The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data.

Omentin-1 (also known as intelectin-1) is a recently identified visceral adipose tissue-derived cytokine that is inversely related to obesity. Our previous study showed that omentin-1 inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells (CVSMCs) in vitro. This study was undertaken to investigate the effects of omentin-1 on arterial calcification and bone metabolism in vivo. In vitro, omentin-1 stimulated production of osteoprotegerin (OPG) and inhibited production of receptor activator for nuclear factor κB ligand (RANKL) in both CVSMCs and osteoblasts. In vivo, adenovirus-mediated over-expression of omentin-1 attenuated arterial calcification and bone loss in OPG^−/− mice. All these in vitro and in vivo actions were abrogated by blockade of the PI3K–Akt signalling pathway. Furthermore, omentin-1 reduced serum levels of RANKL, tartarate-resistant acid phosphatase-5b and osteocalcin, all of which are increased dramatically in OPG^−/− mice. These data suggest that omentin-1 ameliorates arterial calcification and bone loss in vivo through the regulation of the RANK signalling pathway.

Amino acids have emerged as novel biomarkers for predicting type 2 diabetes (T2D), but the epidemiologic data linking circulating amino acid profiles with T2D are sparse in Asian populations. We conducted a nested case-control study within a cohort of 4,754 nondiabetic Japanese employees who attended a comprehensive health checkup in 2008–2009 and agreed to provide blood samples. During a 5-year follow-up, incident T2D cases were ascertained based on plasma glucose, glycated hemoglobin, and self-report. Two controls matched to each case on sex, age, and the date of serum sampling were randomly selected by using density sampling, resulting in 284 cases and 560 controls with amino acid measures. High concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, alanine, glutamate, ornithine, and lysine were associated with an increased risk of incident T2D, in a linear manner. High glutamine concentrations were associated with a decreased risk of incident T2D. Further adjustment for the homeostasis model assessment of insulin resistance attenuated these associations. Overall, these amino acids may be novel useful biomarkers in the identification of people at risk of T2D before overt symptoms. Insulin resistance may account for or mediate the relationship between these amino acids and risk of incident T2D.

This study aimed to examine the associations between time spent in prolonged and non-prolonged sedentary bouts and the development of metabolic syndrome. We used data from a prospective study of Japanese workers. Baseline examination was conducted between 2010 and 2011. A total of 430 office workers (58 women) aged 40-64 years without metabolic syndrome were followed up by annual health checkups until 2014. Metabolic syndrome was defined as having ≥ 3 out of 5 diagnostic criteria from the Joint Interim Statement 2009 definition. Sedentary time was assessed using a tri-axial accelerometer. Time spent in total, prolonged (accumulated ≥ 30 min) and non-prolonged sedentary bouts (accumulated < 30 min) was calculated. Cox proportional hazards models were used to estimate the risk of developing metabolic syndrome. During a median follow-up of 3 years, 83 participants developed metabolic syndrome. After adjustment for age, sex, education, smoking, and family income, positive associations were observed between time spent in prolonged sedentary bouts and the development of metabolic syndrome. After additional adjustment for moderate-to-vigorous physical activity, those in the three highest quartiles of time spent in prolonged sedentary bouts showed higher risk of metabolic syndrome compared to the lowest quartile group, with adjusted hazard ratios (95 % confidence intervals) of 2.72 (1.30 – 5.73), 2.42 (1.11 – 5.50), and 2.85 (1.31 – 6.18), respectively. No associations were seen for time spent in total and non-prolonged sedentary bouts. Sedentary behavior accumulated in a prolonged manner was associated with an increased risk of metabolic syndrome. In devising public health recommendations for the prevention of metabolic disease, the avoidance of prolonged uninterrupted periods of sedentary behavior should be considered.

Sedentary behavior has been reported to be associated with metabolic and vascular health independent of moderate-to-vigorous physical activity (MVPA). In order to select appropriate options to measure sedentary behavior in practice and research settings, it is worthwhile to characterize the extent to which objective and subjective measures of sedentary behavior quantify adverse health risks in the same population. This cross-sectional analysis compared accelerometer-derived and self-reported sedentary time to identify their association with cardio-metabolic risk factors.

The low physical activity domain of the frailty phenotype has been assessed with various self-reported questionnaires, which are prone to possible recall bias and a lack of diagnostic accuracy. The primary purpose of this study was to define the low physical activity domain of the frailty phenotype using accelerometer-based measurement and to evaluate the internal construct validity among older community-dwellers. Secondly, we examined potential correlates of frailty in this population. We conducted a cross-sectional study of 1,527 community-dwelling older men and women aged 65 and over. Data were drawn from the baseline survey of the Sasaguri Genkimon Study, a cohort study carried out in a west Japanese suburban community. Frailty phenotypes were defined by the following five components: unintentional weight loss, low grip strength, exhaustion, slow gait speed, and low physical activity. Of these criteria, physical activity was objectively measured with a tri-axial accelerometer. To confirm our measure’s internal validity, we performed a latent class analysis (LCA) to assess whether the five components could aggregate statistically into a syndrome. We examined the correlates of frailty using multiple stepwise logistic regression models. The estimated prevalence of frailty was 9.3% (95% confidence intervals, CI, 8.4-11.2); 43.9% were pre-frail (95% CI, 41.5-46.4). The percentage of low physical activity was 19.5%. Objectively-assessed physical activity and other components aggregated statistically into a syndrome. Overall, increased age, poorer self-perceived health, depressive and anxiety symptoms, not consuming alcohol, no engagement in social activities, and cognitive impairment were associated with increased odds of frailty status, independent of co-morbidities. This study confirmed the internal construct validity of the frailty phenotype that defined the low energy expenditure domain with the objective measurement of physical activity. Accelerometry may potentially standardize the measurement of low physical activity and improve the diagnostic accuracy of the frailty phenotype criteria in primary care setting. The potential role of factors associated with frailty merits further studies to explore their clinical application.