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Aim: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B 12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B 12 supplementation with participants who did not., Methods: Participants of the B-PROOF study ( n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B 12 , or a placebo. After two years of intervention, T₁-weighted magnetic resonance imaging (MRI) scans were made in a random subsample ( n = 218) to obtain grey and white matter volume, and total brain volume (TBV). Plasma homocysteine, serum folate, vitamin B 12 , holotranscobalamin, and methylmalonic acid concentrations were measured., Results: Multiple linear regression analyses showed inverse associations between plasma homocysteine with TBV (β = -0.91, 95% CI -1.85-0.03; p = 0.06) and between serum folate and TBV (β = -0.20, 95% CI -0.38, -0.02; p = 0.03). No significant associations were observed for serum vitamin B 12 and holotranscobalamin. Fully adjusted ANCOVA models showed that the group that received B-vitamins had a lower TBV (adjusted mean 1064, 95% CI 1058-1069 mL) than the non-supplemented group (1072, 95% CI 1067-1078 mL, p = 0.03)., Conclusions: Results were contradictory, with higher Hcy levels associated with lower TBV, but also with higher folate levels associated with lower TBV. In addition, the lack of a baseline measurement withholds us from giving recommendations on whether folic acid and vitamin B 12 supplementation will be beneficial above and beyond normal dietary intake for brain health., Competing Interests: The authors declare no conflict of interest.

Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing vitamin B 12 and folic acid may reduce depressive symptoms and improve health-related quality of life (HR-QoL) in older adults. This study aimed to test this hypothesis in a randomized controlled trial. Participants ( N = 2919, ≥65 years, Hcy concentrations ≥12 µmol/L) received either 500 µg vitamin B 12 and 400 µg folic acid daily or placebo for two years. Both tablets contained 15 µg vitamin D₃. Depressive symptoms were measured with the Geriatric Depression Scale-15 (GDS-15). HR-QoL was assessed with the SF-12 Mental and Physical component summary scores and the EQ-5D Index score and Visual Analogue Scale. Differences in two-year change scores were analyzed with Analysis of Covariance (ANCOVA). Hcy concentrations decreased more in the intervention group, but two-year change scores of the GDS-15 and three of four HR-QoL measures did not differ between groups. The EQ-5D Index score declined less in the intervention group than in the placebo group (mean change 0.00 vs. -0.02, p = 0.004). In conclusion, two-year supplementation with vitamin B 12 and folic acid in older adults with hyperhomocysteinemia showed that lowering Hcy concentrations does not reduce depressive symptoms, but it may have a small positive effect on HR-QoL., Competing Interests: The authors declare no conflict of interest. The funding sources had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Background/objectives: The prevalence of vitamin D deficiency among seniors is high. Whereas sun exposure, vitamin D intake, genes, demographics, and lifestyle have been identified as being important determinants of vitamin D status, the impact of these factors is expected to differ across populations. To improve current prevention and treatment strategies, this study aimed to explore the main determinants of vitamin D status and its relative importance in a population of community-dwelling Dutch older adults., Methods/subjects: Serum 25-hydroxyvitamin D (25(OH)D) was measured in 2857 adults aged ≥65 years. Sun exposure was assessed with a structured questionnaire (n=1012), vitamin D intake using a Food Frequency Questionnaire (n=596), and data on genetic variation that may affect 25(OH)D status was obtained for 4 genes, DHCR7 (rs12785878), CYP2R1 (rs10741657), GC (rs2282679), and CYP24A1 (rs6013897) (n=2530)., Results: Serum 25(OH)D concentrations <50nmol/L were observed in 45% of the population; only 6% of these participants used vitamin D supplements. Sun exposure (being outside daily during summer: 66±25nmol/L vs not being outside daily during summer: 58±27nmol/L, P=0.02) and vitamin D intake (per unit μg/day during winter/spring: 3.1±0.75nmol/L, P<0.0001) were associated with higher 25(OH)D concentrations. Major allele carriers of SNPs related to DHCR7, CYP24A1, and GC, as well as CYP2R1 minor allele carriers had the highest 25(OH)D concentrations. Together, sun (R 2 =0.29), vitamin D intake (R 2 =0.24), and genes (R 2 =0.28) explained 35% (R 2 =0.35) of the variation in 25(OH)D concentrations during summer/autumn period, when adjusted for age, sex, BMI, education, alcohol consumption, smoking, physical activity, and self-rated health status (n=185)., Conclusion: The investigated determinants explained 35% of 25(OH)D status. Of the three main determinants under study, sun exposure still appeared to be an important determinant of serum 25(OH)D in older individuals, closely followed by genes, and vitamin D intake. Given the low frequency of vitamin D supplement use in this population, promoting supplement use may be an inexpensive, easy, and effective strategy to fight vitamin D deficiency., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Undernutrition risk among community-dwelling older adults is partly caused by inadequate protein intake. Enriching readymade meals with protein could be beneficial in increasing protein intake. Moreover, reduced-size meals could suit older adults with diminished appetite. In this single-blind randomized crossover study with 120 participants (age: 70.5 ± 4.5 y, BMI: 27.2 ± 4.4 kg/m(2)), 60 participants consumed four beef meals and another 60 consumed four chicken meals on four different days, once per week. These meals were produced according to a 2 × 2 factorial design: the protein content was either ∼25 g (lower) or ∼30 g (enriched), and the portion size was either 450 g (normal) or of 400 g (reduced). Palatability evaluation, meal intake, and subsequent satiety ratings after 120 min were measured. No significant differences in palatability among meals were found. While absolute intake (g) of the normal-size meals was significantly higher than that of the reduced-size meals, the relative intake (%) of the served meals did not differ between the four meals. Both protein and energy intakes were significantly higher for the enriched meals, regardless of portion size. Protein intakes were 5.4 g and 5.1 g higher in the normal-size and reduced-size enriched beef meals, respectively, and 6.1 g and 7.1 g higher in the enriched chicken meals, respectively. The normal-size enriched beef meal and reduced-size enriched chicken meal led to slightly but significantly higher ratings of satiety than the non-enriched meals. Due to these mixed satiety findings, separate effects of meal-size reduction and protein enrichment could not be distinguished in this study. The intake findings show that palatable protein-enriched meals support higher protein and energy intakes in vital community-dwelling older adults during a single meal., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

With aging, energy needs decrease, necessitating a more nutrient-dense diet to meet nutritional needs. To bridge this gap, the use of nutrient-dense foods, fortified foods, and dietary supplements can be important. This observational study aims to describe current micronutrient intakes of Dutch elderly and to identify the contribution of nutrient-dense foods, fortified foods, and dietary supplements to the intake of micronutrients that are often inadequately consumed in Dutch elderly. Data of 245 Dutch volunteers from the NU-AGE study aged 65 to 80 years were used. Dietary intake was assessed by means of 7-day food records, and dietary supplement use was recorded with an additional questionnaire. Information on fortified foods was obtained from the Dutch Food Composition Table 2011. Nutrient density of foods was evaluated using the Nutrient Rich Food 9.3 score. The percentages of participants not meeting their average requirement were high for vitamin D (99%), selenium (41%), and vitamin B6 (54%) based on conventional foods and also when taking into account fortified foods (98%, 41%, and 27%, respectively) and vitamin and mineral supplements (87%, 36%, and 20%, respectively). Conventional foods were the main source of vitamin D, vitamin B6, and selenium intake (42%, 45%, and 82%, respectively), followed by vitamin and mineral supplements (41%, 44%, and 18%) and fortified foods (17%, 11%, and 1%). Foods with the highest nutrient density contributed most to total vitamin B6 intake only. To optimize nutrient intakes of elderly, combinations of natural food sources, fortified foods, and dietary supplements should be considered., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

[This corrects the article DOI: 10.1371/journal.pgen.1005378.].

Background: There is growing evidence of a relationship between nutrients and muscle mass, strength, and physical performance. Although nutrition is seen as an important pillar of treating sarcopenia, data on the nutritional intake of sarcopenic older adults are limited., Objective: To investigate potential nutritional gaps in the sarcopenic population, the present study compared nutrient intake and biochemical nutrient status between sarcopenic and nonsarcopenic older adults., Design: The Maastricht Sarcopenia Study included 227 community-dwelling older adults (≥65 years) from Maastricht, 53 of whom were sarcopenic based on the European Working Group on Sarcopenia in Older People algorithm. Habitual dietary intake was assessed with a food frequency questionnaire and data on dietary supplement use were collected. In addition, serum 25-hydroxyvitamin D, magnesium and α-tocopherol/cholesterol, plasma homocysteine and red blood cell n-3, and n-6 fatty acids profiles were assessed. Nutrient intake and biochemical nutrient status of the sarcopenic groups were compared with those of the nonsarcopenic groups. The robustness of these results was tested with a multiple regression analysis, taking into account between-group differences in characteristics., Results: Sarcopenic older adults had a 10%-18% lower intake of 5 nutrients (n-3 fatty acids, vitamin B6, folic acid, vitamin E, magnesium) compared with nonsarcopenic older adults (P < .05). When taking into account dietary supplement intake, a 19% difference remained for n-3 fatty acids intake (P = .005). For the 2 biochemical status markers, linoleic acid and homocysteine, a 7% and 27% difference was observed, respectively (P < .05). The higher homocysteine level confirmed the observed lower vitamin B intake in the sarcopenic group. Observed differences in eicosapentaenoic acid and 25-hydroxyvitamin D between the groups were related to differences in age and living situation., Conclusions: Sarcopenic older adults differed in certain nutritional intakes and biochemical nutrient status compared with nonsarcopenic older adults. Dietary supplement intake reduced the gap for some of these nutrients. Targeted nutritional intervention may therefore improve the nutritional intake and biochemical status of sarcopenic older adults., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

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 IU vitamin D3, or to placebo with 600 IU vitamin D3. Physical performance (range 0-12) and handgrip strength (kg) were measured at baseline and after 2 years. Falls were reported prospectively on a research calendar. Intention-to-treat (primary) and per-protocol (secondary) analyses were performed. Physical performance level and handgrip strength significantly decreased during the follow-up period, but this decline did not differ between groups. Moreover, time to first fall was not significantly different (HR: 1.0, 95% CI 0.9-1.2). Secondary analyses on a per-protocol base identified an interaction effect with age on physical performance. In addition, the treatment was associated with higher follow-up scores on the walking test (cumulative OR: 1.3, 95% CI 1.1-1.5). Two-year supplementation of vitamin B12 and folic acid was neither effective in reducing the age-related decline in physical performance and handgrip strength, nor in the prevention of falling in elderly persons. Despite the overall null-effect, the results provide indications for a positive effect of the intervention on gait, as well as on physical performance among compliant persons >80 years. These effects should be further tested in future studies.

Introduction: Sufficient high quality dietary protein intake is required to prevent or treat sarcopenia in elderly people. Therefore, the intake of specific protein sources as well as their timing of intake are important to improve dietary protein intake in elderly people., Objectives: to assess the consumption of protein sources as well as the distribution of protein sources over the day in community-dwelling, frail and institutionalized elderly people., Methods: Habitual dietary intake was evaluated using 2- and 3-day food records collected from various studies involving 739 community-dwelling, 321 frail and 219 institutionalized elderly people., Results: Daily protein intake averaged 71 ± 18 g/day in community-dwelling, 71 ± 20 g/day in frail and 58 ± 16 g/day in institutionalized elderly people and accounted for 16% ± 3%, 16% ± 3% and 17% ± 3% of their energy intake, respectively. Dietary protein intake ranged from 10 to 12 g at breakfast, 15 to 23 g at lunch and 24 to 31 g at dinner contributing together over 80% of daily protein intake. The majority of dietary protein consumed originated from animal sources (≥60%) with meat and dairy as dominant sources. Thus, 40% of the protein intake in community-dwelling, 37% in frail and 29% in institutionalized elderly originated from plant based protein sources with bread as the principle source. Plant based proteins contributed for >50% of protein intake at breakfast and between 34% and 37% at lunch, with bread as the main source. During dinner, >70% of the protein intake originated from animal protein, with meat as the dominant source., Conclusion: Daily protein intake in these older populations is mainly (>80%) provided by the three main meals, with most protein consumed during dinner. More than 60% of daily protein intake consumed is of animal origin, with plant based protein sources representing nearly 40% of total protein consumed. During dinner, >70% of the protein intake originated from animal protein, while during breakfast and lunch a large proportion of protein is derived from plant based protein sources.

Introduction: Smoking is known to be a major cause of death among middle-aged adults, but evidence on its impact and the benefits of smoking cessation among older adults has remained limited. Therefore, we aimed to estimate the influence of smoking and smoking cessation on all-cause mortality in people aged ≥60 years., Methods: Relative mortality and mortality rate advancement periods (RAPs) were estimated by Cox proportional hazards models for the population-based prospective cohort studies from Europe and the U.S. (CHANCES [Consortium on Health and Ageing: Network of Cohorts in Europe and the U.S.]), and subsequently pooled by individual participant meta-analysis. Statistical analyses were performed from June 2013 to March 2014., Results: A total of 489,056 participants aged ≥60 years at baseline from 22 population-based cohort studies were included. Overall, 99,298 deaths were recorded. Current smokers had 2-fold and former smokers had 1.3-fold increased mortality compared with never smokers. These increases in mortality translated to RAPs of 6.4 (95% CI=4.8, 7.9) and 2.4 (95% CI=1.5, 3.4) years, respectively. A clear positive dose-response relationship was observed between number of currently smoked cigarettes and mortality. For former smokers, excess mortality and RAPs decreased with time since cessation, with RAPs of 3.9 (95% CI=3.0, 4.7), 2.7 (95% CI=1.8, 3.6), and 0.7 (95% CI=0.2, 1.1) for those who had quit <10, 10 to 19, and ≥20 years ago, respectively., Conclusions: Smoking remains as a strong risk factor for premature mortality in older individuals and cessation remains beneficial even at advanced ages. Efforts to support smoking abstinence at all ages should be a public health priority., (Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

Objectives: First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance., Design, Setting, and Participants: Associations were studied using cross-sectional data of 776 (3 domains) up to 2722 (1 domain) Dutch community-dwelling older adults, aged 65 years or older., Measurements: Serum 25(OH)D, plasma glucose, and insulin concentrations were obtained. Cognitive performance was assessed with an extensive cognitive test battery. Prevalence ratios (PRs) were calculated to quantify the association between 25(OH)D and cognition; poor performance was defined as the worst 10% of the distribution of the cognitive scores., Results: The overall median MMSE score was 29 (IQR 28-30). Higher serum 25(OH)D was associated with better attention and working memory, PR 0.50 (95% CI 0.29-0.84) for the third serum 25(OH)D tertile, indicating a 50% lower probability of being a poor performer than participants in the lowest tertile. Beneficial trends were shown for 25(OH)D with executive function and episodic memory. Serum 25(OH)D was not associated with plasma glucose or insulin. Plasma insulin only modified the association between serum 25(OH)D and executive function (P for interaction: .001), suggesting that the improvement in executive function with high 25(OH)D concentrations is stronger in participants with high plasma insulin concentrations compared with those with low plasma insulin concentrations., Conclusion: Higher 25(OH)D concentrations significantly associated with better attention and working memory performance. This study does not demonstrate an interplay between serum 25(OH)D and glucose homeostasis in the association with cognitive performance., (Copyright © 2015 AMDA - The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the proposed prevalence of unresponsiveness of older men and women to augment lean body mass, muscle fiber size, muscle strength, and/or physical function following prolonged resistance-type exercise training., Design/setting/participants: A retrospective analysis of the adaptive response to 12 (n = 110) and 24 (n = 85) weeks of supervised resistance-type exercise training in older (>65 years) men and women., Measurements: Lean body mass (DXA), type I and type II muscle fiber size (biopsy), leg strength (1-RM on leg press and leg extension), and physical function (chair-rise time) were assessed at baseline, and after 12 and 24 weeks of resistance-type exercise training., Results: Lean body mass increased by 0.9 ± 0.1 kg (range: -3.3 to +5.4 kg; P < .001) from 0 to 12 weeks of training. From 0 to 24 weeks, lean body mass increased by 1.1 ± 0.2 kg (range: -1.8 to +9.2 kg; P < .001). Type I and II muscle fiber size increased by 324 ± 137 μm(2) (range: -4458 to +3386 μm(2); P = .021), and 701 ± 137 μm(2) (range: -4041 to +3904 μm(2); P < .001) from 0 to 12 weeks. From 0 to 24 weeks, type I and II muscle fiber size increased by 360 ± 157 μm(2) (range: -3531 to +3426 μm(2); P = .026) and 779 ± 161 μm(2) (range: -2728 to +3815 μm(2); P < .001). The 1-RM strength on the leg press and leg extension increased by 33 ± 2 kg (range: -36 to +87 kg; P < .001) and 20 ± 1 kg (range: -22 to +56 kg; P < .001) from 0 to 12 weeks. From 0 to 24 weeks, leg press and leg extension 1-RM increased by 50 ± 3 kg (range: -28 to +145 kg; P < .001) and 29 ± 2 kg (range: -19 to +60 kg; P < .001). Chair-rise time decreased by 1.3 ± 0.4 seconds (range: +21.6 to -12.5 seconds; P = .003) from 0 to 12 weeks. From 0 to 24 weeks, chair-rise time decreased by 2.3 ± 0.4 seconds (range: +10.5 to -23.0 seconds; P < .001). Nonresponsiveness was not apparent in any subject, as a positive adaptive response on at least one training outcome was apparent in every subject., Conclusions: A large heterogeneity was apparent in the adaptive response to prolonged resistance-type exercise training when changes in lean body mass, muscle fiber size, strength, and physical function were assessed in older men and women. The level of responsiveness was strongly affected by the duration of the exercise intervention, with more positive responses following more prolonged exercise training. We conclude that there are no nonresponders to the benefits of resistance-type exercise training on lean body mass, fiber size, strength, or function in the older population. Consequently, resistance-type exercise should be promoted without restriction to support healthy aging in the older population., (Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Micronutrient deficiencies and low dietary intakes among community-dwelling older adults are associated with functional decline, frailty and difficulties with independent living. As such, studies that seek to understand the types and magnitude of potential dietary inadequacies might be beneficial for guiding future interventions. We carried out a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Observational cohort and longitudinal studies presenting the habitual dietary intakes of older adults (≥65 years) were included. Sex-specific mean (and standard deviation) habitual micronutrient intakes were extracted from each article to calculate the percentage of older people who were at risk for inadequate micronutrient intakes using the estimated average requirement (EAR) cut-point method. The percentage at risk for inadequate micronutrient intakes from habitual dietary intakes was calculated for twenty micronutrients. A total of thirty-seven articles were included in the pooled systematic analysis. Of the twenty nutrients analysed, six were considered a possible public health concern: vitamin D, thiamin, riboflavin, Ca, Mg and Se. The extent to which these apparent inadequacies are relevant depends on dynamic factors, including absorption and utilisation, vitamin and mineral supplement use, dietary assessment methods and the selection of the reference value. In light of these considerations, the present review provides insight into the type and magnitude of vitamin and mineral inadequacies.

Introduction: Although handgrip strength is considered a strong predictor of negative health outcomes, it is unclear whether handgrip strength represents a useful measure to evaluate changes in muscle strength following resistance-type exercise training in older people. We assessed whether measuring handgrip strength provides proper insight in the efficacy of resistance-type exercise training to increase muscle mass, strength, and physical performance in frail older people., Methods: Prefrail and frail older people (≥ 65 y) were either conducting a 24-week resistance-type exercise training or no exercise training. Before, during, and after the intervention, handgrip strength (JAMAR), lean body mass (DXA), leg strength (1-RM), and physical performance (SPPB) were assessed., Results: Handgrip strength correlated with appendicular lean mass (r = 0.68; p < .001) and leg strength (r = 0.67; p < .001). After 24 weeks of whole body resistance-type exercise training, leg extension strength improved significantly better when compared with the control group (57 ± 2-78 ± 3 kg vs 57 ± 3-65 ± 3 kg: p < .001). Moreover, physical performance improved significantly more in the exercise group (8.0 ± 0.4-9.3 ± 0.4 points) when compared with the control group (8.3 ± 0.4-8.9 ± 0.4 points: p < .05). These positive changes were not accompanied with any significant changes in handgrip strength (26.3 ± 1.2-27.6 ± 1.2 kg in the exercise group vs 26.6 ± 1.2-26.3 ± 1.3 kg in the control group: p = .71)., Conclusion: Although handgrip strength strongly correlates with muscle mass and leg strength in frail older people, handgrip strength does not provide a valid means to evaluate the efficacy of exercise intervention programs to increase muscle mass or strength in an older population.

Glucose is the main fuel for the brain, and manipulation of the glucose supply may consequently affect brain function. The present review was conducted to provide an overview of studies that investigated the acute effects of glucose load on memory and other cognitive functions in elderly people. The effects of sucrose on cognition and suggested mechanisms were also explored. A total of twenty studies met the inclusion criteria. In the majority of studies, episodic memory was investigated and a beneficial role for glucose in that specific cognitive domain was suggested. Other cognitive domains, i.e., working memory, semantic memory, visual memory, information-processing speed, attention, executive function, and visual/spatial function, have been studied less frequently and evidence for a beneficial effect of glucose was equivocal. Mechanisms are suggested to be mainly related to the human body's need for glucose as a metabolic substrate for physiological mechanisms in both central and peripheral processes., (© The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: several studies have been pointing towards a non-linear relationship between serum 25(OH)D and cardiovascular disease. Next to vitamin D deficiency, also higher levels of 25(OH)D have been reported to be associated with increased cardiovascular risk. We aimed to investigate the nature of the relationship between serum 25(OH)D and measures of arterial stiffness and arteriosclerosis in an elderly population., Design: cross-sectional., Setting/subjects: a subgroup of the B-PROOF study was included to determine associations between serum 25(OH)D and arterial stiffness and atherosclerosis (n = 567, 57% male, age 72.6 ± 5.6 years, mean serum 25(OH)D 54.6 ± 24.1 nmol/l)., Methods: carotid intima media thickness (IMT) was assessed using ultrasonography and pulse wave velocity (PWV) was determined with applanation tonometry. Associations were tested using multivariable restricted cubic spline functions and stratified linear regression analysis., Results: the associations between serum 25(OH)D and carotid IMT or PWV were non-linear. Spline functions demonstrated a difference between 25(OH)D deficient and sufficient individuals. In serum 25(OH)D sufficient participants (≥50 nmol/l; n = 287), a positive association with IMT and serum 25(OH)D was present (β 1.24; 95%CI [0.002; 2.473]). PWV levels were slightly lower in vitamin D deficient individuals, but the association with 25(OH)D was not significant., Conclusion: our study demonstrates that associations of serum 25(OH)D and PWV and IMT in an elderly population are not linear. In particular from serum 25(OH)D levels of 50 nmol/l and up, there is a slight increase of IMT with increasing 25(OH)D levels., (© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose of Review: Ageing is a generally known risk factor for cognitive decline and dementia. Underlying mechanisms are expected to be multifactorial, but the exact causes are still elusive. This article reviews the potential role of vitamin D in brain function by presenting an overview of recently published mechanistic, rodent as well as human studies., Recent Findings: There is emerging evidence that suggests a beneficial role for vitamin D in brain physiology, for instance by the promotion of neurotransmission, neurogenesis, synaptogenesis, amyloid clearance and the prevention of neuronal death. In addition, several observational studies have shown associations between higher serum vitamin D concentrations and better cognitive performance. To date, imaging studies and randomized controlled trials are scarce, but these studies are expected to fulfil a crucial role towards a better understanding on vitamin D-mediated brain processes in the future., Summary: Despite accumulating evidence supporting a role of vitamin D in brain function, only a handful of human trials have been performed. Consequently, the question whether the association between vitamin D, cognitive decline and dementia is causal cannot be sufficiently answered yet.

Background: Anorexia of ageing may predispose older adults to under-nutrition and protein energy malnutrition. Studies, however, report a large variation in nutrient inadequacies among community-dwelling older adults., Summary: This systematic review provides a comprehensive overview of the energy and macronutrient intakes and possible inadequacies in community-dwelling older adults. PubMed and EMBASE were screened up to December 2013; data from national nutrition surveys were added. Forty-six studies were included, following the PRISMA guideline., Key Messages: Mean daily energy intake was 8.9 MJ in men and 7.3 MJ in women. Mean daily carbohydrate and protein intakes were 46 and 15 En% in men and 47 and 16 En% in women, respectively. Mean daily total fat, saturated fatty acid (SFA), mono-unsaturated fatty acid (MUFA) and poly-unsaturated fatty acid intakes were respectively 34, 13, 13 and 5-6 En%. The carbohydrates and MUFA intakes are below the acceptable macronutrient distribution ranges (AMDR). Fat intake is relatively high, and SFA intake exceeds the upper-AMDR. Based on the estimated average requirement (EAR) cut-point method, 10-12% of older adults do not meet the EAR for protein. To interpret a possible energy imbalance additional information is needed on physical activity, energy expenditure and body weight changes. This systematic review indicates a suboptimal dietary macronutrient distribution and a large variation in nutrient intakes among community-dwelling older adults., (2015 The Author(s) Published by S. Karger AG, Basel.)

Objective: We investigated the effects of 2-year folic acid and vitamin B12 supplementation on cognitive performance in elderly people with elevated homocysteine (Hcy) levels., Methods: This multicenter, double-blind, randomized, placebo-controlled trial included 2,919 elderly participants (65 years and older) with Hcy levels between 12 and 50 µmol/L. Participants received daily either a tablet with 400 µg folic acid and 500 µg vitamin B12 (B-vitamin group) or a placebo tablet. Both tablets contained 15 µg vitamin D3. Data were available for global cognitive functioning assessed by Mini-Mental State Examination (n = 2,556), episodic memory (n = 2,467), attention and working memory (n = 759), information processing speed (n = 731), and executive function (n = 721)., Results: Mean age was 74.1 (SD 6.5) years. Hcy concentrations decreased 5.0 (95% confidence interval -5.3 to -4.7) µmol/L in the B-vitamin group and 1.3 (-1.6 to -0.9) µmol/L in the placebo group. Cognitive domain scores did not differ over time between the 2 groups, as determined by analysis of covariance. Mini-Mental State Examination score decreased with 0.1 (-0.2 to 0.0) in the B-vitamin group and 0.3 (-0.4 to -0.2) in the placebo group (p = 0.05), as determined by an independent t test., Conclusions: Two-year folic acid and vitamin B12 supplementation did not beneficially affect performance on 4 cognitive domains in elderly people with elevated Hcy levels. It may slightly slow the rate of decline of global cognition, but the reported small difference may be attributable to chance., Classification of Evidence: This study provides Class I evidence that 2-year supplementation with folic acid and vitamin B12 in hyperhomocysteinemic elderly people does not affect cognitive performance., (© 2014 American Academy of Neurology.)

Background: Medication use is a potentially modifiable risk factor for falling; psychotropic and cardiovascular drugs have been indicated as main drug groups that increase fall risk. However, evidence is mainly based on studies that recorded falls retrospectively and/or did not determine medication use at the time of the fall. Therefore, we investigated the associations indicated in the literature between medication use and falls, using prospectively recorded falls and medication use determined at the time of the fall., Methods: Data from the B-PROOF (B-vitamins for the prevention of osteoporotic fractures) study were used, concerning community-dwelling elderly aged ≥65 years. We included 2,407 participants with pharmacy dispensing records. During the 2- to 3-year follow-up, participants recorded falls using a fall calendar. Cox proportional hazard models were applied, adjusting for potential confounders including age, sex, health status variables and concomitant medication use., Results: During follow-up, 1,147 participants experienced at least one fall. Users of anti-arrhythmic medication had an increased fall risk (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.12-2.32) compared with non-users. Similarly, non-selective beta-blocker use was associated with an increased fall risk (HR 1.41 [95% CI 1.12-1.78]), while statin use was associated with a lower risk (HR 0.81 [95% CI 0.71-0.94]). Benzodiazepine use (HR 1.32 [95% CI 1.02-1.71]), and antidepressant use (HR 1.40 [95% CI 1.07-1.82]) were associated with an increased fall risk. Use of other cardiovascular and psychotropic medication was not associated with fall risk., Conclusion: Our results strengthen the evidence for an increased fall risk in community-dwelling elderly during the use of anti-arrhythmics, non-selective beta-blockers, benzodiazepines, and antidepressant medication. Clinicians should prescribe these drugs cautiously and if possible choose safer alternatives for older patients.

Background: Elevated plasma homocysteine concentrations are a risk factor for osteoporotic fractures. Lowering homocysteine with combined vitamin B-12 and folic acid supplementation may reduce fracture risk., Objective: This study [B-vitamins for the PRevention Of Osteoporotic Fractures (B-PROOF)] aimed to determine whether vitamin B-12 and folic acid supplementation reduces osteoporotic fracture incidence in hyperhomocysteinemic elderly individuals., Design: This was a double-blind, randomized, placebo-controlled trial in 2919 participants aged ≥65 y with elevated homocysteine concentrations (12-50 μmol/L). Participants were assigned to receive daily 500 μg vitamin B-12 plus 400 μg folic acid or placebo supplementation for 2 y. Both intervention and placebo tablets also contained 600 IU vitamin D3. The primary endpoint was time to first osteoporotic fracture. Exploratory prespecified subgroup analyses were performed in men and women and in individuals younger than and older than age 80 y. Data were analyzed according to intention-to-treat and per-protocol principles., Results: Osteoporotic fractures occurred in 61 persons (4.2%) in the intervention group and 75 persons (5.1%) in the placebo group. Osteoporotic fracture risk was not significantly different between groups in the intention-to-treat analyses (HR: 0.84; 95% CI: 0.58, 1.21) or per-protocol analyses (HR: 0.81; 95% CI: 0.54, 1.21). For persons aged >80 y, in per-protocol analyses, osteoporotic fracture risk was lower in the intervention group than in the placebo group (HR: 0.27; 95% CI: 0.10, 0.74). The total number of adverse events (including mortality) did not differ between groups. However, 63 and 42 participants in the intervention and placebo groups, respectively, reported incident cancer (HR: 1.56; 95% CI: 1.04, 2.31)., Conclusions: These data show that combined vitamin B-12 and folic acid supplementation had no effect on osteoporotic fracture incidence in this elderly population. Exploratory subgroup analyses suggest a beneficial effect on osteoporotic fracture prevention in compliant persons aged >80 y. However, treatment was also associated with increased incidence of cancer, although the study was not designed for assessing cancer outcomes. Therefore, vitamin B-12 plus folic acid supplementation cannot be recommended at present for fracture prevention in elderly people. The B-PROOF study was registered with the Netherlands Trial Register (trialregister.nl) as NTR1333 and at clinicaltrials.gov as NCT00696414., (© 2014 American Society for Nutrition.)

The World Health Organization (WHO) has formulated guidelines for a healthy diet to prevent chronic diseases and postpone death worldwide. Our objective was to investigate the association between the WHO guidelines, measured using the Healthy Diet Indicator (HDI), and all-cause mortality in elderly men and women from Europe and the United States. We analyzed data from 396,391 participants (42% women) in 11 prospective cohort studies who were 60 years of age or older at enrollment (in 1988-2005). HDI scores were based on 6 nutrients and 1 food group and ranged from 0 (least healthy diet) to 70 (healthiest diet). Adjusted cohort-specific hazard ratios were derived by using Cox proportional hazards regression and subsequently pooled using random-effects meta-analysis. During 4,497,957 person-years of follow-up, 84,978 deaths occurred. Median HDI scores ranged from 40 to 54 points across cohorts. For a 10-point increase in HDI score (representing adherence to an additional WHO guideline), the pooled adjusted hazard ratios were 0.90 (95% confidence interval (CI): 0.87, 0.93) for men and women combined, 0.89 (95% CI: 0.85, 0.92) for men, and 0.90 (95% CI: 0.85, 0.95) for women. These estimates translate to an increased life expectancy of 2 years at the age of 60 years. Greater adherence to the WHO guidelines is associated with greater longevity in elderly men and women in Europe and the United States., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

This systematic review evaluated micronutrient intake inadequacy of ten micronutrients for adult ethnic minority populations residing in Europe. Pubmed was searched for studies, related references were checked and experts consulted. Ten studies were identified and six were included in the final analysis representing Albanian, Roma, Sub-Saharan African, South Asian and African-Caribbean minority groups. The Estimated Average Requirement cut point was applied to estimate inadequate intake. With the exception of a sub-Saharan African study, of seven micronutrients analysed, inadequate intakes were markedly elevated (>50 % of the population in most cases) in both genders for folate, vitamin B(12), calcium and iron (the latter in females only). A pressing need exists for intake adequacy studies with sound methodologies addressing ethnic minority groups in Europe. These populations constitute a vulnerable population for inadequate intakes and results substantiate the need for further investigation, interventions and policy measures to reduce their nutritional risk.

Background: Elevated homocysteine levels are a risk indicator for cardiovascular disease, fractures and cognitive decline. Previous studies indicated associations between homocysteine levels and medication use, including antihypertensive, lipid-lowering and antidiabetic medication. However, results were often contradictory and inconclusive. Our objective was to study the associations established previously in more detail by sub-classifying medication groups, and investigate the potential mediating role of vitamin B12 and folate status., Materials and Methods: Baseline data from the B-PROOF (B-vitamins for the PRevention Of Osteoporotic Fractures) study were used. We included 2,912 participants aged ≥65 years, with homocysteine levels of 12-50 μmol/L and creatinine levels ≤150 μmol/L, for whom self-reported medication data were available. We used multivariable linear regression models and analysis of covariance to assess the association between medication use and plasma homocysteine levels, and the potential mediation by serum vitamin B12 and folate., Results: The mean age was 74 years (standard deviation, 6.5), 50 % were women, and median homocysteine levels were 14 µmol/L [interquartile range, 13-17 µmol/L]. Higher mean homocysteine levels were observed in users vs. non-users for diuretics (15.2 vs. 14.9, p = 0.043), high-ceiling sulphonamide diuretics (16.0 vs. 14.9, p < 0.001), medication acting via the renin-angiotensin system (15.2 vs. 14.9, p = 0.029) and metformin (15.6 vs. 15.1, p = 0.006). Non-selective β-blocker use was associated with lower mean homocysteine levels (14.4 vs. 15.0, p = 0.019). Only this association was mediated by an underlying association with vitamin B12 and folate levels., Conclusion: The associations between homocysteine levels and medication use appear to be fairly modest. Our results suggest that medication use is unlikely to contribute to clinically relevant changes in plasma homocysteine levels.

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

Objective: To provide the evidence base for targeted nutrition policies to reduce the risk of micronutrient/diet-related diseases among disadvantaged populations in Europe, by focusing on: folate, vitamin B12, Fe, Zn and iodine for intake and status; and vitamin C, vitamin D, Ca, Se and Cu for intake., Design: MEDLINE and Embase databases were searched to collect original studies that: (i) were published from 1990 to 2011; (ii) involved >100 subjects; (iii) had assessed dietary intake at the individual level; and/or (iv) included best practice biomarkers reflecting micronutrient status. We estimated relative differences in mean micronutrient intake and/or status between the lowest and highest socio-economic groups to: (i) evaluate variation in intake and status between socio-economic groups; and (ii) report on data availability., Setting: Europe., Subjects: Children, adults and elderly., Results: Data from eighteen publications originating primarily from Western Europe showed that there is a positive association between indicators of socio-economic status and micronutrient intake and/or status. The largest differences were observed for intake of vitamin C in eleven out of twelve studies (5-47 %) and for vitamin D in total of four studies (4-31 %)., Conclusions: The positive association observed between micronutrient intake and socio-economic status should complement existing evidence on socio-economic inequalities in diet-related diseases among disadvantaged populations in Europe. These findings could provide clues for further research and have implications for public health policy aimed at improving the intake of micronutrients and diet-related diseases.

Background: The cross-sectional association between obesity and a lower health-related quality of life (HRQL) is clear. However, less is known about the association between changes in weight and HRQL. We examined the association between weight changes and changes in HRQL in a population-based sample of 2005 men and 2130 women aged 26-70 years., Methods: Weight was measured two or three times with 5-year intervals between 1995 and 2009, and was categorised as stable (change ≤2 kg, 40%), weight loss (19%), or weight gain 2.1-4.0 kg, 4.1-6.0 kg, or >6 kg (41%). Changes in HRQL (SF36 questionnaire, including physical and mental scales) per weight change category were compared with a stable weight using generalised estimating equations., Results: Weight gain was associated with declines of up to 5 points on five mainly physical scales and holds for different age categories. Especially for women, a dose-response relationship was observed, that is, larger weight gain was associated with larger declines in HRQL. Changes in HRQL for those with weight loss were small, but particularly on the mental scales, changes were in the negative direction compared to a stable weight., Conclusions: Weight gain and weight loss were associated with unfavourable changes in HRQL compared with a stable weight. For weight gain, this was most pronounced on the physical scales and for weight loss, although less consistent, on the mental scales.

Purpose: Maintenance of cognitive abilities is important for elderly to stay independent. With the aging of the population, the call for modifiable factors is emerging. Dietary protein might improve cognitive performance; however, this has hardly been studied. Therefore, we studied the impact of 24-week dietary protein supplementation on cognitive performance in pre-frail and frail elderly people., Methods: Pre-frail and frail elderly subjects, according to the Fried criteria, randomly received a protein drink containing 15 g protein or a placebo drink twice a day. Cognitive performance was measured at baseline and after 24 weeks by means of a sensitive neuropsychological test battery. In addition, reaction time was assessed after both 12 and 24 weeks of intervention. Domain scores were calculated for the domains episodic memory, attention and working memory, information processing speed, and executive functioning. Analyses of covariance were used to determine differences between groups. Linear mixed models were used to determine differences in reaction time over time and per treatment., Results: In total, 65 subjects (79 ± 8 years) with a median Mini-Mental State Examination score of 28 (interquartile range 26-30) were included. Reaction time improved more in the protein group (68 ms) than in the placebo group (18 ms, P = 0.03). Dietary protein had no significant effect on any of the cognitive domain scores., Conclusions: Protein supplementation might improve reaction time performance in pre-frail and frail elderly, but did not improve other cognitive functions.

A combination of high folate with low vitamin B12 plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B12 markers in relation to cognitive performance in Norwegian elderly who were unexposed to mandatory or voluntary folic acid fortification. Cognitive performance was assessed by six cognitive tests in 2203 individuals aged 72-74 years. A combined score was calculated using principal component analysis. The associations of folate concentrations, vitamin B12 markers (total vitamin B12, holotranscobalamin (holoTC) and methylmalonic acid (MMA)) and their interactions in relation to cognitive performance were evaluated by quantile regression and least-squares regression, adjusted for sex, education, apo-ɛ4 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P= 0·009) between plasma concentrations of folate and vitamin B12 in relation to cognitive performance. Plasma vitamin B12 concentrations in the lowest quartile ( < 274 pmol/l) combined with plasma folate concentrations in the highest quartile (>18·5 nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0·22, 95 % CI 0·05, 0·92). The interaction between folate and holoTC or MMA in relation to cognitive performance was not significant. In conclusion, this large study population unexposed to mandatory folic acid fortification showed that plasma folate, but not plasma vitamin B12, was associated with cognitive performance. Among the elderly participants with vitamin B12 concentrations in the lower range, the association between plasma folate and cognitive performance was strongest.

Physical activity has been proposed as one of the most effective strategies to prevent cognitive decline. Protein supplementation may exert an additive effect. The effect of resistance-type exercise training with or without protein supplementation on cognitive functioning in frail and pre-frail elderly people was assessed in a secondary analysis. Two 24-week, double-blind, randomized, placebo-controlled intervention studies were carried out in parallel. Subjects performed a resistance-type exercise program of two sessions per week (n=62) or no exercise program (n=65). In both studies, subjects were randomly allocated to either a protein (2×15 g daily) or a placebo drink. Cognitive functioning was assessed with a neuropsychological test battery focusing on the cognitive domains episodic memory, attention and working memory, information processing speed, and executive functioning. In frail and pre-frail elderly, resistance-type exercise training in combination with protein supplementation improved information processing speed (changes in domain score 0.08±0.51 versus -0.23±0.19 in the non-exercise group, p=0.04). Exercise training without protein supplementation was beneficial for attention and working memory (changes in domain scores 0.35±0.70 versus -0.12±0.69 in the non-exercise group, p=0.02). There were no significant differences among the intervention groups on the other cognitive tests or domain scores., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

To develop and evaluate the Loneliness Literacy Scale for the assessment of short-term outcomes of a loneliness prevention programme among Dutch elderly persons. Scale development was based on evidence from literature and experiences from local stakeholders and representatives of the target group. The scale was pre-tested among 303 elderly persons aged 65 years and over. Principal component analysis and internal consistency analysis were used to affirm the scale structure, reduce the number of items and assess the reliability of the constructs. Linear regression analysis was conducted to evaluate the association between the literacy constructs and loneliness. The four constructs "motivation", "self-efficacy", "perceived social support" and "subjective norm" derived from principal component analysis captured 56 % of the original variance. Cronbach's coefficient α was above 0.7 for each construct. The constructs "self-efficacy" and "perceived social support" were positively and "subjective norm" was negatively associated with loneliness. To our knowledge this is the first study developing a short-term indicator for loneliness prevention. The indicator contributes to the need of evaluating public health interventions more close to the intervention activities.

In this study we determined the short-term effects of a glucose drink and a sucrose drink compared to a placebo on cognitive performance and mood in elderly people with subjective, mild memory complaints using a randomized crossover study design. In total, 43 nondiabetic older adults with self-reported memory complaints were included. Drinks consisted of 250 ml with dissolved glucose (50 g), sucrose (100 g), or a mixture of artificial sweeteners (placebo). Multiple neuropsychological tests were performed and were combined by means of z scores into four cognitive domains: episodic memory, working memory, attention and information (processing speed), and executive functioning. Mood was assessed with the short Profile of Mood Status (s-POMS) questionnaire. Blood glucose concentrations were measured at five time points to divide participants into those with a better or poorer blood glucose recovery. Performance on the domain of attention and information processing speed was significantly better after consuming the sucrose drink (domain score of 0.06, SD = 0.91) than after the placebo drink (-0.08, SD = 0.92, p = .04). Sucrose had no effect on the other three domains, and glucose had no effect on any of the domains compared to the placebo. When dividing participants into poorer or better glucose recoverers, the beneficial effect of sucrose on attention and information processing speed was only seen in participants with a poorer recovery. After sucrose consumption, depressive feelings and tension were slightly higher than after the placebo. To conclude, 100 g sucrose, but not 50 g glucose, optimized attention and information processing speed in the short term in this study in elderly people with subjective, mild memory complaints.

As the population of elderly people is growing rapidly, the number of individuals with dementia and cognitive impairment is also increasing. One of the preventive measures against cognitive decline is diet and different dietary factors have already been investigated. This review provides an overview of studies on dietary protein and cognitive functioning and cognitive decline. Also studies on the individual amino acids that are related to brain function, tryptophan and tyrosine, are discussed. Overall, the role of dietary protein intake on cognitive functioning as well as cognitive decline has hardly been studied; we found eight observational studies and three intervention studies. More studies investigated the role of tryptophan (14 studies) and tyrosine (nine studies) in relation to cognitive functioning, but all these studies were performed in young adult populations and mostly under special conditions. Research in elderly populations, in particular, is warranted. Also more research is needed to come to definitive conclusions and specific recommendations regarding protein intake or intake of specific amino acids for maintaining optimal cognitive functioning.

Objectives: The primary objective was to explore the possible association of serum 25-hydroxyvitamin D (25[OH]D) and vitamin D intake with markers of glucose metabolism, depression, and cognitive performance. In addition, we examined to what extent the associations between vitamin D and cognitive performance were modified or mediated by fasting plasma glucose (FPG) levels., Design, Setting, and Participants: Cross-sectional study using data of 127 frail or prefrail Dutch elderly, aged 65 years or older. Frailty was defined according to the criteria of Fried and colleagues. A participant was classified prefrail when 1 to 2 criteria were met; frailty was classified as the presence of 3 or more criteria., Measurements: Associations of 25(OH)D and vitamin D intake with markers of glucose metabolism and domain-specific cognitive performance were examined by multivariable regression analyses. The possible association of vitamin D with depression and global cognitive performance was explored by Poisson regression., Results: No associations were observed for 25(OH)D with FPG, fasting plasma insulin (FPI), Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR), or depression. In contrast, serum 25(OH)D was positively associated with executive functioning (β 0.007, P = .01) and tended to be associated with information-processing speed (β 0.006, P = .06). FPG did not modify or mediate these associations. Vitamin D intake was not associated with cognitive performance, glucose metabolism, or depression., Conclusion: This cross-sectional study suggests an association of serum 25(OH)D with domain-specific cognitive performance, in particular executive functioning and possibly information-processing speed, but not with FPG, FPI, HOMA-IR, or depression. Whether these associations are causal is yet to be demonstrated., (Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Public health policy calls for intervention programmes to reduce loneliness in the ageing population. So far, numerous loneliness interventions have been developed, with effectiveness demonstrated for few of these interventions. The loneliness intervention described in this manuscript distinguishes itself from others by including multiple intervention components and targeting individuals and their environment. Intervention components included a mass media campaign, information meetings, psychosocial group courses, social activities organised by neighbours, and training of intermediaries. The aim of this manuscript is to study the effects of this integrated approach on initial and long-term outcomes., Methods: A quasi-experimental pre-test post-test intervention study was conducted among non-institutionalised elderly people aged 65 years and over to evaluate the effectiveness of the intervention by comparing the intervention community and the control community. Data on outputs, initial and long-term outcomes, and the overall goal were collected by self-administered questionnaires. Data of 858 elderly people were available for the analyses. To assess the effect linear regression analyses with adjustments for age, gender, church attendance, and mental health were used. In addition, the process evaluation provided information about the reach of the intervention components., Results: After two years, 39% of the elderly people were familiar with the intervention programme. The intervention group scored more favourably than the control group on three subscales of the initial outcome, motivation (-4.4%, 95% CI-8.3--0.7), perceived social support (-8.2%, 95% CI-13.6--2.4), and subjective norm (-11.5%, 95% CI-17.4--5.4). However, no overall effects were observed for the long-term outcome, social support, and overall goal, loneliness., Conclusions: Two years after its initiation the reach of the intervention programme was modest. Though no effect of the complex intervention was found on social support and loneliness, more favourable scores on loneliness literacy subscales were induced.

Objective: To review evidence on the associations between vitamin B12 intake and its biomarkers, vitamin B12 intake and its functional health outcomes, and vitamin B12 biomarkers and functional health outcomes., Design: A systematic review was conducted by searching electronic databases, until January 2012, using a standardized strategy developed in the EURRECA network. Relevant articles were screened and sorted based on title and abstract, then based on full text, and finally included if they met inclusion criteria. A total of sixteen articles were included in the review., Setting: Articles covered four continents: America (n 4), Europe (n 8), Africa (n 1) and Asia (n 3)., Subjects: Population groups included healthy infants, children and adolescents, and pregnant and lactating women., Results: From the total number of 5815 papers retrieved from the initial search, only sixteen were eligible according to the inclusion criteria: five for infants, five for children and adolescents, and six for pregnant and lactating women., Conclusions: Only one main conclusion could be extracted from this scarce number of references: a positive association between vitamin B12 intake and serum vitamin B12 in the infant group. Other associations were not reported in the eligible papers or the results were not provided in a consistent manner. The low number of papers that could be included in our systematic review is probably due to the attention that is currently given to research on vitamin B12 in elderly people. Our observations in the current systematic review justify the idea of performing well-designed studies on vitamin B12 in young populations.

Overweight is associated with a reduced health-related quality of life (QOL), but less is known about the impact of long-term body mass index (BMI, calculated as weight (kg)/height (m)(2)) patterns on QOL in adults. In the Dutch Doetinchem Cohort Study (1989-2009) that included 1,677 men and 1,731 women aged 20-66 years, 6 BMI patterns were defined by using 4 measurements over a 15-year period: 1) persistent healthy weight (18.5-24.9, reference pattern); 2) persistent overweight (25.0-29.9); 3) persistent obesity (≥30.0); 4) developing overweight; 5) developing obesity; and 6) switching between BMI categories. For each BMI pattern, adjusted QOL (measured on a 0-100 scale) was estimated at the end of this period. The lowest QOL was observed for persistent obesity of all BMI patterns. It was 5.0 points (P = 0.02) lower for 1 mental dimension in men and 6.2-11.6 points (P < 0.05) lower for 5 (mainly physical) dimensions in women. Developing overweight or obesity scored 1.8-6.3 points (P < 0.05) lower on 2-5 (mainly physical) dimensions. Persistent overweight hardly differed from a persistent healthy weight. In women, switching between BMI categories resulted in a lower QOL on the mental dimensions. Studying long-term BMI patterns over a 15-year period showed that persistent obesity, developing overweight, and developing obesity resulted in a lower QOL-particularly on the physical dimensions-compared with a persistent healthy weight.

Objective: The association between obesity and coronary heart disease (CHD) may have changed over time, for example due to improved pharmacological treatment of CHD risk factors. This meta-analysis of 31 prospective cohort studies explores the influence of calendar period on CHD risk associated with body mass index (BMI)., Design and Methods: The relative risks (RRs) of CHD for a five-BMI-unit increment and BMI categories were pooled by means of random effects models. Meta-regression analysis was used to examine the influence of calendar period (>1985 v ≤1985) in univariate and multivariate analyses (including mean population age as a covariate)., Results: The age, sex, and smoking adjusted RR (95% confidence intervals) of CHD for a five-BMI-unit increment was 1.28(1.22:1.34). For underweight, overweight and obesity, the RRs (compared to normal weight) were 1.11(0.91:1.36), 1.31(1.22:1.41), and 1.78(1.55:2.04), respectively. The univariate analysis indicated 31% (95%CI: -56:0) lower RR of CHD associated with a five-BMI-unit increment and a 51% (95%CI: -78: -14)) lower RR associated with obesity in studies starting after 1985 (n = 15 and 10, respectively) compared to studies starting in or before 1985 (n = 16 and 10). However, in the multivariate analysis, only mean population age was independently associated with the RRs for a five-BMI-unit increment and obesity (-29(95%CI: -55: -5)) and -31(95%CI: -66:3), respectively) per 10-year increment in mean age)., Conclusion: This study provides no consistent evidence for a difference in the association between BMI and CHD by calendar period. The mean population age seems to be the most important factor that modifies the association between the risk of CHD and BMI, in which the RR decreases with increasing age., (Copyright © 2012 The Obesity Society.)

Objective: Homocysteine has been shown to be a more accurate predictor of cardiovascular mortality in very old persons than models based on classical risk factors. Arterial stiffening is a structural abnormality involved in the pathway of cardiovascular disease. We expect this underlying pathophysiology to be a possible explanation for the association between homocysteine and cardiovascular risk, particularly in older populations., Methods: Baseline cross-sectional data of the B-PROOF study were used to determine associations between homocysteine and outcomes of vascular function and structure. The cardiovascular subgroup of the B-PROOF study was included [n = 560, 58% men, age 72.6 ± 5.5 years, median homocysteine level 14.2 μmol/l (IQR 13.0-16.6)]. We assessed carotid distensibility coefficient, carotid compliance coefficient, aortic pulse wave velocity (aPWV), augmentation index (AIx) and aortic pulse pressure (aortic PP). Associations were tested using linear regression analysis and ANCOVA and were adjusted for possible confounders including age, sex, renal function, mean arterial pressure and heart rate., Results: Ln-homocysteine was strongly associated with aPWV [β 0.005 95% confidence interval (0.001-0.009)]. Furthermore, this association was shown to be age-dependent (P = 0.02) and it was most strong in the upper tertile of age (77-98 years). No significant associations with ln-homocysteine were observed for AIx, carotid distensibility coefficient and compliance coefficient and aortic PP. Sex stratification shows the association between ln-homocysteine and aPWV is only significant in men., Conclusion: In older persons, homocysteine is associated with aortic stiffness, predominantly in the oldest old. This suggests that the strong association between homocysteine and cardiovascular mortality in the elderly may be mediated by aortic stiffness.

Objective: To compare micronutrient intakes and status in Central and Eastern Europe (CEE) with those in other European countries and with reference values., Design: Review of the micronutrient intake/status data from open access and grey literature sources from CEE., Setting: Micronutrients studied were folate, iodine, Fe, vitamin B12 and Zn (for intake and status) and Ca, Cu, Se, vitamin C and vitamin D (for intake). Intake data were based on validated dietary assessment methods; mean intakes were compared with average nutrient requirements set by the Nordic countries or the US Institute of Medicine. Nutritional status was assessed using the status biomarkers and cut-off levels recommended primarily by the WHO., Subjects: For all population groups in CEE, the mean intake and mean/median status levels were compared between countries and regions: CEE, Scandinavia, Western Europe and Mediterranean., Results: Mean micronutrient intakes of adults in the CEE region were in the same range as those from other European regions, with exception of Ca (lower in CEE). CEE children and adolescents had poorer iodine status, and intakes of Ca, folate and vitamin D were below the reference values., Conclusions: CEE countries are lacking comparable studies on micronutrient intake/status across all age ranges, especially in children. Available evidence showed no differences in micronutrient intake/status in CEE populations in comparison with other European regions, except for Ca intake in adults and iodine and Fe status in children. The identified knowledge gaps urge further research on micronutrient intake/status of CEE populations to make a basis for evidence-based nutrition policy.

Background: Homocysteine may be a modifiable risk factor for cognitive decline and brain atrophy, particularly in older persons. We examined whether homocysteine increased the risk for cognitive decline and brain atrophy, and evaluated the modifying effect of age., Methods: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study-a prospective cohort study among patients with atherosclerotic disease-longitudinal analyses were performed in 663 patients (mean age: 57 ± 9 years; follow-up: 3.9 ± 0.4 years). At baseline and follow-up, brain segmentation on magnetic resonance imaging was used to quantify relative (%) cortical, ventricular, and global brain volumes, and z-scores of memory and executive functioning were calculated. Linear regression analysis was used to estimate associations of homocysteine (per standard deviation increase) and hyperhomocysteinemia (HHCY) with brain volumes, memory, and executive functioning at follow-up, adjusted for baseline brain volume, memory, and executive functioning, respectively, and age, sex, and vascular risk factors. Furthermore, interaction terms between homocysteine and age (continuous) were added., Results: Significant interactions were observed between total plasma homocysteine (tHcy) and age with cortical, ventricular, and global brain volume (for all three measures: P < .05), and between HHCY and age with executive functioning (P = .04), and results were stratified by age. In patients aged ≥65 years, increasing tHcy level and HHCY were significantly associated with progression of ventricular enlargement (B = 0.07%, 95% confidence interval [CI]: 0.01% to 0.13% and B = 0.16%, 95% CI: 0.01% to 0.31%, respectively) and with a decline in executive function (B = -0.29, 95% CI: -0.54 to -0.04 and B = -0.84, 95% CI: -1.37 to -0.32, respectively)., Conclusion: Elevated tHcy was related to progression of ventricular enlargement and increased the risk for a decline in executive functioning in older persons., (Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Purpose: The classical consequence of vitamin D deficiency is osteomalacia, but recent insights into the function of vitamin D suggest that it may play a role in other body systems as well. The objective of this study was to examine the association between 25-hydroxyvitamin D (25(OH)D) and markers of glucose metabolism (n = 593), global cognitive functioning (n = 116) and depression (n = 118) in European elderly participating in the SENECA study. Moreover, we wanted to explore whether the observed associations of 25(OH)D with depression and global cognitive performance were mediated by fasting plasma glucose (FPG) levels., Methods: Cross-sectional associations between 25(OH)D and FPG, fasting plasma insulin (FPI) and homeostatic model assessment-insulin resistance (HOMA-IR), a marker of insulin resistance, were estimated from multiple regression analyses. Associations of 25(OH)D with global cognitive functioning (Mini Mental State Examination) and depression (Geriatric Depression Scale) were examined using Poisson regression., Results: An inverse association was observed between 25(OH)D and FPG (β-0.001), indicating a 1 % decrease in FPG per 10 nmol/L increase in 25(OH)D, but after full adjustment for demographic factors, lifestyle factors and calcium intake, this association was not statistically significant (P = 0.07). Although participants with intermediate and high serum 25(OH)D levels showed a tendency towards a lower depression score after adjustment for demographic and lifestyle factors, RR and 95 % CI: 0.73 (0.51-1.04) and 0.76 (0.52-1.11), respectively, these findings were not statistically significant., Conclusion: An inverse association of 25(OH)D with depression and FPG was observed, but this association was not statistically significant. There was no association between 25(OH)D with FPI and HOMA-IR or with global cognitive functioning. More studies are needed to further explore the possible role of vitamin D in the various body systems.

Objectives: In elderly individuals, little is known about changes in different anthropometric measures with respect to mortality. We examined the association between changes in eight anthropometric measures and mortality in an elderly population., Design: Longitudinal study including baseline measurements in 1988-1990 and repeated measures in 1993., Setting: European towns., Participants: A total of 1061 older adults born in 1913-1918 from the Survey in Europe on Nutrition and the Elderly, A Concerted Action study were included in this study., Measurements: Weight, body mass index, waist circumference, waist to hip ratio, waist to height ratio, mid-upper arm circumference (MUAC), triceps skinfold thickness, and corrected arm muscle area were taken during both measurements., Results: A Cox regression model was used to examine the association between anthropometric changes (divided into quintiles, smallest change = reference category) and all-cause and cardiovascular disease mortality over approximately 6 years of follow-up, adjusted for baseline measurement of application, age, sex, smoking, education, physical activity, and major chronic diseases. A decrease in weight (≥3.2 kg), waist circumference (≥3.1 cm), and MUAC (≥1.6 cm and 0.6-1.6 cm) were (near) significantly associated with an all-cause mortality risk of 1.48 (95% CI: 0.99-2.20), 1.52 (95% CI: 1.01-2.31), 1.81 (95% CI: 1.17-2.79), and 1.66 (95% CI: 1.10-2.49), respectively. Also for MUAC, an increase (≥1.3 cm) was significantly associated with an increased all-cause and cardiovascular disease mortality risk [hazard ratio, 1.52 (95% CI: 1.00-2.31) and 1.94 (95% CI: 1.00-3.75), respectively]., Conclusion: Associations were observed for decreases in only 3 of 8 anthropometric measures and all-cause mortality. Decreases in MUAC had the strongest association with mortality and was the only measure in which an increase also was associated with mortality. This suggests a role for MUAC in the prediction of mortality in elderly individuals., (Copyright © 2013. Published by Elsevier Inc.)

Background: Many randomized controlled trials (RCTs) and observational studies have provided information on the association between vitamin B-12 intake and biomarkers. The use of these data to estimate dose-response relations provides a useful means to summarize the body of evidence., Objective: We systematically reviewed studies that investigated vitamin B-12 intake and biomarkers of vitamin B-12 status and estimated dose-response relations with the use of a meta-analysis., Design: This systematic review included all RCTs, prospective cohort studies, nested case-control studies, and cross-sectional studies in healthy adult populations published through January 2010 that supplied or measured dietary vitamin B-12 intake and measured vitamin B-12 status as serum or plasma vitamin B-12, methylmalonic acid (MMA), or holotranscobalamin. We calculated an intake-status regression coefficient ( ) for each individual study and calculated the overall pooled and SE ( ) by using random-effects meta-analysis on a double-log scale., Results: The meta-analysis of observational studies showed a weaker slope of dose-response relations than the meta-analysis of RCTs. The pooled dose-response relation of all studies between vitamin B-12 intake and status indicated that a doubling of the vitamin B-12 intake increased vitamin B-12 concentrations by 11% (95% CI: 9.4%, 12.5%). This increase was larger for studies in elderly persons (13%) than in studies in adults (8%). The dose-response relation between vitamin B-12 intake and MMA concentrations indicated a decrease in MMA of 7% (95% CI: -10%, -4%) for every doubling of the vitamin B-12 intake. The assessment of risk of bias within individual studies and across studies indicated risk that was unlikely to seriously alter these results., Conclusion: The obtained dose-response estimate between vitamin B-12 intake and status provides complementary evidence to underpin recommendations for a vitamin B-12 intake of populations.

The EURopean micronutrient RECommendations Aligned (EURRECA) Network of Excellence explored the process of setting micronutrient recommendations to address the variance in recommendations across Europe. Work centered upon the transparent assessment of nutritional requirements via a series of systematic literature reviews and meta-analyses. In addition, the necessity of assessing nutritional requirements and the policy context of setting micronutrient recommendations was investigated. Findings have been presented in a framework that covers nine activities clustered into four stages: stage one "Defining the problem" describes Activities 1 and 2: "Identifying the nutrition-related health problem" and "Defining the process"; stage two "Monitoring and evaluating" describes Activities 3 and 7: "Establishing appropriate methods," and "Nutrient intake and status of population groups"; stage three "Deriving dietary reference values" describes Activities 4, 5, and 6: "Collating sources of evidence," "Appraisal of the evidence," and "Integrating the evidence"; stage four "Using dietary reference values in policy making" describes Activities 8 and 9: "Identifying policy options," and "Evaluating policy implementation." These activities provide guidance on how to resolve various issues when deriving micronutrient requirements and address the methodological and policy decisions, which may explain the current variation in recommendations across Europe. [Supplementary materials are available for this article. Go to the publisher's online edition of Critical Reviews in Food Science and Nutrition for the following free supplemental files: Additional text, tables, and figures.].