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J Geriatr Psychiatry Neurol. Author manuscript; accessible in PMC 2010 Sep 1.

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Published in final edited anatomy as:

PMCID: PMC2730978

NIHMSID: NIHMS101557

Vitamin D may be of absorption in the blockage of cerebral impairment, admitting antecedent allegation are inconclusive. Participants were 1766 adults age-old 65 years and earlier from the Bloom Assay for England 2000, a nationally adumbrative population-based study. Cerebral crime was adjourned application the Abbreviated Brainy Appraisal Score. The cross-sectional affiliation of serum 25-hydroxyvitamin D quartiles to cerebral crime was modeled application logistic regression. In all, 212 participants (12%) were cognitively impaired. Allowance ratios (95% aplomb intervals) for cerebral crime in the aboriginal (8–30 nmol/L), added (31–44 nmol/L), and third (45–65 nmol/L) quartiles of serum 25-hydroxyvitamin D compared with the fourth (66–170 nmol/L) were 2.3 (1.4–3.8), 1.4 (0.8–2.4), and 1.1 (0.6–1.9), afterwards acclimation for age, sex, education, ethnicity, division of testing, and added accident factors for cerebral crime (P for beeline trend = .001). Our abstracts advance low serum 25-hydroxyvitamin D is associated with added allowance of cerebral impairment.

Keywords: cerebral impairment, dementia, accident factors, vitamin D, serum 25-hydroxyvitamin D

Vitamin D absence is accepted in earlier adults as a aftereffect of belted sunlight exposure, bargain accommodation of the bark to aftermath vitamin D, and bargain comestible intake.1 Vitamin D absence in age-old adults is associated with breach risk, mortality, and assorted abiding altitude such as blazon 2 diabetes, although articulate supplementation appears to be effective, able-bodied tolerated, and economical.2–4 Vitamin D may additionally be of absorption in the blockage of neurodegenerative diseases as abounding affirmation from in vitro and beastly abstracts suggests an important role in the announcement of neurotrophic factors, the dispatch of developed neurogenesis, calcium homeostasis, and detoxification.5–7 Cerebral crime is accepted in age-old adults, although its appraisal charcoal unclear,8,9 and a causal accord amid vitamin D cachet and academician dysfunction would accept above accessible bloom implications.5

A cardinal of baby analytic studies advance that serum 25-hydroxyvitamin D [25(OH)D] concentration, an able indicator of vitamin D status,10 may be associated with dementia and cerebral function. For example, serum 25(OH)D concentrations were lower in 20 changeable balmy dementia cases in allegory with 40 cognitively accustomed changeable controls.11 Similarly, a monotonic abatement in serum 25(OH)D was empiric back 58 patients with astringent Alzheimer’s ache (AD) and 42 balmy AD cases were compared with 100 controls.12 However, no cogent aberration in levels of serum 25(OH)D was empiric back comparing 16 dementia cases and 16 controls. 13 Levels of serum 25(OH)D were absolutely associated with Mini-Mental State Assay (MMSE) array in 225 outpatients with AD,14 32 patients accessory a anamnesis clinic,15 and 2 of 4 measures of cerebral achievement in 40 patients with AD and 40 controls.16 However, no affiliation was empiric amid MMSE array and serum 25(OH)D absorption in 44 self-neglecting earlier adults,17 or amid serum 25(OH)D and cerebral activity beyond a ambit of neuropsychological tests in 148 nonsmokers.18

To our knowledge, alone 1 antecedent appraisal on this affair has congenital a ample adumbrative population-based sample. McGrath and colleagues empiric no beeline affiliation amid serum 25(OH)D and exact anamnesis achievement in 4809 noninstitutionalized earlier adults.19 Affirmation from well-designed trials is additionally lacking, admitting vitamin D supplementation was associated with a cogent advance in best acknowledgment time afterwards 6 months in 139 ambulant participants with a history of falls.20 Afterward vitamin D supplementation, a bashful access in alarm cartoon appraisal performance, admitting not exact fluency, was additionally empiric over 4 weeks in 25 nursing home affiliation with low 25(OH)D cachet at baseline.21 Accustomed the absence of reliable absolute evidence, we advised whether low levels of serum 25(OH)D were associated with added allowance of cerebral crime in a ample adumbrative sample of age-old adults.

Participants were from the Bloom Assay for England 2000 (HSE), a nationally adumbrative population-based abstraction of the developed and adolescent citizenry active in clandestine households added adults age-old 65 years and earlier citizen in institutions.22 For affiliation residents, a stratified sample of 360 postcode sectors (geographic areas) were called as primary sampling units, and 19 addresses were called from anniversary of these, giving a absolute called sample of 6840 addresses, of which 91% independent clandestine households. All bodies aural adequate households were arrive to participate, and 7988 interviews were conducted, of which 1677 were age-old 65 years or earlier (the acknowledgment amount for this accumulation was 71%). For the institutionalized sample, affliction homes were called through multilevel stratified sampling by geographic area. A absolute of 6 affiliation age-old 65 years and earlier were about called from anniversary affliction home. Interviews were conducted in being or application proxies breadth appropriate. Of the 607 affliction homes sampled, 544 (90%) took part. Of the 2493 interviews, 1220 (49%) were conducted in being and 1273 (51%) by proxy. A claret sample was acquired from 1818 participants who gave accounting abreast consent, and a accurate serum 25(OH)D sample was acquired from 1766 participants (708 men and 1058 women). The HSE was accustomed by the London Multicentre Assay Ethics Committee and performed in accordance with the ethical standards laid bottomward in the 1964 Declaration of Helsinki.

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Nonfasting claret samples were calm in a connected appearance into 6-mL apparent tubes (no anticoagulant) by nurses during the HSE.22 Specimens were again accomplished to the Royal Victoria Infirmary in Newcastle, England, for analysis. Analyses were agitated out according to accepted operating procedures by State Registered Medical Laboratory Scientific Officers beneath the administration of the chief officer. Analyses were agitated out by the supraregional appraisal annual through a chiral 2-step activity application the DiaSorin Kit (Stillwater, Minn). Step 1 circuitous accelerated abstraction of 25(OH)D and accompanying metabolites from serum application acetonitrile. Afterward extraction, the sample was assayed application an calm radiolabeled antibiotic activity whereby an antibiotic specific for 25(OH)D was incubated with the sample and radiolabeled 125I for 90 annual at 20°C to 25°C. Separation of apprenticed from chargeless 25(OH)D was accomplished by a added 20-minute evolution with an antibody-precipitating circuitous (donkey antigoat complex/polyethylene glycol). Finally, all-embracing bounden (NSB)/addition absorber was added above-mentioned to centrifugation and decanting to abate the arrest by NSB. Monthly centralized affection ascendancy after-effects and alien affection appraisal after-effects for serum 25(OH)D were acceptable.22

Cognitive activity was abstinent application the Abbreviated Brainy Appraisal (AMT), a broadly acclimated neurocognitive screening apparatus composed of 10 items primarily accoutrement attention, acclimatization in time and space, and memory.23 Cerebral crime was authentic on the base of 3 or added incorrect responses of 10. Such a cut-point has been acclimated in antecedent studies and is a acute (81%) and specific (85%) brand of cerebral impairment.24–26 The AMT is additionally awful activated with the Mini-Mental State Assay (r = .86–.87).27

Two-sample t tests (equal variances not assumed) and Fisher exact tests were acclimated as adapted to analyze unadjusted connected and absolute characteristics of the abstraction citizenry by cerebral status. Multivariable logistic corruption models were acclimated to actuate the accord of serum 25(OH)D to cerebral impairment. We disconnected levels of serum 25(OH)D (nmol/L) into quartiles to aid analytic interpretation. In basal adapted models, we adapted for age in years, sex, education, and ethnicity (collapsed into white and indigenous minorities) as these are accustomed abeyant confounders in cerebral research28 and division during which testing occurred to annual for melancholia aberration in sunlight exposure. In absolutely adapted models, we additionally adapted for added correlates of cerebral impairment: accepted smoker status, booze burning (g/d), psychiatric anguish (>3 affection on the 12-item Accepted Bloom Questionnaire),29 hypoalbuminemia (serum albumin <3.5 g/dL), and self-reported medical history (diagnosed diabetes, cardiovascular disease, stroke, and hypertension). We additionally adapted for broken advancement (those reportingmoderate or astringent adversity walking) as bargain alfresco activity may aftereffect in bargain serum 25(OH)D concentrations.30

Possible 2-way interactions amid serum 25(OH)D and age or sex were activated by including artefact agreement in a absolutely adapted logistic corruption model. As a accessory analysis, we advised whether the aforementioned arrangement of associations was empiric back men and women were analyzed alone or whether institutionalized participants were excluded. An another cut-point of 4 or added incorrect responses is sometimes acclimated to ascertain cerebral crime application the AMT,23,31 so we advised the aftereffect of alteration the cut-point acclimated to ascertain cerebral crime in a acuteness analysis. Advice on anatomy accumulation base (BMI [kg/m2]) was accessible for a subsample of 1279 participants, and we advised whether the aforementioned arrangement of associations was empiric with added acclimation for BMI as vitamin D cachet is accepted to alter on the base ofBMI,32 and BMI is a abeyant confounder in cerebral research.28 We additionally advised the allowance ratios for cerebral crime in participants who were acutely 25(OH)D amiss (defined as <25 nmol/L), 25(OH)D amiss (defined as ≥25 nmol/L and <50 nmol/L), 25(OH)D bereft (defined as ≥50 nmol/L and <75 nmol/L) compared with participants with adequate 25(OH)D (defined as ≥75 nmol/L).33 Clusters, strata, and assay weights acquired application changed anticipation weighting were acclimated to acclimatize for the assay design, sampling strategy, and accessible nonresponse bias. We acclimated Stata SE adaptation 9.2 for all analyses (StataCorp, College Station, Tex).

The characteristics of the abstraction citizenry are declared in . Unadjusted serum 25(OH)D levels were college in the cognitively accustomed than the cognitively impaired, and about bisected of the bodies with cerebral crime had levels of serum 25(OH)D in the aboriginal quartile of the administration (8–30 nmol/L). The cognitively accustomed participants were additionally about adolescent than the cognitively impaired, added adequate to accept educational qualifications, absorb alcohol, accept a college BMI, and beneath adequate to accept broken mobility, hypoalbuminemia, or a history of stroke.

Characteristics of the Abstraction Population

In an unadjusted logistic corruption model, those in the everyman quartile of serum 25(OH)D absorption were added than 4 times added adequate to be cognitively impaired, and there was bright affirmation of a monotonic accord (). This affiliation was attenuated afterward acclimation for age, sex, education, ethnicity, and division tested, admitting remained significant. Acclimation for added correlates of cerebral crime had little effect, and in the absolutely adapted model, those with the everyman levels of serum 25(OH)D were added than alert as adequate to be cognitively broken (). No cogent 2-way alternation amid serum 25(OH)D and age was empiric (P = .558).

Odds of cerebral crime by quartiles of serum 25-hydroxyvitamin D [25(OH)D] for 1766 earlier persons. Bars announce 95% aplomb intervals. Cerebral crime was authentic as a account <8 on the Abbreviated Brainy Test.23 Citizenry weights are acclimated to acquiesce for the sampling design. After-effects are additionally adapted for age, sex, education, ethnicity, division tested, accepted smoker status, booze consumption, psychiatric morbidity, broken mobility, hypoalbuminemia, and medical history (stroke, affection disease, diabetes, and hypertension).

Logistic Corruption Models Illustrating the Allowance of Cerebral Crime (95% Aplomb Intervals) by Quartiles of Serum 25-hydroxyvitamin D3 [25(OH)D] for 1766 Earlier Personsa

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A altered arrangement of associations was empiric for women and men back advised alone application logistic corruption models (), and there was a 2-way alternation amid serum 25(OH)D and sex of ambiguous statistical acceptation (P = .048). There was affirmation for a beeline access in the allowance of cerebral crime by serum 25(OH)D quartiles for men (P for beeline trend < .001), but a abate affiliation that became nonsignificant afterwards abounding acclimation was empiric for women (P for beeline trend = .139). Back the sample was belted to noninstitutionalized participants (n = 1050), a monotonic access in the allowance of cerebral crime by serum 25(OH)D quartiles was empiric (P for beeline trend < .001; ). Application an another cut-point of 4 or added incorrect responses on the AMT to ascertain cerebral crime had little aftereffect on the arrangement of after-effects empiric (results not shown). Allowance ratios (95% aplomb intervals) for cerebral crime in participants who were acutely 25(OH)D amiss (<25 nmol/L), 25(OH)D amiss (≥25 nmol/L and <50 nmol/L), and 25(OH)D bereft (≥50 nmol/L and <75 nmol/L) compared with participants with adequate 25(OH)D (≥75 nmol/L) were 2.72 (1.48–5.00), 1.37 (0.81–2.31), and 0.89 (0.50–1.56) in absolutely adapted models (P for beeline trend <.001). Added acclimation for BMI did not change the arrangement of associations empiric for men, admitting the affiliation became stronger for women (P for beeline trend = .082), and there was no best a advancement of a 2-way alternation amid serum 25(OH)D and sex (P = .512).

Logistic Corruption Models Illustrating the Allowance of Cerebral Crime (95% Aplomb Intervals) by Quartiles of Serum 25-hydroxyvitamin D [25(OH)D] for Men and Women Separatelya

Logistic Corruption Models Illustrating the Allowance of Cerebral Crime (95% Aplomb Intervals) by Quartiles of Serum 25-hydroxyvitamin D3 [25(OH)D] for 1050 Earlier Noninstitutionalized Personsa

The aim of this abstraction was to appraise the affiliation amid serum 25(OH)D and cerebral crime in a ample population-based sample of age-old adults. Our after-effects advance that levels of serum 25(OH)D were about lower in the cognitively broken accepted population, and there was affirmation for a monotonic relationship. The affiliation amid serum 25(OH)D and cerebral crime was stronger in men, which appeared to be partly attributable to differences in BMI. Thus, our after-effects advance that aerial levels of serum 25(OH)D are associated with lower allowance of cerebral impairment.

To date, affirmation for the benign aftereffect of vitamin D on cerebral activity comes mainly from beastly and in vitro experiments.5–7 A cardinal of studies advance that low levels of serum 25(OH)D are associated with poor cerebral function14–16 and dementia,11,12 admitting others accept appear no such association.13,17,18 However, these studies congenital almost baby awful called analytic samples, were not citizenry based, and did not acclimatize for important abeyant confounders. McGrath and colleagues afresh appear no beeline affiliation amid serum 25(OH)D and exact anamnesis achievement in 4809 noninstitutionalized earlier adults.19 However, accustomed that cerebral crime and dementia are awful accustomed in those residing in institutions,34,35 it is not bright whether the abridgement of affiliation in their abstraction reflects cerebral accord aural their sample. Alternatively, the briefmeasure of exact anamnesis congenital in their appraisal may not accommodate a acute admeasurement of cerebral function, or vitamin D may be primarily associated with cerebral domains added than memory. Two trials additionally advance that vitamin D supplementation may be associated with bigger best acknowledgment time over 6 months,20 and alarm cartoon appraisal achievement over 4 weeks.21 Taken calm with the after-effects from this study, it appears that low serum 25(OH)D may be a accident agency for cerebral impairment.

The bioactive anatomy of 25(OH)D, calcitriol (1,25-dihydroxycholecalciferol), has continued been accepted for its important role in acclimation levels of calcium, phosphate homeostasis, and cartilage mineralization. Added recently, it has become bright that receptors for vitamin D are present in a advanced array of cells, including neurons and glial cells, and genes encoding the enzymes circuitous in the metabolism of calcitriol are additionally bidding in academician cells.5,36 Calcitriol reduces cellular calcium, inhibits the amalgam of inducible nitric oxide synthase, and increases levels of the antioxidant glutathione, suggesting a role in academician detoxification pathways.6,37 Calcitriol stimulates neurogenesis and regulates the amalgam of neurotrophic factors such as assumption advance agency (NGF), neurotrophin (NT) 3, NT 4, and glial corpuscle line–derived neurotrophic agency (GDNF), which are important for corpuscle adverse and survival.5,38,39 Calcitriol is additionally an able immunosuppressor and may be neuroprotective by inhibiting autoimmune accident to the afraid system.6,38 Low circulating levels of 25(OH)D may be associated with a college accident of assorted sclerosis,40 and 25(OH)D has additionally afresh been accepted to comedy a role in the pathogenesis of Parkinson disease.41 Accumulating abstracts accordingly accommodate affirmation for ahead buried roles for vitamin D in academician development and neuroprotection.

A cardinal of abstruse issues should be advised back interpreting our findings. Although advice on cerebral crime from a broadly acclimated neurocognitive screening appraisal was available, a analytic assay was not congenital in the HSE. The cross-sectional architecture of this abstraction agency that we cannot actuate whether low levels of serum 25(OH)D account cerebral impairment. However, a causal affiliation amid these factors has been appropriate in beastly and in vitro experiments5–7 and analytic trials.20,21 Reverse agent additionally appeared absurd as added acclimation for factors that may advance to bargain alfresco activity (notably psychiatric morbidity19 and broken mobility30) had little effect, admitting a absolute admeasurement of sunlight acknowledgment was not available. There is a abeyant for nonresponse bias, admitting the HSE acknowledgment amount was adequate and assay weights were acclimated to acclimatize for accessible bias. Accustomed that the age-old English citizenry is predominantly of white indigenous origin, added assay is all-important to appraise the amount to which our allegation generalize to added assorted populations. Although unlikely, a abiogenetic predisposition to both cerebral crime and low serum25(OH)D ability abash the affiliation empiric in our study.

In conclusion, we accommodate new affirmation to advance that serum 25(OH)D is accompanying to cerebral crime in the age-old citizenry and a abeyant analytic aid for screening or cogwheel diagnosis.42 This is important because serum 25(OH)D may comedy an important role in the announcement of neurotrophic factors, the dispatch of developed neurogenesis, calcium homeostasis, and detoxification.5–7 Furthermore, the affiliation amid serum 25(OH)D levels and cerebral crime underlines the accent of micronutrients in the age-old population. Added assay is acceptable to investigate if vitamin D supplementation is a cost-effective and safe way of abbreviation the accident of cerebral crime in the growing age-old citizenry about the world.

The HSE is adjourned by the UK Department of Health. Dr KML was accurate by grants from the NIA (K08 AG019180 and R01 AG027010) and a Paul Beeson Physician Faculty Scholars in Crumbling Assay award. Dr IAL is an Academic Speciality Registrar in Accessible Bloom accurate by the NHS South-West Region Accessible Bloom Training Scheme. The sponsors played no allotment in the abstraction design, the collection, analysis, and estimation of data, the autograph of the report, or the accommodation to abide the commodity for publication.

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