Vitamin D in adults: update on testing and supplementation

Hypovitaminosis D, a frequent condition in adults, is accompanied by adverse skeletal and non-skeletal events. The objective of the present article was to propose an update on the indications and use of vitamin D testing and supplementation in adults. Among healthy middle-aged adults, the serum 25-hydroxyvitamin D (25(OH)D) target concentration is 50 nmol/L. Natural intakes (sun exposure and diet) are sufficient, and there is no indication for systematic blood test or supplementation. In middle-aged adults who are either sick or dependent or frail, natural intakes are generally insufficient but should be encouraged. In this population, the loading phase of the supplementation targets a 25(OH)D concentration of 75 nmol/L, and the pattern of supplementation (200,000 to 400,000 IU orally over 2 months) depends on the measure of circulating 25(OH)D (which is not reimbursed outside the scope defined by the French national authority for health). In adults over 65 years of age, the loading phase of the supplementation should be systematic and targets a concentration of 75 nmol/L (pattern of 300,000 IU orally over 3 months). Regardless of age, the loading phase should be followed by a long-term maintenance phase of supplementation to maintain the 25(OH)D concentration above the target. A measure of serum 25(OH)D is useful after 9 months of supplementation to adjust the frequency or dosage of supplements if necessary

Alzheimer's disease - input of vitamin D with mEmantine assay (AD-IDEA trial): study protocol for a randomized controlled trial

BACKGROUND: Current treatments for Alzheimer\u27s disease and related disorders (ADRD) are symptomatic and can only temporarily slow down ADRD. Future possibilities of care rely on multi-target drugs therapies that address simultaneously several pathophysiological processes leading to neurodegeneration. We hypothesized that the combination of memantine with vitamin D could be neuroprotective in ADRD, thereby limiting neuronal loss and cognitive decline. The aim of this trial is to compare the effect after 24 weeks of the oral intake of vitamin D3 (cholecalciferol) with the effect of a placebo on the change of cognitive performance in patients suffering from moderate ADRD and receiving memantine. METHODS: The AD-IDEA Trial is a unicentre, double-blind, randomized, placebo-controlled, intent-to-treat, superiority trial. Patients aged 60 years and older presenting with moderate ADRD (i.e., Mini-Mental State Examination [MMSE] score between 10-20), hypovitaminosis D (i.e., serum 25-hydroxyvitamin D [25OHD] < 30 ng/mL), normocalcemia (i.e., serum calcium < 2.65 mmol/L) and receiving no antidementia treatment at time of inclusion are being recruited. All participants receive memantine 20 mg once daily -titrated in 5 mg increments over 4 weeks- and each one is randomized to one of the two treatment options: either cholecalciferol (one 100,000 IU drinking vial every 4 weeks) or placebo (administered at the same pace). One hundred and twenty participants are being recruited and treatment continues for 24 weeks. Primary outcome measure is change in cognitive performance using Alzheimer\u27s Disease Assessment Scale-cognition score. Secondary outcomes are changes in other cognitive scores (MMSE, Frontal Assessment Battery, Trail Making Test parts A and B), change in functional performance (Activities of Daily Living scale, and 4-item Instrumental Activities of Daily Living scale), posture and gait (Timed Up & Go, Five Time Sit-to-Stand, spatio-temporal analysis of walking), as well as the between-groups comparison of compliance to treatment and tolerance. These outcomes are assessed at baseline, 12 and 24 weeks, together with the serum concentrations of 25OHD, calcium and parathyroid hormone. DISCUSSION: The combination of memantine plus vitamin D may represent a new multi-target therapeutic class for the treatment of ADRD. The AD-IDEA Trial seeks to provide evidence on its efficacy in limiting cognitive and functional declines in ADRD. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01409694

Motor phenotype of decline in cognitive performance among community-dwellers without dementia: Population-based study and meta-analysis

Background: Decline in cognitive performance is associated with gait deterioration. Our objectives were: 1) to determine, from an original study in older community-dwellers without diagnosis of dementia, which gait parameters, among slower gait speed, higher stride time variability (STV) and Timed Up & Go test (TUG) delta time, were most strongly associated with lower performance in two cognitive domains (i.e., episodic memory and executive function); and 2) to quantitatively synthesize, with a systematic review and meta-analysis, the association between gait performance and cognitive decline (i.e., mild cognitive impairment (MCI) and dementia). Methods: Based on a cross-sectional design, 934 older community-dwellers without dementia (mean6standard deviation, 70.3 64.9years; 52.1% female) were recruited. A score at 5 on the Short Mini-Mental State Examination defined low episodic memory performance. Low executive performance was defined by clock-drawing test errors. STV and gait speed were measured using GAITRite system. TUG delta time was calculated as the difference between the times needed to perform and to imagine the TUG. Then, a systematic Medline search was conducted in November 2013 using the Medical Subject Heading terms "Delirium," "Dementia," "Amnestic," "Cognitive disorders" combined with "Gait" OR "Gait disorders, Neurologic" and "Variability." Findings: A total of 294 (31.5%) participants presented decline in cognitive performance. Higher STV, higher TUG delta time, and slower gait speed were associated with decline in episodic memory and executive performances (all P-values <0.001). The highest magnitude of association was found for higher STV (effect size = -0.74 [95% Confidence Interval (CI): -1.05;- 0.43], among participants combining of decline in episodic memory and in executive performances). Meta-analysis underscored that higher STV represented a gait biomarker in patients with MCI (effect size = 0.48 [95% CI: 0.30;0.65]) and dementia (effect size = 1.06 [95% CI: 0.40;1.72]). Conclusion: Higher STV appears to be a motor phenotype of cognitive decline. © 2014 Beauchet et al

Extraskeletal effects of vitamin D: Facts, uncertainties, and controversies

Vitamin D was long viewed as a hormone acting chiefly to regulate calcium-phosphate metabolism and bone mineralization. Over the last decade, however, basic science and clinical researchers have produced a bewildering amount of information on the extraskeletal effects of vitamin D. This article is a review of the clinical and biological actions of vitamin D including effects on the immune system, auto-immune diseases, infections, cancer, metabolic syndrome, fall risk, cognitive function, and muscle function

Les effets extra-osseux de la vitamine D : faits, questions et controverses

La vitamine D a été longtemps considérée comme une hormone utile pour réguler le métabolisme phosphocalcique et la minéralisation osseuse. Depuis dix ans, la progression des connaissances fondamentales et cliniques sur son influence pluritissulaire est vertigineuse. Les auteurs passent en revue les effets biologique et clinique de la vitamine D en particulier sur le système immunitaire, les maladies auto-immunes, les infections, le cancer, le syndrome métabolique, le risque de chute, les fonctions cognitives et le fonctionnement musculaire

Motor imagery of gait: A new way to detect mild cognitive impairment?

Objectives. 1) To measure and compare the time required to perform (pTUG) and the time required to imagine (iTUG) the Timed Up & Go (TUG), and the time difference between these two tasks (i.e., TUG delta time) in older adults with cognitive decline (i.e., mild cognitive impairment (MCI) and mild-to-moderate Alzheimer disease and related disorders (ADRD)) and in cognitively healthy individuals (CHI); and 2) to examine any association between the TUG delta time and a cognitive status. Methods. Sixty-six participants (24 CHI, 23 individuals with MCI, and 19 individuals with ADRD) were recruited in this cross-sectional study. The mean and standard deviation of the pTUG and iTUG completion times and the TUG delta time, as well as age, gender, and Mini-Mental State Examination (MMSE) scores were used as outcomes. Participants were separated into three groups based on the tertilization of TUG delta time: lowest (52.2%; n = 22, worst performance). Results: Fewer CHI were in the group exhibiting the highest tertile of TUG delta time compared to individuals with lowest and intermediate TUG delta times (p = 0.013). Being in the highest tertile of the TUG delta time was associated with cognitive decline in the unadjusted model (p = 0.012 for MCI, and p = 0.021 for mild-to-moderate ADRD). In the multivariate models, this association remained significant only for individuals with MCI (p = 0.019 while adjusting for age and gender; p = 0.047 while adjusting for age, gender, and MMSE score; p = 0.012 for the stepwise backward model). Conclusions: Our results provide the first evidence that motor imagery of gait may be used as a biomarker of MCI in older adults. © 2014 Beauchet et al.; licensee BioMed Central Ltd

Profile of French community-dwelling older adults supplemented with vitamin D: findings and lessons

INTRODUCTION: The vast majority of older French adults exhibit some degree of hypovitaminosis D. The objective of this cross-sectional study was to determine the rate and the reasons for vitamin D prescription among older French adult community dwellers. METHODS: Vitamin D supplementation was systematically assessed among 1876 French community dwellers aged ≥ 65 years. Theoretical indications for vitamin D supplementation were collected, ie, the causes of hypovitaminosis D (older age, male gender, kidney failure, undernutrition, polymorbidity) or its clinical complications (vertebral or non-vertebral fractures, gait disturbances, history of falls, muscle weakness, and cognitive impairment). RESULTS: In total, 13.8% of the subjects (n=258) had vitamin D supplementation. They were more often malnourished (P=0.002), exhibited polymorbidity (P&lt;0.001) and muscle weakness (P&lt;0.001), and had a history of vertebral fractures (P&lt;0.001), non-vertebral fractures (P&lt;0.001), and accidental falls (P&lt;0.001). Vitamin D supplementation was explained by the number of complications of hypovitaminosis D (odds ratio [OR]=1.61, P&lt;0.001) including vertebral fractures (adjusted OR=1.49, P=0.007), non-vertebral fractures (adjusted OR=1.74, P=0.026), accidental falls (adjusted OR=1.44, P=0.015), and muscle weakness (adjusted OR=3.96, P&lt;0.001), but not by the number of causes of hypovitaminosis D (P=0.464). CONCLUSION: Even if vitamin D supplementation is selected well for appropriate patients, the rate of supplementation remains insufficient in France, and probably comes too late, ie, at the stage of complications of hypovitaminosis D. These findings should encourage physicians to supplement vitamin D more often and sooner in their elderly patients

High parathyroid hormone, but not low vitamin D concentrations, expose elderly inpatients to hypertension

AIM: Serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) concentrations might contribute to blood pressure (BP) levels. Mixed results in previous literature could be due to the failure to consider both these hormones concurrently, despite their long-known relationship. Our objective was to examine the association of serum intact PTH and 25OHD concentrations with BP levels amongst older inpatients, while accounting for each other. METHODS: The participants were 284 Caucasian older inpatients with no suspicion of primary hyperparathyroidism (mean age 85.87 ± 5.90 years; 65.8% female) admitted to the geriatric acute care unit of Angers University Hospital, France. They were divided into two groups according to the existence of hypertension (i.e. systolic blood pressure [SBP] &gt;140 mmHg, or diastolic blood pressure [DBP] &gt;90 mmHg). Age, sex, numbers of chronic diseases and of drugs taken daily, use of antihypertensive or corticosteroid drugs and of calcium supplements/vitamin D, thyroid-stimulating hormone and albumin concentrations, creatinine clearance, and season tested were used as covariables. RESULTS: Hypertensive participants (n=106) had higher intact PTH concentrations than normotensive patients (P=0.044). There was a positive linear association of BP with intact PTH concentrations (adjusted β=0.08, P=0.015 for SBP; adjusted β=0.05, P=0.044 for DBP), but not with vitamin D. Serum intact PTH concentration, unlike 25OHD, was associated with hypertension (adjusted OR 1.01, P=0.038). CONCLUSIONS: Irrespective of 25OHD, PTH was associated with hypertension by increasing both SBP and DBP

\u27Vitamin D and cognition in older adults\u27: updated international recommendations.

BACKGROUND: Hypovitaminosis D, a condition that is highly prevalent in older adults aged 65 years and above, is associated with brain changes and dementia. Given the rapidly accumulating and complex contribution of the literature in the field of vitamin D and cognition, clear guidance is needed for researchers and clinicians. METHODS: International experts met at an invitational summit on \u27Vitamin D and Cognition in Older Adults\u27. Based on previous reports and expert opinion, the task force focused on key questions relating to the role of vitamin D in Alzheimer\u27s disease and related disorders. Each question was discussed and voted using a Delphi-like approach. RESULTS: The experts reached an agreement that hypovitaminosis D increases the risk of cognitive decline and dementia in older adults and may alter the clinical presentation as a consequence of related comorbidities; however, at present, vitamin D level should not be used as a diagnostic or prognostic biomarker of Alzheimer\u27s disease due to lack of specificity and insufficient evidence. This population should be screened for hypovitaminosis D because of its high prevalence and should receive supplementation, if necessary; but this advice was not specific to cognition. During the debate, the possibility of \u27critical periods\u27 during which vitamin D may have its greatest impact on the brain was addressed; whether hypovitaminosis D influences cognition actively through deleterious effects and/or passively by loss of neuroprotection was also considered. CONCLUSIONS: The international task force agreed on five overarching principles related to vitamin D and cognition in older adults. Several areas of uncertainty remain, and it will be necessary to revise the proposed recommendations as new findings become available

Serum vitamin D concentration and short-term mortality among geriatric inpatients in acute care settings

Introduction Vitamin D insufficiency is related to acute medical conditions known to increase the risk of short-term death in older adults. The objective of this study was to determine whether serum 25-hydroxyvitamin D (25OHD) concentrations were associated with the occurrence of in-hospital mortality in geriatric acute care settings while taking into account all characteristics likely to improve the rate of in-hospital mortality. Methods Three hundred ninety-nine Caucasian adults admitted between January and October 2009 to the geriatric acute care unit of Angers University Hospital, France were included in this cross-sectional study. The occurrence of all-cause in-hospital death and the measurement of serum 25OHD were assessed. Age, gender, body mass index, supine systolic blood pressure, numbers of acute diseases, chronic diseases, and hospital days, serum albumin, creatinine clearance, and season of hospital admission were used as potential confounders. Results Mean serum 25OHD was 34.88±1.7 nmol/L. Seventeen deaths occurred in the acute care unit. Only serum 25OHD concentration was significantly and independently associated with in-hospital death (adjusted odds ratio [OR] 0.65; 95% CI: 0.44, 0.96; P=0.029 for full adjusted logistic regression. OR 0.87; 95% CI: 0.76, 0.99; P=0.029 fo or step-wise backward model). Conclusion Increased serum 25OHD concentrations were associated with a low in-hospital mortality rate in this cohort of acute care geriatric inpatients. It is not only a new orientation of research,but also an additional argument for prescribing vitamin D in deficient older adults