The Association of Vitamin D Status with Mild Cognitive Impairment and Dementia Subtypes: A Cross-Sectional Analysis in Dutch Geriatric Outpatients.

BACKGROUND: Vitamin D deficiency is associated with all-cause dementia and Alzheimer's disease (AD). At the same time, this knowledge is limited specifically for vascular dementia (VaD), while data regarding other subtypes of dementia are even more limited. OBJECTIVE: To investigate the association of 25-hydroxy vitamin D (25(OH)D) status with dementia subtypes in an outpatient geriatric population. METHODS: In a cross-sectional design, we analyzed data from 1,758 patients of an outpatient memory clinic in The Netherlands. Cognitive disorders were diagnosed by a multidisciplinary team according to international clinical standards. At each first-visit 25(OH)D levels were measured. Data were analyzed using ANCOVA in four models with age, gender, BMI, education, alcohol, smoking, season, polypharmacy, calcium, eGFR, and glucose as co-variates. 25(OH)D was treated as a continuous square rooted (sqr) variable. RESULTS: In the fully adjusted model, reduced 25(OH)D serum levels (sqr) were found in AD (estimated mean 7.77±0.11 CI95% 7.55-7.99): and in VaD (estimated mean 7.60±0.16 CI95% 7.28-7.92) patients compared to no-dementia (ND) patients (estimated mean 8.27±0.09 CI95% 8.10-8.45) (ND-AD: p = 0.006, CI95% 0.08-0.92.; ND-VaD p = 0.004 CI95% 0.13-1.22). We did not find differences in 25(OH)D levels of mild cognitive impairment (MCI) or other dementia patients compared to ND patients, nor differences in comparing dementia subtypes. CONCLUSION: We observed significantly lower 25(OH)D serum levels in both AD and VaD patients compared to no-dementia patients, but no significant differences between MCI and Lewy body and mixed dementia subtypes in this cross-sectional study of a geriatric outpatient clinic population.

Protein intake and bone mineral density: Cross-sectional relationship and longitudinal effects in older adults.

BACKGROUND: There are several mechanisms via which increased protein intake might maintain or improve bone mineral density (BMD), but current evidence for an association or effect is inconclusive. The objectives of this study were to investigate the association between dietary protein intake (total, plant and animal) with BMD (spine and total body) and the effects of protein supplementation on BMD. METHODS: Individual data from four trials that included either (pre-)frail, undernourished or healthy older adults (aged ≥65 years) were combined. Dietary intake was assessed with food records (2, 3 or 7 days) and BMD with dual-energy X-ray absorptiometry (DXA). Associations and effects were assessed by adjusted linear mixed models. RESULTS: A total of 1570 participants [57% women, median (inter-quartile range): age 71 (68-75) years] for which at least total protein intake and total body BMD were known were included in cross-sectional analyses. In fully adjusted models, total protein intake was associated with higher total body and spine BMD [beta (95% confidence interval): 0.0011 (0.0006-0.0015) and 0.0015 (0.0007-0.0023) g/cm2 , respectively]. Animal protein intake was associated with higher total body and spine BMD as well [0.0011 (0.0007-0.0016) and 0.0017 (0.0010-0.0024) g/cm2 , respectively]. Plant protein intake was associated with a lower total body and spine BMD [-0.0010 (-0.0020 to -0.0001) and -0.0019 (-0.0034 to -0.0004) g/cm2 , respectively]. Associations were similar between sexes. Participants with a high ratio of animal to plant protein intake had higher BMD. In participants with an adequate calcium intake and sufficient serum 25(OH)D concentrations, the association between total protein intake with total body and spine BMD became stronger. Likewise, the association between animal protein intake with total body BMD was stronger. In the longitudinal analyses, 340 participants [58% women, median (inter-quartile range): age 75 (70-81) years] were included. Interventions of 12 or 24 weeks with protein supplementation or protein supplementation combined with resistance exercise did not lead to significant improvements in BMD. CONCLUSIONS: An association between total and animal protein intake with higher BMD was found. In contrast, plant protein intake was associated with lower BMD. Research is warranted to further investigate the added value of dietary protein alongside calcium and vitamin D for BMD improvement, especially in osteopenic or osteoporotic individuals. Moreover, more research on the impact of a plant-based diet on bone health is needed.

Development of the ADFICE_IT Models for Predicting Falls and Recurrent Falls in Community-Dwelling Older Adults: Pooled Analyses of European Cohorts With Special Attention to Medication.

BACKGROUND: Use of fall prevention strategies requires detection of high-risk patients. Our goal was to develop prediction models for falls and recurrent falls in community-dwelling older adults and to improve upon previous models by using a large, pooled sample and by considering a wide range of candidate predictors, including medications. METHODS: Harmonized data from 2 Dutch (LASA, B-PROOF) and 1 German cohort (ActiFE Ulm) of adults aged ≥65 years were used to fit 2 logistic regression models: one for predicting any fall and another for predicting recurrent falls over 1 year. Model generalizability was assessed using internal-external cross-validation. RESULTS: Data of 5 722 participants were included in the analyses, of whom 1 868 (34.7%) endured at least 1 fall and 702 (13.8%) endured a recurrent fall. Positive predictors for any fall were: educational status, depression, verbal fluency, functional limitations, falls history, and use of antiepileptics and drugs for urinary frequency and incontinence; negative predictors were: body mass index (BMI), grip strength, systolic blood pressure, and smoking. Positive predictors for recurrent falls were: educational status, visual impairment, functional limitations, urinary incontinence, falls history, and use of anti-Parkinson drugs, antihistamines, and drugs for urinary frequency and incontinence; BMI was a negative predictor. The average C-statistic value was 0.65 for the model for any fall and 0.70 for the model for recurrent falls. CONCLUSION: Compared with previous models, the model for recurrent falls performed favorably while the model for any fall performed similarly. Validation and optimization of the models in other populations are warranted.

Genetic variants modify the associations of concentrations of methylmalonic acid, vitamin B-12, vitamin B-6, and folate with bone mineral density.

BACKGROUND: Elevated plasma homocysteine has been found to be associated with an increased risk of osteoporosis, especially hip and vertebral fractures. The plasma concentration of homocysteine is dependent on the activities of several B vitamin-dependent enzymes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and cystathionine ß-synthase (CBS). OBJECTIVES: We investigated whether genetic variants in some of the genes involved in 1 carbon metabolism modify the association of B vitamin-related measures with bone mineral density (BMD) and strength. METHODS: We measured several B vitamins and biomarkers in participants of the Framingham Offspring Study, and performed analyses of methylmalonic acid (MMA) continuously and <210 nmol/L; pyridoxal-5'-phosphate; vitamin B-12 continuously and ≥258 pmol/L; and folate. The outcomes of interest included areal and volumetric BMD, measured by DXA and quantitative computed tomography (QCT), respectively. We evaluated associations between the bone measures and interactions of single nucleotide polymorphism with a B vitamin or biomarker in Framingham participants (n = 4310 for DXA and n = 3127 for QCT). For analysis of DXA, we validated the association results in the B-PROOF cohort (n = 1072). Bonferroni-corrected locus-wide significant thresholds were defined to account for multiple testing. RESULTS: The interactions between rs2274976 and vitamin B-12 and rs34671784 and MMA <210 nmol/L were associated with lumbar spine BMD, and the interaction between rs6586281 and vitamin B-12 ≥258 pmol/L was associated with femoral neck BMD. For QCT-derived traits, 62 interactions between genetic variants and B vitamins and biomarkers were identified. CONCLUSIONS: Some genetic variants in the 1-carbon methylation pathway modify the association of B vitamin and biomarker concentrations with bone density and strength.  These interactions require further replication and functional validation for a mechanistic understanding of the role of the 1-carbon metabolism pathway on BMD and risks of fracture.

Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women.

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10-17), arthritis (GDF5 p = 4 × 10-13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.

Beneficial Role of Replacing Dietary Saturated Fatty Acids with Polyunsaturated Fatty Acids in the Prevention of Sarcopenia: Findings from the NU-AGE Cohort.

Dietary fat subtypes may play an important role in the regulation of muscle mass and function during ageing. The aim of the present study was to determine the impact of isocaloric macronutrient substitutions, including different fat subtypes, on sarcopenia risk in older men and women, while accounting for physical activity (PA) and metabolic risk. A total of 986 participants, aged 65-79 years, completed a 7-day food record and wore an accelerometer for a week. A continuous sex-specific sarcopenia risk score (SRS), including skeletal muscle mass assessed by dual-energy X-ray absorptiometry (DXA) and handgrip strength, was derived. The impact of the isocaloric replacement of saturated fatty acids (SFAs) by either mono- (MUFAs) or poly-unsaturated (PUFAs) fatty acids on SRS was determined using regression analysis based on the whole sample and stratified by adherence to a recommended protein intake (1.1 g/BW). Isocaloric reduction of SFAs for the benefit of PUFAs was associated with a lower SRS in the whole population, and in those with a protein intake below 1.1 g/BW, after accounting for age, smoking habits, metabolic disturbances, and adherence to PA guidelines. The present study highlighted the potential of promoting healthy diets with optimised fat subtype distribution in the prevention of sarcopenia in older adults.

Associations between the Intake of Different Types of Dairy and Cognitive Performance in Dutch Older Adults: The B-PROOF Study.

Various dairy nutrients have been associated with cognitive performance. Several observational studies have explored associations between the intake of total dairy or some dairy subgroups and cognitive performance. However, studies on the potential impact of a broad variety of dairy subclasses are scarce. We examined cross-sectional associations between a wide assortment of dairy products and cognitive performance. A total of 619 Dutch community-dwelling adults aged ≥65 years completed a semi-quantitative Food Frequency Questionnaire. Cognitive performance was assessed with an extensive neuropsychological test battery; the tests were clustered into cognitive domains using z-scores. Linear and logistic regression analyses, adjusted for age, sex, BMI, education, smoking, alcohol consumption, habitual physical activity, total energy intake, and dietary factors, were performed to quantify the associations. The Benjamini-Hochberg method was used to correct for multiple testing. After full adjustment, higher skimmed dairy (ß ± SD: 0.05 ± 0.02, p = 0.06), fermented dairy (0.04 ± 0.02, p = 0.09), and buttermilk (0.08 ± 0.03, p = 0.19) consumption were associated with better executive functioning. Logistic regression analyses indicated that a 30 g increase in Dutch cheese intake was associated with a 33% lower probability of poor information processing speed (PR = 0.67, 95% CI 0.47-0.97). No associations were observed between dairy consumption and attention and working memory or episodic memory.

Changing from a Western to a Mediterranean-style diet does not affect iron or selenium status: results of the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) 1-year randomized clinical trial in elderly Europeans.

BACKGROUND: Mediterranean diets limit red meat consumption and increase intakes of high-phytate foods, a combination that could reduce iron status. Conversely, higher intakes of fish, a good source of selenium, could increase selenium status. OBJECTIVES: A 1-y randomized controlled trial [New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE)] was carried out in older Europeans to investigate the effects of consuming a Mediterranean-style diet on indices of inflammation and changes in nutritional status. METHODS: Selenium and iron intakes and status biomarkers were measured at baseline and after 1 y in 1294 people aged 65-79 y from 5 European countries (France, Italy, the Netherlands, Poland, and the United Kingdom) who had been randomly allocated either to a Mediterranean-style diet or to remain on their habitual, Western diet. RESULTS: Estimated selenium intakes increased significantly with the intervention group (P < 0.01), but were not accompanied by changes in serum selenium concentrations. Iron intakes also increased (P < 0.001), but there was no change in iron status. However, when stratified by study center, there were positive effects of the intervention on iron status for serum ferritin for participants in Italy (P = 0.04) and France (P = 0.04) and on soluble transferrin receptor (sTfR) for participants in Poland (P < 0.01). Meat intake decreased and fish intake increased to a greater degree in the intervention group, relative to the controls (P < 0.01 for both), but the overall effects of the intervention on meat and fish intakes were mainly driven by data from Poland and France. Changes in serum selenium in the intervention group were associated with greater changes in serum ferritin (P = 0.01) and body iron (P = 0.01), but not sTfR (P = 0.73); there were no study center × selenium status interactions for the iron biomarkers. CONCLUSIONS: Consuming a Mediterranean-style diet for 1 y had no overall effect on iron or selenium status, although there were positive effects on biomarkers of iron status in some countries. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012.

Protein supplementation improves lean body mass in physically active older adults: a randomized placebo-controlled trial.

BACKGROUND: An inadequate protein intake may offset the muscle protein synthetic response after physical activity, reducing the possible benefits of an active lifestyle for muscle mass. We examined the effects of 12 weeks of daily protein supplementation on lean body mass, muscle strength, and physical performance in physically active older adults with a low habitual protein intake (<1.0 g/kg/day). METHODS: A randomized double-blinded controlled trial was performed among 116 physically active older adults [age 69 (interquartile range: 67-73) years, 82% male] who were training for a 4 day walking event of 30, 40, or 50 km/day. Participants were randomly allocated to either 31 g of milk protein or iso-caloric placebo supplementation for 12 weeks. Body composition (dual-energy X-ray absorptiometry), strength (isometric leg extension and grip strength), quadriceps contractile function, and physical performance [Short Physical Performance Battery, Timed Up-and-Go test, and cardiorespiratory fitness (Åstrand-Rhyming submaximal exercise test)] were measured at baseline and after 12 weeks. We assessed vitamin D status and markers of muscle damage and renal function in blood and urine samples before and after intervention. RESULTS: A larger increase in relative lean body mass was observed in the protein vs. placebo group (∆0.93 ± 1.22% vs. ∆0.44 ± 1.40%, PInteraction  = 0.046). Absolute and relative fat mass decreased more in the protein group than in the placebo group (∆-0.90 ± 1.22 kg vs. ∆-0.31 ± 1.28 kg, PInteraction  = 0.013 and ∆-0.92 ± 1.19% vs. ∆-0.39 ± 1.36%, PInteraction  = 0.029, respectively). Strength and contractile function did not change in both groups. Gait speed, chair-rise ability, Timed Up-and-Go, and cardiorespiratory fitness improved in both groups (P < 0.001), but no between-group differences were observed. Serum urea increased in the protein group, whereas no changes were observed in the placebo group (PInteraction  < 0.001). No between-group differences were observed for vitamin D status, muscle damage, and renal function markers. CONCLUSIONS: In physically active older adults with relatively low habitual dietary protein consumption, an improvement in physical performance, an increase in lean body mass, and a decrease in fat mass were observed after walking exercise training. A larger increase in relative lean body mass and larger reduction in fat mass were observed in participants receiving 12 weeks of daily protein supplementation compared with controls, whereas this was not accompanied by differences in improvements between groups in muscle strength and physical performance.

Nandrolone decanoate administration does not attenuate muscle atrophy during a short period of disuse.

BACKGROUND: A few days of bed rest or immobilization following injury, disease, or surgery can lead to considerable loss of skeletal muscle mass and strength. It has been speculated that such short, successive periods of muscle disuse may be largely responsible for the age-related loss of muscle mass throughout the lifespan. OBJECTIVE: To assess whether a single intramuscular injection of nandrolone decanoate prior to immobilization can attenuate the loss of muscle mass and strength in vivo in humans. DESIGN, SETTING AND PARTICIPANTS: Thirty healthy (22 ± 1 years) men were subjected to 7 days of one-legged knee immobilization by means of a full leg cast with (NAD, n = 15) or without (CON, n = 15) prior intramuscular nandrolone decanoate injection (200 mg). MEASURES: Before and immediately after immobilization, quadriceps muscle cross-sectional area (CSA) (by means of single-slice computed tomography (CT) scans of the upper leg) and one-legged knee extension strength (one-repetition maximum [1-RM]) were assessed for both legs. Furthermore, muscle biopsies from the immobilized leg were taken before and after immobilization to assess type I and type II muscle fiber cross-sectional area. RESULTS: Quadriceps muscle CSA decreased during immobilization in both CON and NAD (-6 ± 1% and -6 ± 1%, respectively; main effect of time P<0.01), with no differences between the groups (time × treatment interaction, P = 0.59). Leg muscle strength declined following immobilization (-6 ± 2% in CON and -7 ± 3% in NAD; main effect of time, P<0.05), with no differences between groups (time × treatment interaction, P = 0.55). CONCLUSIONS: This is the first study to report that nandrolone decanoate administration does not preserve skeletal muscle mass and strength during a short period of leg immobilization in vivo in humans.

Folic Acid and Vitamin B12 Supplementation and the Risk of Cancer: Long-term Follow-up of the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) Trial.

BACKGROUND: Folic acid and vitamin B12 play key roles in one-carbon metabolism. Disruption of one-carbon metabolism may be involved in the risk of cancer. Our aim was to assess the long-term effect of supplementation with both folic acid and vitamin B12 on the incidence of overall cancer and on colorectal cancer in the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial. METHODS: Long-term follow-up of B-PROOF trial participants (N = 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 µg) and vitamin B12 (500 µg) versus placebo on fracture incidence. Information on cancer incidence was obtained from the Netherlands cancer registry (Integraal Kankercentrum Nederland), using the International Statistical Classification of Disease (ICD-10) codes C00-C97 for all cancers (except C44 for skin cancer), and C18-C20 for colorectal cancer. RESULTS: Allocation to B vitamins was associated with a higher risk of overall cancer [171 (13.6%) vs. 143 (11.3%); HR 1.25; 95% confidence interval (CI), 1.00-1.53, P = 0.05]. B vitamins were significantly associated with a higher risk of colorectal cancer [43(3.4%) vs. 25(2.0%); HR 1.77; 95% CI, 1.08-2.90, P = 0.02]. CONCLUSIONS: Folic acid and vitamin B12 supplementation was associated with an increased risk of colorectal cancer. IMPACT: Our findings suggest that folic acid and vitamin B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin B12 are needed to evaluate whether folic acid and vitamin B12 supplementation should be limited to patients with a known indication, such as a proven deficiency.

Are Nutrition-Related Knowledge and Attitudes Reflected in Lifestyle and Health Among Elderly People? A Study Across Five European Countries.

Background: Nutrition-related knowledge (NRK) and nutrition-related attitudes (NRAs) are necessary for dietary changes toward healthier dietary patterns. In turn, healthier dietary patterns can be beneficial in maintaining health of older adults. Therefore, the aim of this cross-sectional study was to investigate whether NRK and NRAs were associated with lifestyle and health features among older adults (65+ years) from five European countries (France, Italy, Poland, the Netherlands and United Kingdom). Methods: Within the European project NU-AGE, 1,144 healthy elderly volunteers (65-79 years) were randomly assigned to two groups: intervention (NU-AGE diet) or control. After 1-year of follow-up, both NRK and NRAs were assessed during exit interviews, in combination with a number of lifestyle and health variables (e.g., physical activity, smoking, alcohol use, BMI, self-assessed health status). Multivariable linear regression models were used in data analysis. Results: In the NU-AGE study sample, good NRK was associated with lower BMI and higher physical activity. More positive NRAs were related to lower BMI and self-reported very good or good appetite. Moreover, both NRK and NRAs were associated with some socio-economic determinants, like financial situation, age, education, living area (for NRK), and country (for NRAs). Participants in the intervention group showed a better NRK (ß = 0.367 [95% CI: 0.117; 0.617], p = 0.004) and more positive NRAs (ß = 0.838 [95% CI: 0.318; 1.358], p = 0.002) than those in the control group. Higher self-evaluated knowledge was also significantly related to more positive NRAs (p < 0.001). The most popular sources of nutrition information were food labels, books and magazines on health, the dietitian and the doctor's office, although their importance varied significantly among countries, and, to a lesser extent, between women and men and between intervention and control group. Conclusion: Higher NRK and NRA scores were associated with lower BMI and higher physical activity level. Therefore, a good nutrition-related knowledge and positive nutrition-related attitudes can strongly and positively influence the health status and quality of life among the older population. These results offer a great opportunity for policy makers to implement educational programs in order to counteract the epidemic of obesity and to improve the health span of European population.

Determinants of Behaviour Change in a Multi-Component Telemonitoring Intervention for Community-Dwelling Older Adults.

Optimal diet quality and physical activity levels are essential for healthy ageing. This study evaluated the effects of a multi-component telemonitoring intervention on behavioural determinants of diet quality and physical activity in older adults, and assessed the mediating role of these determinants and two behaviour change techniques in the intervention's effects. A non-randomised controlled design was used including 214 participants (average age 80 years) who were allocated to the intervention or control group based on municipality. The six-month intervention consisted of self-measurements of nutritional outcomes and physical activity, education, and follow-up by a nurse. The control group received regular care. Measurements took place at baseline, after 4.5 months and at the end of the study. The intervention increased self-monitoring and improved knowledge and perceived behavioural control for physical activity. Increased self-monitoring mediated the intervention's effect on diet quality, fruit intake, and saturated fatty acids intake. Improved knowledge mediated the effect on protein intake. Concluding, this intervention led to improvements in behavioural determinants of diet quality and physical activity. The role of the hypothesised mediators was limited. Insight into these mechanisms of impact provides directions for future development of nutritional eHealth interventions for older adults, in which self-monitoring may be a promising behaviour change technique. More research is necessary into how behaviour change is established in telemonitoring interventions for older adults.

Protein Intake and Distribution in Relation to Physical Functioning and Quality of Life in Community-Dwelling Elderly People: Acknowledging the Role of Physical Activity.

Increasing total protein intake and a spread protein intake distribution are potential strategies to attenuate sarcopenia related loss of physical function and quality of life. The aim of this cross-sectional study was to investigate whether protein intake and protein intake distribution are associated with muscle strength, physical function and quality of life in community-dwelling elderly people with a wide range of physical activity. Dietary and physical activity data were obtained from two studies (N = 140, age 81 ± 6, 64% male), with the following outcome measures: physical functioning (Short Physical Performance Battery (SPPB), comprising balance, gait speed and chair rise tests), handgrip strength and quality of life (EQ-5D-5L). Protein intake distribution was calculated for each participant as a coefficient of variance (CV = SD of grams of protein intake per main meal divided by the average total amount of proteins (grams) of the main meals). Based on the CV, participants were divided into tertiles and classified as spread, intermediate or pulse. The average total protein intake was 1.08 ± 0.29 g/kg/day. Total protein intake was not associated with outcome measures using multivariate regression analyses. Individuals with a spread protein diet during the main meals (CV < 0.43) had higher gait speed compared to those with an intermediate diet (CV 0.43⁻0.62) (ß = -0.42, p = 0.035), whereas a spread and pulse protein diet were not associated with SPPB total score, chair rise, grip strength and Quality-Adjusted Life Year (QALY). The interaction of higher physical activity and higher total protein intake was significantly associated with higher quality of life (ß = 0.71, p = 0.049). While this interaction was not associated with SPPB or grip strength, the association with quality of life emphasizes the need for a higher total protein intake together with an active lifestyle in the elderly.

Attenuated strength gains during prolonged resistance exercise training in older adults with high inflammatory status.

OBJECTIVES: Chronic systemic low grade inflammation is associated with the age-related loss of muscle mass. Resistance exercise has been suggested to reduce or lower chronic systemic low grade inflammation. However, systemic chronic low-grade inflammation may adversely affect the adaptive response to exercise training. We investigated the effect of resistance exercise training on systemic chronic low-grade inflammation in older adults. In addition, we studied the association between systemic chronic low-grade inflammation and the adaptive response to exercise training. DESIGN/SETTING/PARTICIPANTS: Frail and pre-frail older adults (61 subjects) performed 24 weeks of progressive resistance exercise training. Frailty was assessed using the Fried frailty criteria. MEASUREMENTS: Lean body mass (DXA), strength (1RM), circulating levels of IL-1ß, IL-6, IL-8 and TNF-α were measured prior to exercise training, after 12 weeks of training, and after 24 weeks of training. RESULTS: Prolonged progressive resistance exercise training did not affect circulating levels of IL-6, IL-8 and TNF-α. However, exercise training led to a small but significant increase of 0.052 pg/mL in IL-1ß. Higher circulating levels of TNF-α, IL-8 and IL-6 during the training period were negatively associated with strength gains for the leg press. A doubling of plasma TNF-α, IL-8 or IL-6 resulted in reduced strength gains for leg press with coefficients of -3.52, -3.42 and -1.54 respectively. High levels of circulating TNF-α were also associated with decreased strength gains for the leg extension (coefficient -1.50). Inflammatory cytokines did not appear to have an effect on gains in lean mass. CONCLUSION: Our findings suggest that increased levels of plasma cytokines (TNF-α, IL-6 and IL-8) are associated with lower strength gains during resistance exercise training.

Self-rated health and all-cause and cause-specific mortality of older adults: Individual data meta-analysis of prospective cohort studies in the CHANCES Consortium.

OBJECTIVES: To evaluate, among the elderly, the association of self-rated health (SRH) with mortality, and to identify determinants of self-rating health as "at-least-good". STUDY DESIGN: Individual data on SRH and important covariates were obtained for 424,791 European and United States residents, ≥60 years at recruitment (1982-2008), in eight prospective studies in the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES). In each study, adjusted mortality ratios (hazard ratios, HRs) in relation to SRH were calculated and subsequently combined with random-effect meta-analyses. MAIN OUTCOME MEASURES: All-cause, cardiovascular and cancer mortality. RESULTS: Within the median 12.5 years of follow-up, 93,014 (22%) deaths occurred. SRH "fair" or "poor" vs. "at-least-good" was associated with increased mortality: HRs 1.46 (95% CI 1·23-1.74) and 2.31 (1.79-2.99), respectively. These associations were evident: for cardiovascular and, to a lesser extent, cancer mortality, and within-study, within-subgroup analyses. Accounting for lifestyle, sociodemographic, somatometric factors and, subsequently, for medical history explained only a modest amount of the unadjusted associations. Factors favourably associated with SRH were: sex (males), age (younger-old), education (high), marital status (married/cohabiting), physical activity (active), body mass index (non-obese), alcohol consumption (low to moderate) and previous morbidity (absence). CONCLUSION: SRH provides a quick and simple tool for assessing health and identifying groups of elders at risk of early mortality that may be useful also in clinical settings. Modifying determinants of favourably rating health, e.g. by increasing physical activity and/or by eliminating obesity, may be important for older adults to "feel healthy" and "be healthy".

Creatine Loading Does Not Preserve Muscle Mass or Strength During Leg Immobilization in Healthy, Young Males: A Randomized Controlled Trial.

BACKGROUND: A short period of leg immobilization leads to rapid loss of muscle mass and strength. Creatine supplementation has been shown to increase lean body mass in active individuals and can be used to augment gains in muscle mass and strength during prolonged resistance-type exercise training. OBJECTIVE: Our objective was to investigate whether creatine loading can attenuate the loss of muscle mass and strength during short-term leg immobilization. METHODS: Healthy young men (n = 30; aged 23 ± 1 years; body mass index [BMI] 23.3 ± 0.5 kg/m-2) were randomly assigned to either a creatine or a placebo group. Subjects received placebo or creatine supplements (20 g/d) for 5 days before one leg was immobilized by means of a full-leg cast for 7 days. Muscle biopsies were taken before creatine loading, prior to and immediately after leg immobilization, and after 7 days of subsequent recovery. Quadriceps cross-sectional area (CSA) (computed tomography [CT] scan) and leg muscle strength (one-repetition maximum [1-RM] knee extension) were assessed before and immediately after immobilization and after 1 week of recovery. Data were analyzed using repeated measures analysis of variance (ANOVA). Data are presented consistently as mean ± standard error of the mean (SEM). RESULTS: There was a significant overall increase in muscle total creatine content following the 5-day loading phase (p = 0.049), which appeared driven by an increase in the creatine group (from 90 ± 9 to 107 ± 4 mmol/kg-1 dry muscle) with no apparent change in the placebo group (from 88 ± 4 to 90 ± 3 mmol/kg-1; p = 0.066 for time × treatment interaction). Quadriceps muscle CSA had declined by 465 ± 59 and 425 ± 69 mm2 (p < 0.01) in the creatine and placebo group, respectively, with no differences between groups (p = 0.76). Leg muscle strength decreased from 56 ± 4 to 53 ± 4 kg in the creatine and from 59 ± 3 to 53 ± 3 kg in the placebo group, with no differences between groups (p = 0.20). Muscle fiber size did not change significantly over time in either group (p > 0.05). When non-responders to creatine loading were excluded (n = 6), responders (n = 8; total creatine content increasing from 70 to 106 mmol/kg-1) showed similar findings, with no signs of preservation of muscle mass or strength during immobilization. During the subsequent recovery phase, no differences in muscle mass or strength were found between the two groups (p > 0.05). CONCLUSION: Creatine supplementation prior to and during leg immobilization does not prevent or attenuate the loss of muscle mass or strength during short-term muscle disuse. NIH Clinical Trial Registration Number: NCT01894737 ( http://www.clinicaltrials.gov/ ).

Adherence to the WCRF/AICR Dietary Recommendations for Cancer Prevention and Risk of Cancer in Elderly from Europe and the United States: A Meta-Analysis within the CHANCES Project.

BACKGROUND: It is unknown whether dietary recommendations for cancer prevention are applicable to the elderly. We analyzed WCRF/AICR recommendations in cohorts of European and U.S. adults ages 60 years and above. METHODS: Individual participant data meta-analysis included 362,114 participants (43% women), from seven prospective cohort studies, free from cancer at enrollment. The WCRF/AICR diet score was based on: (i) energy-dense foods and sugary drinks, (ii) plant foods, (iii) red and processed meat, and (iv) alcoholic drinks. Cox proportional hazards regression was used to examine the association between the diet score and cancer risks. Adjusted, cohort-specific HRs were pooled using random-effects meta-analysis. Risk advancement periods (RAP) were calculated to quantify the time period by which the risk of cancer was postponed among those adhering to the recommendations. RESULTS: After a median follow-up of 11 to 15 years across cohorts, 70,877 cancer cases were identified. Each one-point increase in the WCRF/AICR diet score [range, 0 (no) to 4 (complete adherence)] was significantly associated with a lower risk of total cancer [HR, 0.94; 95% confidence interval (CI), 0.92-0.97], cancers of the colorectum (HR, 0.84; 95% CI, 0.80-0.89) and prostate (HR, 0.94; 95% CI, 0.92-0.97), but not breast or lung. Adherence to an additional component of the WCRF/AICR diet score significantly postponed the incidence of cancer at any site by 1.6 years (RAP, -1.6; 95% CI, -4.09 to -2.16). CONCLUSIONS: Adherence to WCRF/AICR dietary recommendations is associated with lower risk of cancer among older adults. IMPACT: Dietary recommendations for cancer prevention are applicable to the elderly. Cancer Epidemiol Biomarkers Prev; 26(1); 136-44. ©2016 AACR.

Expression of protocadherin gamma in skeletal muscle tissue is associated with age and muscle weakness.

BACKGROUND: The skeletal muscle system plays an important role in the independence of older adults. In this study we examine differences in the skeletal muscle transcriptome between healthy young and older subjects and (pre-)frail older adults. Additionally, we examine the effect of resistance-type exercise training on the muscle transcriptome in healthy older subjects and (pre-)frail older adults. METHODS: Baseline transcriptome profiles were measured in muscle biopsies collected from 53 young, 73 healthy older subjects, and 61 frail older subjects. Follow-up samples from these frail older subjects (31 samples) and healthy older subjects (41 samples) were collected after 6 months of progressive resistance-type exercise training. Frail older subjects trained twice per week and the healthy older subjects trained three times per week. RESULTS: At baseline genes related to mitochondrial function and energy metabolism were differentially expressed between older and young subjects, as well as between healthy and frail older subjects. Three hundred seven genes were differentially expressed after training in both groups. Training affected expression levels of genes related to extracellular matrix, glucose metabolism ,and vascularization. Expression of genes that were modulated by exercise training was indicative of muscle strength at baseline. Genes that strongly correlated with strength belonged to the protocadherin gamma gene cluster (r = -0.73). CONCLUSIONS: Our data suggest significant remaining plasticity of ageing skeletal muscle to adapt to resistance-type exercise training. Some age-related changes in skeletal muscle gene expression appear to be partially reversed by prolonged resistance-type exercise training. The protocadherin gamma gene cluster may be related to muscle denervation and re-innervation in ageing muscle.

Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium.

BACKGROUND: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality. METHODS: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs. RESULTS: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking. CONCLUSIONS: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.