beckett  L, Harvey  D,  et al.  Heterogeneity of cognitive trajectories in diverse older persons.  Psychol Aging. 2010;25(3):606-619.PubMedGoogle ScholarCrossref
Mungas  D, Reed  BR, Marshall  SC, González  HM.  Development of psychometrically matched English and Spanish language neuropsychological tests for older persons.  Neuropsychology. 2000;14(2):209-223.PubMedGoogle ScholarCrossref
Mungas  D, Reed  BR, Crane  PK, Haan  MN, González  H.  Spanish and English Neuropsychological Assessment Scales (SENAS): further development and psychometric characteristics.  Psychol Assess. 2004;16(4):347-359.PubMedGoogle ScholarCrossref
Mungas  D, Reed  BR, Haan  MN, González  H.  Spanish and English Neuropsychological Assessment Scales: relationship to demographics, language, cognition, and independent function.  Neuropsychology. 2005;19(4):466-475.PubMedGoogle ScholarCrossref
Annweiler  C, Schott  AM, Allali  G,  et al.  Association of vitamin D deficiency with cognitive impairment in older women: cross-sectional study.  Neurology. 2010;74(1):27-32.PubMedGoogle ScholarCrossref
Elias  MF, Wolf  PA, D’Agostino  RB, Cobb  J, White  LR.  Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study.  Am J Epidemiol. 1993;138(6):353-364.PubMedGoogle Scholar
Elias  MF, Elias  PK, Robbins  MA, Wolf  PA, D’Agostino  RB. Cardiovascular risk factors and cognitive functioning: an epidemiological perspective. In: Waldstein  SR, Elias  MF, eds.  Neuropsychology of Cardiovascular Disease. Mahwah, NJ: Lawrence Erlbaum Associates; 2001:83-104.
Elias  MF, Sullivan  LM, D’Agostino  RB,  et al.  Framingham stroke risk profile and lowered cognitive performance.  Stroke. 2004;35(2):404-409.PubMedGoogle ScholarCrossref
Whitmer  RA, Gunderson  EP, Barrett-Connor  E, Quesenberry  CP  Jr, Yaffe  K.  Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study.  BMJ. 2005;330(7504):1360.PubMedGoogle ScholarCrossref
Early  DR, Widaman  KF, Harvey  D,  et al.  Demographic predictors of cognitive change in ethnically diverse older persons.  Psychol Aging. 2013;28(3):633-645.PubMedGoogle ScholarCrossref
US Census Bureau. Census quickfacts. Accessed August 13, 2013.
US Administration on Aging. A statistical profile of Hispanic older Americans aged 65+. Accessed August 13, 2013.
Haan  MN, Mungas  DM, Gonzalez  HM, Ortiz  TA, Acharya  A, Jagust  WJ.  Prevalence of dementia in older Latinos: the influence of type 2 diabetes mellitus, stroke and genetic factors.  J Am Geriatr Soc. 2003;51(2):169-177.PubMedGoogle ScholarCrossref
Luchsinger  JA, Reitz  C, Patel  B, Tang  MX, Manly  JJ, Mayeux  R.  Relation of diabetes to mild cognitive impairment.  Arch Neurol. 2007;64(4):570-575.PubMedGoogle ScholarCrossref
Cress  RD, Holly  EA.  Incidence of cutaneous melanoma among non-Hispanic whites, Hispanics, Asians, and blacks: an analysis of California Cancer Registry data, 1988-93.  Cancer Causes Control. 1997;8(2):246-252.PubMedGoogle ScholarCrossref
Holick  MF.  Vitamin D deficiency.  N Engl J Med. 2007;357(3):266-281.PubMedGoogle ScholarCrossref
Bouillon  R, Carmeliet  G, Daci  E, Segaert  S, Verstuyf  A.  Vitamin D metabolism and action.  Osteoporos Int. 1998;8(suppl 2):S13-S19.PubMedGoogle ScholarCrossref
Rostand  SG.  Ultraviolet light may contribute to geographic and racial blood pressure differences.  Hypertension. 1997;30(2, pt 1):150-156.PubMedGoogle ScholarCrossref
Rostand  SG.  Vitamin D, blood pressure, and African Americans: toward a unifying hypothesis.  Clin J Am Soc Nephrol. 2010;5(9):1697-1703.PubMedGoogle ScholarCrossref
Wang  TJ, Pencina  MJ, Booth  SL,  et al.  Vitamin D deficiency and risk of cardiovascular disease.  Circulation. 2008;117(4):503-511.PubMedGoogle ScholarCrossref
Schneider  JA, Arvanitakis  Z, Bang  W, Bennett  DA.  Mixed brain pathologies account for most dementia cases in community-dwelling older persons.  Neurology. 2007;69(24):2197-2204.PubMedGoogle ScholarCrossref
Afzal  S, Bojesen  SE, Nordestgaard  BG.  Reduced 25-hydroxyvitamin D and risk of Alzheimer’s disease and vascular dementia.  Alzheimers Dement. 2014;10(3):296-302.PubMedGoogle ScholarCrossref
Beydoun  MA, Gary  TL, Caballero  BH, Lawrence  RS, Cheskin  LJ, Wang  Y.  Ethnic differences in dairy and related nutrient consumption among US adults and their association with obesity, central obesity, and the metabolic syndrome.  Am J Clin Nutr. 2008;87(6):1914-1925.PubMedGoogle Scholar
Annweiler  C, Annweiler  T, Bartha  R, Herrmann  FR, Camicioli  R, Beauchet  O.  Vitamin D and white matter abnormalities in older adults: a cross-sectional neuroimaging study.  Eur J Neurol. 2014;21(12):1436-e95.PubMedGoogle ScholarCrossref
Hooshmand  B, Lökk  J, Solomon  A,  et al.  Vitamin D in relation to cognitive impairment, cerebrospinal fluid biomarkers, and brain volumes.  J Gerontol A Biol Sci Med Sci. 2014;69(9):1132-1138.PubMedGoogle ScholarCrossref
Annweiler  C, Annweiler  T, Montero-Odasso  M, Bartha  R, Beauchet  O.  Vitamin D and brain volumetric changes: systematic review and meta-analysis.  Maturitas. 2014;78(1):30-39.PubMedGoogle ScholarCrossref
Andreasen  N, Minthon  L, Vanmechelen  E,  et al.  Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer’s disease in patients with mild cognitive impairment.  Neurosci Lett. 1999;273(1):5-8.PubMedGoogle ScholarCrossref
Pericak-Vance  MA, Bass  MP, Yamaoka  LH,  et al.  Complete genomic screen in late-onset familial Alzheimer disease: evidence for a new locus on chromosome 12.  JAMA. 1997;278(15):1237-1241.PubMedGoogle ScholarCrossref
Gezen-Ak  D, Dursun  E, Ertan  T,  et al.  Association between vitamin D receptor gene polymorphism and Alzheimer’s disease.  Tohoku J Exp Med. 2007;212(3):275-282.PubMedGoogle ScholarCrossref
Lehmann  DJ, Refsum  H, Warden  DR, Medway  C, Wilcock  GK, Smith  AD.  The vitamin D receptor gene is associated with Alzheimer’s disease.  Neurosci Lett. 2011;504(2):79-82.PubMedGoogle ScholarCrossref
Wang  L, Hara  K, Van Baaren  JM,  et al.  Vitamin D receptor and Alzheimer’s disease: a genetic and functional study.  Neurobiol Aging. 2012;33(8):1844.e1-1844.e9.PubMedGoogle ScholarCrossref
Uitterlinden  AG, Fang  Y, Van Meurs  JB, Pols  HA, Van Leeuwen  JP.  Genetics and biology of vitamin D receptor polymorphisms.  Gene. 2004;338(2):143-156.PubMedGoogle ScholarCrossref
Touvier  M, Deschasaux  M, Montourcy  M,  et al.  Determinants of vitamin D status in Caucasian adults: influence of sun exposure, dietary intake, sociodemographic, lifestyle, anthropometric, and genetic factors.  J Invest Dermatol. 2015;135(2):378-388.PubMedGoogle ScholarCrossref
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    1 Comment for this article
    Sunlight is the major source of VitD and affect body, mind and intellect.
    Dr.Rajiv Kumar, Dr.Jagjit Singh. | Faculty, Department of Pharmacology, Government Medical College & Hospital Chandigarh 160030. India.
    Vitamin D (VitD), is the fat-soluble, steroid prohormone & sunshine vitamin. VitD has received increased attention due to the identification of extra-skeletal effect i.e beyond bone health. Vit D receptor (VDR) has been identified in skin, placenta, brain, pancreas, breast, prostate, colon cancer cells, and activated T cells. There are promising extra-skeletal therapeutic implications of Vitamin D beyond bone health, VitD has anticancer properties [1]. As per the Hindu Religion, Surya symbolizes the Sun God. The sun, source of light and energy for the entire solar system. Surya Namaskar (Salutations to the Sun) is experienced on three levels ? body, mind and intellect and exposure in sunlight is the major source of VitD [2]. Vitamin D is considered as a neurosteroid, the neuroprotective and immunomodulatory effects of VitD have been shown in experimental models, indicating the potential value in neurodegenerative and neuroimmune diseases [3]. Study has shown that VitD enhances mood in healthy subjects during winter [4] and results were consistent with the hypothesis that low VitD concentration is associated with depression [5]. VitD supplementation is effective in depression in adults [6]. However regarding cognitive function, well designed randomized controlled trials (RCTs) are needed to determine whether VitD supplementation is effective at preventing or treating Alzheimer's disease and dementia.

    1. KK Deeb, DL Trump, CS Johnson. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer. 2007;7(9):684-700.
    3. E Garcion , N Wion-Barbot , CN Montero-Menei , F Berger, D Wion. New clues about Vitamin D functions in the nervous system. Trends Endocrinol Metab. 2002 Apr;13(3):100-5.
    4. AT Lansdowne, SC Provost. Vitamin D3 enhances mood in healthy subjects during winter. Psychopharmacology (Berl). 1998 ;135(4):319-23.
    5. RE Anglin , Z Samaan , SD Walter, SD McDonald. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013 ;202:100-7.
    6. Li Guowei , M Lawrence, S Zainab , Z Shiyuan, DA Jonathan, P Alexandra, T Lehana. Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol.Syst Rev. 2013; 2: 64.
    Original Investigation
    November 2015

    Vitamin D Status and Rates of Cognitive Decline in a Multiethnic Cohort of Older Adults

    Author Affiliations
    • 1Department of Nutritional Sciences, Rutgers University, New Brunswick, New Jersey
    • 2Department of Medical Pathology and Laboratory Medicine, University of California, Davis
    • 3Division of Biostatistics, Department of Public Health Sciences, University of California, Davis
    • 4Department of Neurology, University of California, Davis
    JAMA Neurol. 2015;72(11):1295-1303. doi:10.1001/jamaneurol.2015.2115

    Importance  Vitamin D (VitD) deficiency is associated with brain structural abnormalities, cognitive decline, and incident dementia.

    Objective  To assess associations between VitD status and trajectories of change in subdomains of cognitive function in a cohort of ethnically diverse older adults.

    Design, Setting, and Participants  Longitudinal multiethnic cohort study of 382 participants in an outpatient clinic enrolled between February 2002 and August 2010 with baseline assessment and yearly follow-up visits. Serum 25-hydroxyvitamin D (25-OHD) was measured, with VitD status defined as the following: deficient, less than 12 ng/mL (to convert to nanomoles per liter, multiply by 2.496); insufficient, 12 to less than 20 ng/mL; adequate, 20 to less than 50 ng/mL; or high, 50 ng/mL or higher. Subdomains of cognitive function were assessed using the Spanish and English Neuropsychological Assessment Scales. Associations were evaluated between 25-OHD levels (as continuous and categorical [deficient, insufficient, or adequate]) and trajectories of cognitive decline.

    Main Outcomes and Measures  Serum 25-OHD levels, cognitive function, and associations between 25-OHD levels and trajectories of cognitive decline.

    Results  Participants (N = 382 at baseline) had a mean (SD) age of 75.5 (7.0) years; 61.8% were women; and 41.4% were white, 29.6% African American, 25.1% Hispanic, and 3.9% other race/ethnicity. Diagnosis at enrollment included 17.5% with dementia, 32.7% with mild cognitive impairment, and 49.5% cognitively normal. The mean (SD) 25-OHD level was 19.2 (11.7) ng/mL, with 26.2% of participants being VitD deficient and 35.1% insufficient. The mean (SD) 25-OHD levels were significantly lower for African American and Hispanic participants compared with white participants (17.9 [15.8] and 17.2 [8.4] vs 21.7 [10.0] ng/mL, respectively; P < .001 for both). The mean (SD) 25-OHD levels were similarly lower in the dementia group compared with the mild cognitive impairment and cognitively normal groups (16.2 [9.4] vs 20.0 [10.3] and 19.7 [13.1] ng/mL, respectively; P = .006). The mean (SD) follow-up was 4.8 (2.5) years. Rates of decline in episodic memory and executive function among VitD-deficient (episodic memory: β = −0.04 [SE = 0.02], P = .049; executive function: β = −0.05 [SE = 0.02], P = .01) and VitD-insufficient (episodic memory: β = −0.06 [SE = 0.02], P < .001; executive function: β = −0.04 [SE = 0.02], P = .008) participants were greater than those with adequate status after controlling for age, sex, education, ethnicity, body mass index, season of blood draw, vascular risk, and apolipoprotein E4 genotype. Vitamin D status was not significantly associated with decline in semantic memory or visuospatial ability. Exclusion of participants with dementia did not substantially affect the associations between VitD status and rates of cognitive decline.

    Conclusions and Relevance  Low VitD status was associated with accelerated decline in cognitive function domains in ethnically diverse older adults, including African American and Hispanic individuals who exhibited a high prevalence of VitD insufficiency or deficiency. It remains to be determined whether VitD supplementation slows cognitive decline.