David J. Llewellyn

Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality—A review of recent evidence

BACKGROUND Optimal vitamin D intake and its status are important not only for bone and calcium-phosphate metabolism, but also for overall health and well-being. Vitamin D deficiency and insufficiency as a global health problem are likely to be a risk for wide spectrum of acute and chronic illnesses. METHODS A review of randomized controlled trials, meta-analyses, and other evidence of vitamin D action on various health outcomes. RESULTS Adequate vitamin D status seems to be protective against musculoskeletal disorders (muscle weakness, falls, fractures), infectious diseases, autoimmune diseases, cardiovascular disease, type 1 and type 2 diabetes mellitus, several types of cancer, neurocognitive dysfunction and mental illness, and other diseases, as well as infertility and adverse pregnancy and birth outcomes. Vitamin D deficiency/insufficiency is associated with all-cause mortality. CONCLUSIONS Adequate vitamin D supplementation and sensible sunlight exposure to reach optimal vitamin D status are among the front line factors of prophylaxis for the spectrum of disorders. Supplementation guidance and population strategies for the eradication of vitamin D deficiency must be included in the priorities of physicians, medical professionals and healthcare policy-makers.

Vitamin D and risk of cognitive decline in elderly persons

BACKGROUND To our knowledge, no prospective study has examined the association between vitamin D and cognitive decline or dementia. METHODS We determined whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with an increased risk of substantial cognitive decline in the InCHIANTI population-based study conducted in Italy between 1998 and 2006 with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE), and substantial decline was defined as 3 or more points. The Trail-Making Tests A and B were also used, and substantial decline was defined as the worst 10% of the distribution of decline or as discontinued testing. RESULTS The multivariate adjusted relative risk (95% confidence interval [CI]) of substantial cognitive decline on the MMSE in participants who were severely serum 25(OH)D deficient (levels <25 nmol/L) in comparison with those with sufficient levels of 25(OH)D (>/=75 nmol/L) was 1.60 (95% CI, 1.19-2.00). Multivariate adjusted random-effects models demonstrated that the scores of participants who were severely 25(OH)D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH)D. The relative risk for substantial decline on Trail-Making Test B was 1.31 (95% CI, 1.03-1.51) among those who were severely 25(OH)D deficient compared with those with sufficient levels of 25(OH)D. No significant association was observed for Trail-Making Test A. CONCLUSION Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention.

Frailty, Body Mass Index, and Abdominal Obesity in Older People

BACKGROUND Frailty has been conceptualized as a wasting disorder with weight loss as a key component. However, obesity is associated with disability and with physiological markers also recently linked with frailty, for example, increased inflammation and low antioxidant capacity. We aimed to explore the relationship between frailty and body mass index (BMI) in older people. METHODS Data were from 3,055 community-dwelling adults aged 65 years and older who participated in the English Longitudinal Study of Ageing. Frailty was defined both by an index of accumulated deficits and by the Fried phenotype. BMI was divided into five categories, and waist circumference 88 cm or more (for women) and 102 cm or more (for men) was defined as high. Analyses were adjusted for sex, age, wealth, level of education, and smoking status. RESULTS The association between BMI and frailty showed a U-shaped curve. This relationship was consistent across different frailty measures. The lowest frailty index (FI) scores and lowest prevalence of Fried frailty were in those with BMI 25-29.9. At each BMI category, and using either measure of frailty, those with a high waist circumference were significantly more frail. CONCLUSIONS Both the phenotypic definition of frailty and the FI show increased levels of frailty among those with low and very high BMIs. In view of the rise in obesity in older populations, the benefits and feasibility of diet and exercise for obese older adults should be a focus of urgent inquiries. The association of frailty with a high waist circumference, even among underweight older people, suggests that truncal obesity may be an additional target for intervention.

Vitamin D, cognition, and dementia A systematic review and meta-analysis

Objective: To examine the association between cognitive function and dementia with vitamin D concentration in adults. Methods: Five databases were searched for English-language studies up to August 2010, and included all study designs with a comparative group. Cognitive function or impairment was defined by tests of global or domain-specific cognitive performance and dementia was diagnosed according to recognized criteria. A vitamin D measurement was required. Two authors independently extracted data and assessed study quality using predefined criteria. The Q statistic and I2 methods were used to test for heterogeneity. We conducted meta-analyses using random effects models for the weighted mean difference (WMD) and Hedges g. Results: Thirty-seven studies were included; 8 contained data allowing mean Mini-Mental State Examination (MMSE) scores to be compared between participants with vitamin D <50 nmol/L to those with values ≥50 nmol/L. There was significant heterogeneity among the studies that compared the WMD for MMSE but an overall positive effect for the higher vitamin D group (1.2, 95% confidence interval [CI] 0.5 to 1.9; I2 = 0.65; p = 0.002). The small positive effect persisted despite several sensitivity analyses. Six studies presented data comparing Alzheimer disease (AD) to controls but 2 utilized a method withdrawn from commercial use. For the remaining 4 studies the AD group had a lower vitamin D concentration compared to the control group (WMD = −6.2 nmol/L, 95% CI −10.6 to −1.8) with no heterogeneity (I2 < 0.01; p = 0.53). Conclusion: These results suggest that lower vitamin D concentrations are associated with poorer cognitive function and a higher risk of AD. Further studies are required to determine the significance and potential public health benefit of this association.

Mediterranean Diet, Cognitive Function, and Dementia A Systematic Review

Background: Adherence to a Mediterranean diet has been associated with lower risk of various age-related diseases including dementia. Although narrative reviews have been published, no systematic review has synthesized studies on the association between Mediterranean diet adherence and cognitive function or dementia. Methods: We conducted a systematic review of 11 electronic databases (including Medline) of published articles up to January 2012. Reference lists, selected journal contents, and relevant websites were also searched. Study selection, data extraction, and quality assessment were performed independently by two reviewers using predefined criteria. Studies were included if they examined the association between a Mediterranean diet adherence score and cognitive function or dementia. Results: Twelve eligible papers (11 observational studies and one randomized controlled trial) were identified, describing seven unique cohorts. Despite methodological heterogeneity and limited statistical power in some studies, there was a reasonably consistent pattern of associations. Higher adherence to Mediterranean diet was associated with better cognitive function, lower rates of cognitive decline, and reduced risk of Alzheimer disease in nine out of 12 studies, whereas results for mild cognitive impairment were inconsistent. Conclusions: Published studies suggest that greater adherence to Mediterranean diet is associated with slower cognitive decline and lower risk of developing Alzheimer disease. Further studies would be useful to clarify the association with mild cognitive impairment and vascular dementia. Long-term randomized controlled trials promoting a Mediterranean diet may help establish whether improved adherence helps to prevent or delay the onset of Alzheimer disease and dementia.

Vitamin D and the risk of dementia and Alzheimer disease

Objective: To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. Methods: One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population–based Cardiovascular Health Study between 1992–1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992–1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimers Disease and Related Disorders Association criteria. Results: During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI: 1.23–4.13) and 1.53 (95% CI: 1.06–2.21) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02–4.83) and 1.69 (95% CI: 1.06–2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L. Conclusion: Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.

Serum 25-Hydroxyvitamin D Concentration and Cognitive Impairment

Vitamin D may be of interest in the prevention of cognitive impairment, though previous findings are inconclusive. Participants were 1766 adults aged 65 years and older from the Health Survey for England 2000, a nationally representative population-based study. Cognitive impairment was assessed using the Abbreviated Mental Test Score. The cross-sectional relation of serum 25-hydroxyvitamin D quartiles to cognitive impairment was modeled using logistic regression. In all, 212 participants (12%) were cognitively impaired. Odds ratios (95% confidence intervals) for cognitive impairment in the first (8-30 nmol/L), second (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), after adjustment for age, sex, education, ethnicity, season of testing, and additional risk factors for cognitive impairment (P for linear trend = .001). Our data suggest low serum 25-hydroxyvitamin D is associated with increased odds of cognitive impairment.

Obesity, physical function, and mortality in older adults

OBJECTIVES: To estimate the effects of excess body weight on objective and subjective physical function and mortality risks in noninstitutionalized older adults.

Prevalence of Neuropsychiatric Symptoms and Their Association with Functional Limitations in Older Adults in the United States: The Aging, Demographics, and Memory Study

OBJECTIVES: To estimate the prevalence of neuropsychiatric symptoms and examine their association with functional limitations.

Neighborhood Deprivation, Individual Socioeconomic Status, and Cognitive Function in Older People: Analyses from the English Longitudinal Study of Ageing

OBJECTIVES: To assess the relationship between cognitive function, socioeconomic status, and neighborhood deprivation (lack of local resources of all types, financial and otherwise).