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© 2018 Elsevier B.V. With increasing life expectancy, age-associated cognitive impairment is an escalating problem worldwide. Inflammation is one of the features that characterises cognitive decline and can stimulate neurodegeneration. Interleukin 6 (IL-6) is a cytokine frequently associated with a pro-inflammatory phenotype and increased levels have been associated with the pathogenesis of dementia. The rs1800796 polymorphism in the promoter region of IL-6 gene was previously shown to influence IL-6 expression and therefore we hypothesised this gene polymorphism would be associated with IL-6 plasma levels and cognitive performance of older adults. The present study investigated the association of the rs1800796 polymorphism on plasma IL-6 levels and cognition in healthy older adults (n = 207, 74.6 ± 3.4 years, 51% female) that participated in a Pan-European project (MyoAge). The participants were assessed for working memory capacity, executive functioning, episodic memory and global cognition using the Cambridge Neuropsychological Test Automated Battery CANTAB. Fasting plasma IL-6 levels were measured by ELISA and genotyping was performed using the KASP assay. Results showed that the rs1800796 polymorphism was in Hardy-Weinberg equilibrium (P =.16) with the minor allele (C) showing a frequency of 6.3%. There were no differences in plasma IL-6 concentrations between the GG-homozygotes and C-allele carriers (P =.22). The C-allele carriers performed worse on a measure of executive functioning (P =.035) and had lower global cognitive scores (P =.045), compared to GG-homozygotes. These differences remained significant after accounting for age, sex and prior cognitive abilities (P <.05 for both). There were no differences in measures of memory (episodic and working) between the genotypes group. These findings suggest that the rs1800796 variant may be detrimental for executive functioning, but not memory, in healthy older adults.

© 2018 Elsevier B.V. With increasing life expectancy, age-associated cognitive impairment is an escalating problem worldwide. Inflammation is one of the features that characterises cognitive decline and can stimulate neurodegeneration. Interleukin 6 (IL-6) is a cytokine frequently associated with a pro-inflammatory phenotype and increased levels have been associated with the pathogenesis of dementia. The rs1800796 polymorphism in the promoter region of IL-6 gene was previously shown to influence IL-6 expression and therefore we hypothesised this gene polymorphism would be associated with IL-6 plasma levels and cognitive performance of older adults. The present study investigated the association of the rs1800796 polymorphism on plasma IL-6 levels and cognition in healthy older adults (n = 207, 74.6 ± 3.4 years, 51% female) that participated in a Pan-European project (MyoAge). The participants were assessed for working memory capacity, executive functioning, episodic memory and global cognition using the Cambridge Neuropsychological Test Automated Battery CANTAB. Fasting plasma IL-6 levels were measured by ELISA and genotyping was performed using the KASP assay. Results showed that the rs1800796 polymorphism was in Hardy-Weinberg equilibrium (P =.16) with the minor allele (C) showing a frequency of 6.3%. There were no differences in plasma IL-6 concentrations between the GG-homozygotes and C-allele carriers (P =.22). The C-allele carriers performed worse on a measure of executive functioning (P =.035) and had lower global cognitive scores (P =.045), compared to GG-homozygotes. These differences remained significant after accounting for age, sex and prior cognitive abilities (P <.05 for both). There were no differences in measures of memory (episodic and working) between the genotypes group. These findings suggest that the rs1800796 variant may be detrimental for executive functioning, but not memory, in healthy older adults.

© 2017 International Osteoporosis Foundation and National Osteoporosis Foundation Summary: Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with whole-body bone mineral density (WBMD) in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. Introduction: This study aims to investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during ‘healthy’ ageing. Methods: WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18–30 years; 53% female). Results: WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates (r values ranging from 0.174 to 0.254, all p < 0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD. Conclusion: Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young.

© 2017 The Authors. Background: Handgrip strength (HGS) is used to identify individuals with low muscle strength (dynapenia). The influence of the number of attempts on maximal HGS is not yet known and may differ depending on age and health status. This study aimed to assess how many attempts of HGS are required to obtain maximal HGS. Methods: Three cohorts (939 individuals) differing in age and health status were included. HGS was assessed three times and explored as continuous and dichotomous variable. Paired t-test, intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to test reproducibility of HGS. The number of individuals with misclassified dynapenia at attempts 1 and 2 with respect to attempt 3 were assessed. Results: Results showed the same pattern in all three cohorts. Maximal HGS at attempts 1 and 2 was higher than at attempt 3 on population level (P < 0.001 for all three cohorts). ICC values between all attempts were above 0.8, indicating moderate to high reproducibility. Bland-Altman analysis showed that 41.0 to 58.9% of individuals had the highest HGS at attempt 2 and 12.4 to 37.2% at attempt 3. The percentage of individuals with a maximal HGS above the gender-specific cut-off value at attempt 3 compared with attempts 1 and 2 ranged from 0 to 50.0%, with a higher percentage of misclassification in middle-aged and older populations. Conclusions: Maximal HGS is dependent on the number of attempts, independent of age and health status. To assess maximal HGS, at least three attempts are needed if HGS is considered to be a continuous variable. If HGS is considered as a discrete variable to assess dynapenia, two attempts are sufficient to assess dynapenia in younger populations. Misclassification should be taken into account in middle-aged and older populations.

© 2017 International Osteoporosis Foundation and National Osteoporosis Foundation Summary: Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with whole-body bone mineral density (WBMD) in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. Introduction: This study aims to investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during ‘healthy’ ageing. Methods: WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18–30 years; 53% female). Results: WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates (r values ranging from 0.174 to 0.254, all p < 0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD. Conclusion: Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young.

© 2017 The Authors. Background: Handgrip strength (HGS) is used to identify individuals with low muscle strength (dynapenia). The influence of the number of attempts on maximal HGS is not yet known and may differ depending on age and health status. This study aimed to assess how many attempts of HGS are required to obtain maximal HGS. Methods: Three cohorts (939 individuals) differing in age and health status were included. HGS was assessed three times and explored as continuous and dichotomous variable. Paired t-test, intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to test reproducibility of HGS. The number of individuals with misclassified dynapenia at attempts 1 and 2 with respect to attempt 3 were assessed. Results: Results showed the same pattern in all three cohorts. Maximal HGS at attempts 1 and 2 was higher than at attempt 3 on population level (P < 0.001 for all three cohorts). ICC values between all attempts were above 0.8, indicating moderate to high reproducibility. Bland-Altman analysis showed that 41.0 to 58.9% of individuals had the highest HGS at attempt 2 and 12.4 to 37.2% at attempt 3. The percentage of individuals with a maximal HGS above the gender-specific cut-off value at attempt 3 compared with attempts 1 and 2 ranged from 0 to 50.0%, with a higher percentage of misclassification in middle-aged and older populations. Conclusions: Maximal HGS is dependent on the number of attempts, independent of age and health status. To assess maximal HGS, at least three attempts are needed if HGS is considered to be a continuous variable. If HGS is considered as a discrete variable to assess dynapenia, two attempts are sufficient to assess dynapenia in younger populations. Misclassification should be taken into account in middle-aged and older populations.

Introduction: cognitive deterioration and reductions of bone health coincide with increasing age. We examine the relationship between bone composition and plasma markers of bone remodelling with measures of cognitive performance in healthy adults. Methods: this cross-sectional study included 225 old (52% women, mean age: 74.4 ± 3.3 years) and 134 young (52% women, mean age: 23.4 ± 2.7 years) adult participants from the MyoAge project. Whole body bone mineral density was measured by dualenergy X-ray absorptiometry. Blood analyses included a panel of bone-related peptides (dickkopf-1, osteoprotegerin, osteocalcin (OC), osteopontin, sclerostin, parathyroid hormone and fibroblast growth factor 23), as well as serum calcium and 25-hydroxy vitamin D assays. A selection of cognitive domains (working memory capacity, episodic memory, executive functioning and global cognition) was assessed with a standardised neuropsychological test battery. Results: adjusting for covariates and multiple testing revealed that plasma OC levels were positively associated with measures of executive functioning (β = 0.444, P < 0.001) and global cognition (β = 0.381, P = 0.001) in the older women. Discussion: these correlative results demonstrate a positive association between OC, a factor known to regulate bone remodelling, with cognitive performance in older non-demented women. Further work should address possible mechanistic interpretations in humans.

© 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.Background & aims: Consensus on the definition of malnutrition has not yet been reached. Recently, The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed a consensus definition of malnutrition. The aim of the present study was to describe the prevalence of malnutrition according to the ESPEN definition in four diverse populations. Methods: In total, 349 acutely ill middle-aged patients, 135 geriatric outpatients, 306 healthy old individuals and 179 healthy young individuals were included in the study. Subjects were screened for risk of malnutrition using the SNAQ. The ESPEN definition of malnutrition, i.e. low BMI (< 18.5 kg/m2) or a combination of unintentional weight loss and low FFMI or low BMI was applied to all subjects. Results: Screening identified 0, 0.5, 10 and 30% of the healthy young, the healthy old, the geriatric outpatients and the acutely ill middle-aged patients as being at risk of malnutrition. The prevalence of malnutrition ranged from 0% in the healthy young, 0.5% in healthy old individuals, 6% in the geriatric outpatients to 14% in the acutely ill middle-aged patients. Prevalence of low FFMI was observed in all four populations (14-33%), but concurred less frequently with weight loss (0-13%). Conclusions: Using the ESPEN definition, 0%-14% malnutrition was found in the diverse populations. Further work is needed to fully address the validity of a two-step approach, including risk assessment as an initial step in screening and defining malnutrition. Furthermore, assessing the predictive validity of the ESPEN definition is needed.

© 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.Background & aims: Consensus on the definition of malnutrition has not yet been reached. Recently, The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed a consensus definition of malnutrition. The aim of the present study was to describe the prevalence of malnutrition according to the ESPEN definition in four diverse populations. Methods: In total, 349 acutely ill middle-aged patients, 135 geriatric outpatients, 306 healthy old individuals and 179 healthy young individuals were included in the study. Subjects were screened for risk of malnutrition using the SNAQ. The ESPEN definition of malnutrition, i.e. low BMI (< 18.5 kg/m2) or a combination of unintentional weight loss and low FFMI or low BMI was applied to all subjects. Results: Screening identified 0, 0.5, 10 and 30% of the healthy young, the healthy old, the geriatric outpatients and the acutely ill middle-aged patients as being at risk of malnutrition. The prevalence of malnutrition ranged from 0% in the healthy young, 0.5% in healthy old individuals, 6% in the geriatric outpatients to 14% in the acutely ill middle-aged patients. Prevalence of low FFMI was observed in all four populations (14-33%), but concurred less frequently with weight loss (0-13%). Conclusions: Using the ESPEN definition, 0%-14% malnutrition was found in the diverse populations. Further work is needed to fully address the validity of a two-step approach, including risk assessment as an initial step in screening and defining malnutrition. Furthermore, assessing the predictive validity of the ESPEN definition is needed.

Consensus on clinically valid diagnostic criteria for sarcopenia requires a systematical assessment of the association of its candidate measures of muscle mass, muscle strength, and physical performance on one side and muscle-related clinical parameters on the other side. In this study, we systematically assessed associations between serum albumin as a muscle-related parameter and muscle measures in 172 healthy young (aged 18-30 years) and 271 old participants (aged 69-81 year) from the European MYOAGE study. Muscle measures included relative muscle mass, i.e., total- and appendicular lean mass (ALM) percentage, absolute muscle mass, i.e., ALM/height(2) and total lean mass in kilograms, handgrip strength, and walking speed. Muscle measures were standardized and analyzed in multivariate linear regression models, stratified by age. Adjustment models included age, body composition, C-reactive protein and lifestyle factors. In young participants, serum albumin was positively associated with lean mass percentage (p = 0.007) and with ALM percentage (p = 0.001). In old participants, serum albumin was not associated with any of the muscle measures. In conclusion, the association between serum albumin and muscle measures was only found in healthy young participants and the strongest for measures of relative muscle mass.

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