Bones, brains and B-vitamins : the impact of vitamin B12, folate and homocysteine on bone health and cognitive function in elderly

ABackground An elevated homocysteine level has been indicated as a risk factor for cardiovascular disease, cognitive decline, and fractures. Supplementation of vitamin B12 and folic acid in order to normalize homocysteine levels might be of substantial public health importance as this might reduce the risk for several age-related conditions. This thesis focuses on two health outcomes frequently associated with elevated homocysteine levels and low levels of vitamin B12 and folate: osteoporosis and cognitive decline later in life. Methods Findings are presented in the context of a model which links dietary intake to biomarkers of nutritional status and subsequently to health outcomes. Two systematic reviews with meta-analyses investigated the current status of knowledge about the association of vitamin B12 intake and status with cognitive function, and the association of homocysteine, vitamin B12 and folate status with bone health. Baseline data of the B-PROOF study were used to assess 1) the association of vitamin B12 intake with status according to four biomarkers (vitamin B12, holotranscobalamin (holoTC), methylmalonic acid (MMA) and homocysteine), 2) the mutual association among these four vitamin B12 biomarkers and 3) the association between homocysteine, vitamin B12 biomarkers, folate and cognitive function. The effect of 2-year daily vitamin B12 (500 μg) and folic acid (400 μg) supplementation on fracture risk was assessed in the B-PROOF study, a large (N=2919) randomized controlled trial in elderly people (aged ≥65 years) with an elevated homocysteine level (≥12.0 µmol/L). Results The systematic review of the literature showed no or inconsistent associations of vitamin B12 intake with cognitive function. Furthermore, serum vitamin B12 was not associated with risk of dementia, global cognition or memory. Studies on MMA and holoTC reported significant associations with risk of dementia, Alzheimer’s disease and global cognition. A meta-analysis showed that serum/plasma vitamin B12 per 50 pmol/L was borderline significantly associated with a lower fracture risk (RR=0.96, 95% CI = 0.92-1.00) and that homocysteine was significantly associated with a higher fracture risk (RR=1.04, 95% CI = 1.02-1.07). Meta-analyses regarding vitamin B12, folate and homocysteine levels and BMD did not show significant associations. In the B-PROOF study a doubling of vitamin B12 intake was associated with 9% higher levels of vitamin B12, 15% higher holoTC, 9% lower MMA and 2% lower homocysteine, saturation of biomarkers occurs with dietary intakes of >5 μg B12. Levels of MMA and homocysteine were higher when vitamin B12 levels were below 330 pmol/L and when holoTC levels were below 100 pmol/L, with a steep elevation when levels of vitamin B12 and HoloTC were below 220 and 50 pmol/L respectively. At baseline, levels of vitamin B12 and holoTC were not associated with cognitive function in any cognitive domain. Levels of homocysteine (β= -0.009), folate (β= 0.002), MMA (β= -0.163) and the wellness score – a vitamin B12 biomarker combination score - (β= 0.048) were significantly associated with the domain of episodic memory. Additionally, homocysteine (β= -0.015) and the wellness score (β= 0.103) were significantly associated with the domain information processing speed. The B-PROOF intervention did not lower the risk of fracture in the total population (HR=0.84, 95% CI = 0.58-1.22). Per protocol subgroup analysis of elderly aged >80 years, showed a lower risk of fracture in the intervention group (HR=0.28, 95% CI 0.10-0.74). We observed more cancer cases in the intervention group (HR=1.55, 95% CI = 1.04-2.30) compared to the placebo group. We cannot rule out the possibility of accelerated cancer progression as a possible negative side effect. Conclusion Our literature reviews and observational data confirm an association of levels of homocysteine, vitamin B12 and folate with cognitive function and fracture risk in elderly. Supplementation with vitamin B12 and folic acid did not lower the risk of fracture in the total study population. Though positive effects on fracture incidence emerged in elderly aged >80 years, these benefits should be weighed against potential risks.</p

Complexity in Spanish optical fiber and SDH transport networks

Complex networks are important instances of technology-related complex systems. In this work we apply tools from complexity science to characterise two Telefónica España transport network systems: the optical fiber network and the SDH transport network. We compare both cases and derive its most important properties. Remarkably, our results show that in both cases several features of heterogeneous, hierarchical complex networks arise

A framework for understanding outcomes of integrated care programs for the hospitalised elderly

__Abstract__ __Introduction__: Integrated care has emerged as a new strategy to enhance the quality of care for hospitalised elderly. Current models do not provide insight into the mechanisms underlying integrated care delivery. Therefore, we developed a framework to identify the underlying mechanisms of integrated care delivery. We should understand how they operate and interact, so that integrated care programmes can enhance the quality of care and eventually patient outcomes. Theory and methods: Interprofessional collaboration among professionals is considered to be critical in integrated care delivery due to many interdependent work requirements. A review of integrated care components brings to light a distinction between the cognitive and behavioural components of interprofessional collaboration. __Results__: Effective integrated care programmes combine the interactin

Understanding implementation of comprehensive geriatric care programs: a multiple perspective approach is preferred

Background: The Prevention and Reactivation Care Program (PReCaP) provides a novel approach targeting hospital-related functional decline among elderly patients. Despite the high expectations, the PReCaP was not effective in preventing functional decline (ADL and iADL) among older patients. Although elderly PReCaP patients demonstrated slightly better cognitive functioning (Mini Mental State Examination; 0.4 [95% confidence interval (CI) 0.2–0.6]), lower depression (Geriatric Depression Scale 15; –0.9 [95% –1.1 to –0.6]), and higher perceived health (Short-form 20; 5.6 [95% CI 2.8–8.4]) 1 year after admission than control patients, the clinical relevance was limited. Therefore, this study aims to identify factors impacting on the effectiveness of the implementation of the PReCaPand geriatric care ‘as usual’. Methods: We conducted semi-structured interviews with 34 professionals working with elderly patients in three hospitals, selected for their comparable patient case mix and different levels of geriatric care. Five non-participatory observations were undertaken during multidisciplinary meetings. Patient files (n = 42), hospital protocols, and care plans were screened for elements of geriatric care. Clinical process data were analysed for PReCaP components. Results: The establishment of a geriatric unit and employment of geriatricians demonstrates commitment to geriatric care in hospital A. Although admission processes are comparable, early identification of frail elderly patients only takes place in hosptial A. Furthermore, nursing care in the hospital A geriatric unit excels with regard to maximizing patient independency, an important predictor for hospital-related functional decline. Transfer nurses play a key role in arranging post-discharge geriatric follow-up care. Geriatric consultations are performed by g

The Prevention and Reactivation Care Program: intervention fidelity matters.

The Prevention and Reactivation Care Program (PReCaP) entails an innovative multidisciplinary, integrated and goal oriented approach aimed at reducing hospital related functional decline among elderly patients. Despite calls for process evaluation as an essential component of clinical trials in the geriatric care field, studies assessing fidelity lag behind the number of effect studies. The threefold purpose of this study was (1) to systematically assess intervention fidelity of the hospital phase of the PReCaP in the first year of the intervention delivery; (2) to improve our understanding of the moderating factors and modifications affecting intervention fidelity; and (3) to explore the feasibility of the PReCaP fidelity assessment in view of the modifications. Based on the PReCaP description we developed a fidelity instrument incorporating nineteen (n=19) intervention components. A combination of data collection methods was utilized, i.e. data collection from patient records and individual Goal Attainment Scaling care plans, in-depth interviews with stakeholders, and non-participant observations. Descriptive analysis was performed to obtain levels of fidelity of each of the nineteen PReCaP components. Moderating factors were identified by using the Conceptual Framework for Implementation Fidelity. Ten of the nineteen intervention components were always or often delivered to the group of twenty elderly patients. Moderating factors, suc

Dietary sources of vitamin B-12 and their association with vitamin B-12 status markers in healthy older adults in the B-PROOF study

Low vitamin B-12 concentrations are frequently observed among older adults. Malabsorption is hypothesized to be an important cause of vitamin B-12 inadequacy, but serum vitamin B-12 may also be differently affected by vitamin B-12 intake depending on food source. We examined associations between dietary sources of vitamin B-12 (meat, fish and shellfish, eggs, dairy) and serum vitamin B-12, using cross-sectional data of 600 Dutch community-dwelling adults (≥65 years). Dietary intake was assessed with a validated food frequency questionnaire. Vitamin B-12 concentrations were measured in serum. Associations were studied over tertiles of vitamin B-12 intake using P for trend, by calculating prevalence ratios (PRs), and splines. Whereas men had significantly higher vitamin B-12 intakes than women (median (25th–75th percentile): 4.18 (3.29–5.38) versus 3.47 (2.64–4.40) µg/day), serum vitamin B-12 did not differ between the two sexes (mean ± standard deviation (SD): 275 ± 104 pmol/L versus 290 ± 113 pmol/L). Higher intakes of dairy, meat, and fish and shellfish were significantly associated with higher serum vitamin B-12 concentrations, where meat and dairy—predominantly milk were the most potent sources. Egg intake did not significantly contribute to higher serum vitamin B-12 concentrations. Thus, dairy and meat were the most important contributors to serum vitamin B-12, followed by fish and shellfish

A Randomized Controlled Trial to Examine the Effect of 2-Year Vitamin B12 and Folic Acid Supplementation on Physical Performance, Strength, and Falling: Additional Findings from the B-PROOF Study

Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged ≥65 years with elevated plasma homocysteine concentrations [12–50 µmol/L (n = 2919)] were randomly assigned to daily supplementation of 500 µg vitamin B12, 400 µg folic acid, and 600 I

Low vitamin D status is associated with more depressive symptoms in Dutch older adults

Purpose: The existence of vitamin D receptors in the brain points to a possible role of vitamin D in brain function. We examined the association of vitamin D status and vitamin D-related genetic make-up with depressive symptoms amongst 2839 Dutch older adults aged ≥65 years. Methods: 25-Hydroxyvitamin D (25(OH)D) was measured, and five ‘vitamin D-related genes’ were selected. Depressive symptoms were measured with the 15-point Geriatric Depression Scale. Results were expressed as the relative risk of the score of depressive symptoms by quartiles of 25(OH)D concentration or number of affected alleles, using the lowest quartile or minor allele group as reference. Results: A clear cross-sectional and pr

The first titin (c.59926+1G > A) founder mutation associated with dilated cardiomyopathy

Cardiolog

Effect of Vitamin B<inf>12</inf> and Folic Acid Supplementation on Bone Mineral Density and Quantitative Ultrasound Parameters in Older People with an Elevated Plasma Homocysteine Level: B-PROOF, a Randomized Controlled Trial

High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged ≥65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p 80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement