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Abstract Background Due to poorer exercise tolerance, it may be challenging for frail older adults to engage in moderate- or vigorous-intensity exercise. While low-intensity exercise interventions may be more feasible, its effectiveness for such population group remains unclear. We examined the effectiveness and implementation of community-based Baduanjin Qigong, a low-intensity exercise program in older adults with varying frailty status. Methods A two-arm, multicenter assessor-blind parallel group randomized controlled trial was conducted at three local senior activity centers. Fifty-six community-dwelling older adults with low handgrip strength were randomly allocated to either the intervention (IG) or wait-list control (CG) group. The IG underwent a supervised 16-week Baduanjin exercise program at a frequency of 2–3 × 60 min sessions/week. The CG was instructed to maintain their usual activity and received a monthly health education talk. The primary outcome measures were knee extension strength, vital exhaustion, and fear of falling. Secondary outcome measures include physiological falls risk, handgrip strength, gait speed, timed up and go test, 30-second sit-to-stand, quality of life, depression, and frailty. All outcome measures were assessed at baseline and 4-month follow-up. Results Overall, there were no statistically significant differences in all outcome measures between CG and IG at 4-month follow-up. However, in exploratory compliance analysis, a statistically significant group x time interaction was found for vital exhaustion (B = -3.65, 95% CI [-7.13, -0.16], p = .047) among participants with at least 75% attendance. In post-hoc within-group comparisons, IG showed improved vital exhaustion by 4.31 points (95% CI [1.41, 7.20], d = 0.60). The average participant attendance rate was 81.3%. No major adverse events occurred, and all participants reported positive experiences with the exercise intervention. Conclusions Our study demonstrated that Baduanjin is a safe, feasible, and acceptable exercise program that can be successfully implemented in community settings for older adults with varying frailty status. With good adherence, Baduanjin exercise could potentially be effective in alleviating vital exhaustion. However, the effectiveness of Baduanjin on physical performance, psychological measures and frailty in community-dwelling older adults remains equivocal. Trial registration ClinicalTrials.gov NCT04549103. Registered September 16, 2020.

Background: The development of an effective brief dementia test will help in the early identification of dementia. Aim: This study investigates the diagnostic utility of a brief cognitive test for dementia which combines a short subjective informant-rated questionnaire (AD8) with an objective cognitive measure (Mini-Mental State Examination, MMSE) or its subcomponents. Methods: Subjects with mild dementia (Clinical Dementia Rating Scale score ≤1) were matched with community-dwelling, cognitively intact controls. MMSE and Clinical Dementia Rating Scale were administered to all subjects, while AD8 was completed by a reliable informant. Receiver operating characteristics analysis determined the diagnostic accuracies of AD8, MMSE, and AD8 combined with MMSE (AD8+MMSE). Stepwise logistic regression identified the subcomponents of MMSE which, combined with AD8, best discriminated dementia patients from controls. Results: The AD8 (area under the curve [AUC] = 0.92, 95% confidence interval [CI] 0.89-0.95) was superior to the MMSE (AUC = 0.87, 95% CI 0.83-0.92) in discriminating mild dementia patients from controls, and AD8+MMSE (AUC = 0.95, 0.92-0.98) increased its superior discrimination over MMSE alone. AD8 combined with three-item recall and intersecting pentagon copy (AUC = 0.95, 95% CI 0.92-0.97) performed as well as AD8 combined with full MMSE. Conclusion: AD8 combined with the MMSE subcomponents three-item recall and intersecting pentagon copy has excellent diagnostic utility and is a promising brief cognitive test for early dementia.

BackgroundThymosin beta‐4 (TB4) is an X‐linked gene product with cardioprotective properties. Little is known about plasma concentration of TB4 in heart failure (HF), and its relationship with other cardiovascular biomarkers. We sought to evaluate circulating TB4 in HF patients with preserved (HFpEF) or reduced (HFrEF) ejection fraction compared to non‐HF controls. Methods and ResultsTB4 was measured using a liquid chromatography and mass spectrometry assay in age‐ and sex‐matched HFpEF (n=219), HFrEF (n=219) patients, and controls (n=219) from a prospective nationwide study. Additionally, a 92‐marker multiplex proximity extension assay was measured to identify biomarker covariates. Compared with controls, plasma TB4 was elevated in HFpEF (985 [421–1723] ng/mL versus 1401 [720–2379] ng/mL, P

Aims: To examine the association between marital status and cognitive impairment among community-dwelling Chinese older adults. Methods: We analyzed data from 2,498 Chinese aged 55 and older from the Singapore Longitudinal Aging Study cohort. Cognitive impairment was defined as a Mini-Mental State Examination total score of 23 or below. Odds ratios of associations were reported and adjusted for potential confounders in logistic regression models. Results: The prevalence of cognitive impairment was 12.2% (n = 306). Being single was associated with about 2.5 times increased odds of cognitive impairment compared to being married (adjusted OR = 2.53, 95% CI: 1.41-4.55). The association between marital status and cognitive impairment was much stronger in men compared to that in women, and was indeed statistically significant only for men. Among the single and widowed persons social engagement was associated with a lower risk of cognitive impairment. Compared with subjects in the lowest tertile of social engagement scores, the odds of having cognitive impairment was lowered by 50% for subjects in the second and the third tertile. Conclusion: Being single or widowed was associated with higher odds of cognitive impairment compared to being married in a cohort of older Chinese men but not women.

Abstract While rapid demographic changes in Asia are driving the incidence of chronic aging-related diseases, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun-metagenomic sequencing for high-resolution taxonomic and functional characterization of their gut microbiomes (n = 234). Joint species-level analysis with other Asian cohorts identified distinct age-associated shifts characterized by reduction in microbial richness, and specific Alistipes and Bacteroides species enrichment (e.g., Alistipes shahii and Bacteroides xylanisolvens). Functional analysis confirmed these changes correspond to metabolic potential expansion in aging towards alternate pathways synthesizing and utilizing amino-acid precursors, vis-à-vis dominant microbial guilds producing butyrate in gut from pyruvate (e.g., Faecalibacterium prausnitzii, Roseburia inulinivorans). Extending these observations to key clinical markers helped identify >10 robust microbial associations to inflammation, cardiometabolic and liver health, including potential probiotic species (e.g., Parabacteroides goldsteinii) and pathobionts (e.g., Klebsiella pneumoniae), highlighting the microbiome’s role as biomarkers and potential targets for promoting healthy aging.

BackgroundAdolescence is a pivotal developmental phase, marked by a high prevalence of mental health issues. The Singapore Youth Epidemiology and Resilience (YEAR) study aims to assess the prevalence of mental health symptoms, sociodemographic risk factors, and the protective role of resilience in a multi-ethnic, Asian school-going adolescent population.MethodsSchool-based adolescents aged 11-18 and their parents were invited from a stratified sample of national schools, designed to be demographically representative of the mainstream school-going population. In the screening phase, adolescents completed a battery of questionnaires including the Youth Self-Report (YSR), Child Behaviour Checklist (CBCL), and the Singapore Youth Resilience Scale (SYRESS). Thereafter, diagnostic interviews were conducted on high-risk and control participants. Data analysis was conducted to establish prevalence rates of mental health symptoms, and to examine the associations between mental health symptoms, sociodemographic factors, and resilience.ResultsThe final study sample consisted of 3336 adolescents and 2475 parents. Based on adolescents’ response on the YSR, 37.3%, 13.1% and 27.7% of the YEAR Study population scored in the clinical range for internalizing, externalizing and total problems respectively. Based on parents’ reporting on their children on the CBCL, 15.9%, 4.0% and 11.2% scored in the clinical range for internalizing, externalizing and total problems respectively. Sociodemographic risk factors for specific mental health symptoms were identified, including belonging to the age category of 15-16 (OR, 1.8-2.2) and those living in either a 4-, 5-room or executive flat (OR, 0.6-0.7), or in condominiums and other apartments (OR, 0.4-0.6). Total resilience scores were moderately correlated with total [rs(3334) = -.49, p

Objective. We aimed to examine the independent contributions of physical health and cognitive function to disability among Chinese older adults living in two Asian metropolises and explore the potential influences of environment. Design and Participants. Cross-sectional analysis based on data from two population-based studies: the Shanghai Survey of Alzheimer's Disease and Dementia (n=4639) and the Singapore Longitudinal Ageing Study (n=2397). Disability was defined as needing help in at least one activity of daily living. Results. The prevalence of functional disability was higher in Shanghai sample (5%) than that in Singapore sample (1.8%). Number of chronic diseases, self-rated health status, cognitive function (measured by the Mini-Mental State Examination), and environment (Singapore versus Shanghai) significantly contributed to functional disability independent of each other. The adjusted Odds Ratio was 1.35 (95%CI 1.22–1.50), 2.85 (95% CI 2.36–3.43), 0.89 (95% CI 0.85–0.94), and 0.68 (95% CI 0.48–0.96), respectively. The strength of associations between health variables and disability appeared to be influenced by environment. Conclusion. Physical health and cognitive function independently contributed to functional disability. The associations are modulated by environmental factors.

Abstract Objectives Higher levels of happiness are associated with longer life expectancy. Our study assessed the extent to which various factors explain the protective effect of happiness on all-cause mortality risk, and whether the association differs between older men and women. Methods Using data from the Singapore Longitudinal Aging Studies (N = 6073) of community-dwelling older adults aged ≥ 55 years, we analyzed the association of baseline Likert score of happiness (1 = very sad to 5 = very happy) and mortality from mean 11.7 years of follow up. Cox regression models were used to assess the extent to which confounding risk factors attenuated the hazard ratio of association in the whole sample and sex-stratified analyses. Results Happiness was significantly associated with lower mortality (p

Abstract INTRODUCTION White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions. METHODS We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population‐based cohorts of non‐demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains. RESULTS Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing. CONCLUSION The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.

Abstract Background Housework may provide a sustainable form of physical activity for older adults and improve health and survival outcomes. Longitudinal studies on associations between housework status over time and health outcomes are lacking. We aim to assess the longitudinal association of intensity and duration of housework with frailty and mortality outcomes. Methods Among 3270 community-dwelling prospective cohort study participants, aged ≥55 years, data on light housework (N=2996) and heavy housework (N=3022) were available at baseline (March 6, 2009, to June 11, 2013) and follow-up at 3 to 5 years later, (January 16, 2013 to August 24, 2018). Median time spent per week on light (≥420min/week) and heavy (>0min/week) household activities at baseline and follow-up were used to categorise individuals into three groups (i) consistent low levels of housework at both baseline and follow-up, (ii) inconsistent high levels of housework at either baseline or follow-up and (iii) consistent high levels of housework at both baseline and follow-up. Baseline and follow-up frailty index >0.10, and all-cause, cancer and cardiovascular mortality from mean 9.5 years follow-up to March 31, 2021. Effect estimates were adjusted for socio-demographics, nutritional risk, lifestyle and other physical activities. Results Overall, participants had mean [SD] age, 66.9 [7.8] years; 1916 [62.7%] were female. Participation in high levels of light and heavy housework consistently over time was associated with decreased odds of prefrailty/frailty at follow-up, [OR,0.61;95%CI,0.40–0.94] and [OR,0.56;95%CI,0.34–0.90] respectively, in the older group aged ≥65, compared to participants with consistent low levels of housework at baseline and follow-up. Sex-stratified analysis revealed an association between regular heavy housework participation and lower prevalence of prefrailty/frailty at follow-up in older men but not women [OR,0.31;95%CI,0.13–0.72]. Regular participation in high levels of light housework was associated with 41% lower risk of all-cause mortality [95%CI,0.36–0.96] in women but not in men, and 54% lower risk of cardiovascular mortality [95%CI,0.22–0.96]. Conclusions Regular participation in above average levels of light housework is associated with decreased odds of prefrailty/frailty in older adults aged ≥65 years, and all-cause mortality in older women. Heavy housework participation is associated with decreased odds of prefrailty/frailty, especially in older men aged ≥65. Housework may be a meaningful occupation for older adults and should be encouraged for health and wellbeing.

Abstract Background Emerging evidence suggest that in addition to low hand grip strength (HGS), HGS asymmetry is associated with declining cognitive and physical functions. We examined the associations of low HGS and asymmetry with cognitive function and functional mobility in older adults. Methods Cross-sectional data of 330 community-dwelling adults (55.2% women) aged ≥ 55 years included HGS, Repeated Battery for the Assessment of Neuropsychological Status (RBANS), and Timed-Up-and-Go (TUG). Low HGS was defined as

Asia is home to the most rapidly aging populations in the world. This study focuses on two countries in Asia that are advanced in terms of their demographic transition: the Republic of Korea and Singapore. We developed a demographic and economic state-transition microsimulation model based on the Korean Longitudinal Study of Aging and the Singapore Chinese Health Study. The model was employed to compare projections of functional status and disability among future cohorts of older adults, including disparities in disability prevalence by educational attainment. The model also projects increasing disparities in the prevalence of activities-of-daily-living disability and other chronic diseases between those with low and high educational attainment. Despite overall increases in educational attainment, all elderly, including those with a college degree, experience an increased burden of functional disability and chronic diseases because of survival to older ages. These increases have significant economic and social implications, including increased medical and long-term care expenditures, and an increased caregiver burden.

BackgroundSarcopenia is common among older individuals with and without type 2 diabetes mellitus (T2DM). There are conflicting evidence in support of the role of insulin in the development of age-related and T2DM-related sarcopenia. We investigated the relationships between the levels of fasting insulin and other blood biomarkers related to insulin or lipid metabolism with the presence of sarcopenia in two independent studies.Materials and methodsIn 246 pre-frail frail older individuals with (n = 41) and without T2DM (n = 205) in the Singapore Frailty Interventional Trial, sarcopenia was defined by low appendicular lean mass (ALM) relative to total body mass (skeletal muscle index, SMI = ALM/height2) and low lower limb strength or gait speed according to the Asian Working Group for Sarcopenia (AWGS) criteria released in 2019, and related to levels of fasting insulin and glucose, C-peptide, IGF-1, leptin, and active ghrelin. This investigation was validated in another independent study sample of 189 robust and pre-frail frail elderly in the Singapore Longitudinal Aging Study Wave 2 (SLAS-2).ResultsCompared to non-sarcopenic individuals, those with sarcopenia and possible sarcopenia showed significantly lower fasting insulin (p < 0.05) in pre-frail/frail and non-frail older individuals. Consistent trends of relationships were observed for serum levels of C-peptide, IGF-1, leptin, and active ghrelin. In multivariable logistic regression models, sarcopenia was independently associated with low insulin (p < 0.05). Levels of fasting insulin, C-peptide, and leptin were also significantly associated with BMI, SMI, knee extension strength, gait speed, and physical activity score.ConclusionDysregulated insulin secretion in diabetic and non-diabetic older individuals may play an important role in age-related and diabetes-related sarcopenia.

Abstract Background Pre‐clinical studies suggest that renin–angiotensin system blockade may improve muscle function. Clinical reports of the effect of angiotensin converting enzyme inhibitors (ACEIs) on physical functioning are inconsistent. There are no reports of the effect of angiotensin receptor blockers (ARBs) treatment in older adults. Methods We analysed data of 1268 participants in the Singapore Longitudinal Ageing Study (SLAS‐2) who provided information on the use of ACEI, ARB, and other antihypertensive drugs at baseline and follow‐up (mean 4.5 years later). Baseline and follow‐up outcome measures were cumulated deficits frailty index (CD‐FI), physical phenotype frailty index (PP‐FI), calf circumference (CC), knee extension strength, composite muscle mass and strength (MMS) z‐score, and gait speed (GS). In primary analyses, we compared the use and non‐use of an anti‐hypertensive drug class among participants with hypertensive and cardiac disease, and secondarily with participants having other chronic diseases, and those who reported no chronic diseases. Multi‐variable analyses adjusted for socioeconomic status, body mass index ≥30, ≥5 comorbidities, ≥5 drugs use, other non‐ARB or non‐ACEI drugs (calcium channel blockers, beta blockers, or hydrochlorothiazide), MMSE

Abstract Background The main aim of this study was to the determine relationship between Body Mass Index (BMI) and percentage body fat (BF%) in Singaporean adults, derive a prediction model to estimate BF%, and to report population BF%. The secondary aim was to determine the prevalence of overweight and obesity based on BF% threshold and the new risk categories for obesity in Singaporean population. Methods This was a population-based study of 542 community-dwelling Singaporeans (21–90 years old, 43.1% men). Anthropometry and body composition were assessed. Relationship between BMI and BF% were analysed using multiple regression models. Prevalence of overweight and obesity were estimated using WHO and Singapore Ministry of Health (MOH) Clinical Practice Guidelines for BMI classification, and BF% cut-off points of 25 and 35% for men and women respectively. Results We derived a prediction model to estimate BF% based on BMI, age and sex. The current cohort of Singaporeans when compared to Caucasians in the US and Europe as well as a Singapore cohort from 20 years age have higher BF% when matched for BMI, age, and sex. The overall population-adjusted prevalence of obesity according to WHO International classification (BMI ≥30 kg/m2) was 12.9% (14.9% men; 11.0% women); and 26.6% (30.7% men; 22.8% women) according to the MOH classification (BMI ≥27.5 kg/m2). However, using the BF% cut-off (> 25% for men and > 35% for women) resulted in very high prevalence of obesity of 82.0% (80.2% men; 83.8% women). Conclusion There is a large discrepancy between BF% and BMI measured obesity in Singaporean adults. The results confirmed that Singaporean adults have higher BF% at lower BMI compared to US and Europe white counterparts; and that BF% in our population has increased over two decades.

Abstract Background The rapidly aging societies worldwide and in Singapore present a unique challenge, requiring an integrated multidisciplinary approach to address high-value targets such as muscle health. We propose pragmatic evidence-based multidisciplinary consensus recommendations for the assessment and multi-modal management of muscle health in older adults (≥65 years) across the continuum of care. Methods The recommendations are derived from an in-depth review of published literature by a multidisciplinary working group with clinical experience in the care of the older population in both acute and community settings. Results The panel recommends screening for muscle impairment using the SARC-F questionnaire, followed by assessment for low muscle strength (handgrip strength or 5-times chair stand test ≥10 s as a surrogate for lower limb strength) to diagnose possible/probable sarcopenia. For uncomplicated cases, lifestyle modifications in exercise and diet can be initiated in the community setting without further assessment. Where indicated, individuals diagnosed with possible/probable sarcopenia should undergo further assessment. Diagnosis of sarcopenia should be based on low muscle strength and low muscle mass (bioimpedance analysis, dual-energy X-ray absorptiometry or calf circumference as a surrogate). The severity of sarcopenia should be determined by assessment of physical performance (gait speed or 5-times chair stand test ≥12 s as a surrogate for gait speed). To treat sarcopenia, we recommend a combination of progressive resistance-based exercise training and optimization of nutritional intake (energy, protein and functional ingredients). High quality protein in sufficient quantity, to overcome anabolic resistance in older adults, and distributed throughout the day to enable maximum muscle protein synthesis, is essential. The addition of resistance-based exercise training is synergistic in improving the sensitivity of muscle protein synthesis response to the provision of amino acids and reducing anabolic resistance. An expected dose-response relationship between the intensity of resistance-based training, lean mass and muscle strength is described. Conclusions Reviewed and endorsed by the Society of Rehabilitation Medicine Singapore and the Singapore Nutrition and Dietetics Association, these multidisciplinary consensus recommendations can provide guidance in the formulation of comprehensive and pragmatic management plans to improve muscle health in older adults in Singapore and Asia.

Abstract Background Existing research indicates that tea drinking may exert beneficiary effects on mental health. However, associations between different types of tea intake and mental health such as depression have not been fully examined. The purpose of this study was to examine the associations of green tea, fermented tea, and floral tea consumption with depressive symptoms. Methods We used data from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey, a nationwide survey on older adults in mainland China. A total of 13,115 participants (mean age 83.7 years, 54.2% were women) with valid responses were included in the analysis. The type (green, fermented [black, Oolong, white, yellow, dark, and compressed teas], and floral) and the frequency of tea consumption were recorded, and depressive symptoms were assessed using 10-item of the Center for Epidemiologic Studies Depression Scale (CES-D-10). We examined the associations between the type and the frequency of tea intake and depression, controlling for a set of demographic, socioeconomic, psychosocial, behavioral, and health-related variables. Results Overall, intakes of green tea, fermented tea, and floral tea were all significantly associated with lower prevalence of depressive symptoms, independent of other risk factors. Compared with the group of no tea intake, the adjusted ORs of depressive symptoms for daily green tea, fermented tea, and floral tea intake were 0.85 (95% CI: 0.76–0.95), 0.87 (95% CI: 0.76–0.99), and 0.70 (95% CI: 0.59–0.82), respectively. Linear associations were observed between the frequencies of all three types of tea intake and depressive symptoms (P

Abstract Background The Short Physical Performance Battery (SPPB) is an established test of physical performance. We provide reference values for SPPB and determine SPPB performance and cut-offs in assessing sarcopenia for Asian community-dwelling older adults. Methods Five hundred thirty-eight (57.8% women) community-dwelling adults aged 21–90 years were recruited. SPPB and its subtest scores and timings (8 ft. gait speed (GS), five-times repeated chair sit-to-stand (STS) and balance) were determined. Appendicular lean mass divided by height-squared, muscle strength (handgrip) and physical performance (6 m GS, STS and SPPB) were assessed to define sarcopenia for various Asian criteria. Area under the ROC curve (AUC) was used to assess performance of SPPB and subtests in discriminating sarcopenia in adults aged ≥60 years. Optimal SPPB and GS subtest cut-offs for each sarcopenia criterion were determined by maximizing sensitivity and specificity. Results The mean SPPB score was 11.6(SD 1.1) in men and 11.5(SD1.2) in women. Majority of participants(≥50%) aged 21–80 years achieved the maximum SPPB score. SPPB total and subtest scores generally decreased with age (all p

Objectives: To 1) report prevalence of ‘osteosarcopenia’ (OS) and osteosarcopenic obesity (OSO) entities using evidence-based diagnostic techniques and definitions, 2) examine if OSO offers additional predictive value of functional decline over its components, and 3) identify associated factors in a multi-racial Southeast Asian population. Methods: We performed a cross-sectional study of a representative sample of 542 community-dwelling adults (21–90 years old), and assessed anthropometry, cognition, functional performance, and self-report sociodemographic, health and lifestyle questionnaires. Low muscle mass, and the Asian Working Group for Sarcopenia (AWGS) 2019 criteria, were used to assess sarcopenia. Obesity was defined using percentage body fat and fat mass index. Osteopenia/osteoporosis was determined using lumbar spinal bone mineral density. Associated factors were examined using logistic regression, and OSO’s value investigated using linear regressions with functional performance. Results: OS and OSO prevalence were 1.8% and 0% (21–59 years), 12.9% and 2.8% (≥ 60 years), 17.3% and 4.1% (≥ 65 years), and 25.5% and 7.0% (≥75 years), respectively. OSO entity as defined was not a significant predictor (P > 0.05) and did not improve explanations for functional decline over sarcopenia or sarcopenic obesity. Age, sex, race and body mass index (BMI) were associated with OS, while age, sex, race and alcoholism were associated with OSO. Conclusions: Our results do not support OSO as a distinct entity in relation to functional decline. Aside from biological age, sex, and race, amenable lifestyle factors such as BMI and alcohol intake are important variables that can influence the co-existence of osteopenia/osteoporosis, sarcopenia and obesity.

Abstract To address the paucity of research investigating the implementation of multi-domain dementia prevention interventions, we implemented and evaluated a 24-week, bi-weekly multi-domain program for older adults at risk of cognitive impairment at neighborhood senior centres (SCs). It comprised dual-task exercises, cognitive training, and mobile application-based nutritional guidance. An RCT design informed by the Reach, Effectiveness, Adoption, Implementation, Maintenance framework was adopted. Outcome measures include cognition, quality of life, blood parameters, and physical performance. Implementation was evaluated through questionnaires administered to participants, implementers, SC managers, attendance lists, and observations. The program reached almost 50% of eligible participants, had an attrition rate of 22%, and was adopted by 8.7% of the SCs approached. It was implemented as intended; only the nutritional component was re-designed due to participants’ unfamiliarity with the mobile application. While there were no between-group differences in cognition, quality of life, and blood parameters, quality of life reduced in the control group and physical function improved in the intervention group after 24 weeks. The program was well-received by participants and SCs. Our findings show that a multi-domain program for at-risk older adults has benefits and can be implemented through neighborhood SCs. Areas of improvement are discussed. Trial registration: ClinicalTrials.gov NCT04440969 retrospectively registered on 22 June 2020.

Abstract Background Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer’s disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Methods We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence. Results The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3–24.4%) and IRT (25.6%, 95%CI = 25.1–26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1–7.0%, to 52.7%, 95%CI = 47.4–58.0%; IRT: 7.8%, 95%CI = 6.8–8.9%, to 52.7%, 95%CI = 47.4–58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades. Conclusions SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.

Metformin is an anti-diabetic drug that has shown promise to reduce M. tuberculosis susceptibility. Here the authors show that this effect is a result of metformin-mediated activation of anti-mycobacterial memory-like antigen-inexperienced CD8+CXCR3+ T cells, an effect that also boosts response to BCG vaccination.

Aging is associated with immune attrition that may impact the effectiveness of the immune system to protect the host from pathogens. Here the authors show that immune aging is associated with alterations in the Wnt/β-catenin signaling and reduced stem cell memory T lymphocytes, hinting the Wnt/β-catenin pathway as a potential therapy target.

Background Prospective cohort studies suggest that frailty is associated with an increased risk of incident cardiovascular disease (CVD) morbidity and mortality, but their mechanistic and developmental relations are not fully understood. We investigated whether frailty predicted an increased risk of incident nonfatal and fatal CVD among community-dwelling older adults. Methods A population cohort of 5015 participants aged 55 years and above free of CVD at baseline was followed for up to 10 years. Pre-frailty and frailty were defined as the presence of 1–2 and 3–5 modified Fried criteria (unintentional weight loss, weakness, slow gait speed, exhaustion, and low physical activity), incident CVD events as newly diagnosed registered cases of myocardial infarction (MI), stroke, and CVD-related mortality (ICD 9: 390 to 459 or ICD-10: I00 to I99). Covariate measures included traditional cardio-metabolic and vascular risk factors, medication therapies, Geriatric Depression Scale (GDS), Mini-Mental State Exam (MMSE), and blood biomarkers (haemoglobin, albumin, white blood cell counts and creatinine). Results Pre-frailty and frailty were significantly associated with elevated HR = 1.26 (95%CI: 1.02–1.56) and HR = 1.54 (95%CI:1.00–2.35) of overall CVD, adjusted for cardio-metabolic and vascular risk factors and medication therapies, but not after adjustment for GDS depression and MMSE cognitive impairment. The HR of association between frailty status and both CVD mortality and overall mortality, however, remained significantly elevated after full adjustment for depression, cognitive and blood biomarkers. Conclusion Frailty was associated with increased risk of CVD morbidity and especially mortality, mediated in parts by traditional cardio-metabolic and vascular risk factors, and co-morbid depression and associated cognitive impairment and chronic inflammation. Given that pre-frailty and frailty are reversible by multi-domain lifestyle and health interventions, there is potential benefits in reducing cardiovascular diseases burden and mortality from interventions targeting pre-frailty and early frailty population.

Objectives Regular moderate-to-vigorous intensity recreational physical activity (PA) improves physical and cognitive functions. However, the age-associated relationships between non-recreational PA and functional ability remain less explored. We examined the associations between housework and functional health among younger and older Singaporean community-dwelling adults.Design Cross-sectional study.Setting and participants Younger (

Background: Multi-system physiological dysregulation (PD) may represent a biological endo-phenotype of clinical frailty. We investigated the co-occurrence of PD with physical frailty and its contributions to the known impact of frailty on adverse health outcomes.Methods: Data of 2,725 participants from the Singapore Longitudinal Aging Studies (SLAS-2), included baseline measures of physical frailty and PD derived from Mahalanobis distance (Dm) value of 23 blood biomarkers. We analyzed their concurrent association and their impacts on 9-year mortality, MMSE cognition, GDS depression, number of medications, disability, and hospitalization at baseline and follow up (mean 4.5 years).Results: Global PD (Log10Dm, mean = 1.24, SD = 0.24) was significantly but weakly associated with pre-frailty-and-frailty. Controlling for age, sex and education, pre-frailty-and-frailty (HR = 2.12, 95% CI = 1.51–3.00) and PD (HR = 3.88, 95% CI = 2.15–6.98) predicted mortality. Together in the same model, mortality HR associated with pre-frailty-and-frailty (HR = 1.83, 95% CI = 1.22–2.73) and PD (HR = 3.06, 95% CI = 1.60–5.85) were reduced after additionally adding global PD to the prediction model. The predictive accuracy for mortality were both approximately the same (PD: AUC = 0.62, frailty: AUC = 0.64), but AUC was significantly increased to 0.68 when combined (p < 0.001). Taken into account in the same model, frailty remained significantly associated with all health and functional outcomes, and PD was significantly associated with only MMSE, disability and medications used. In secondary analyses, there were mixed associations of system-specific PDs with frailty and different adverse outcomes.Conclusions: Co-existing PD and physical frailty independently predict mortality and functional and health outcomes, with increased predictive accuracy when combined. PD appears to be a valid representation of a biological endo-phenotype of frailty, and the potential utility of such subclinical measures of frailty could be further studied.

Background: This cross-sectional study aimed to identify and compare the contributions of physiological and cognitive performance to variations in gait characteristics in middle-aged (41-60 years), older-aged (61-70 years) and oldest-aged adults (>70 years). Methods: A total of 385 community-dwelling, well-functioning adults, aged 41-90 years, were randomly recruited into the study. The participants were divided into three age groups: middle-aged, older-aged and oldest-aged adults. Demographic data, height, weight, education level and information on comorbidities were recorded. Cognition was measured using the Repeatable Battery for the Assessment of Neuropsychological Status. Physiological performance included visual contrast sensitivity (VCS), postural sway, gait analysis, hand reaction time, handgrip strength (HGS) and knee extensor strength (KES). Multivariable regression tests were used to examine the association between physiological and cognitive performance with gait characteristics in age-stratified analyses. Results: HGS contributed significantly to gait variances in the middle-aged adults. KES and attention were the main determinants of gait speed and phase domain of gait for the older-aged adults. In the oldest-aged adults, HGS (ẞ=-0.32, p

Summary: The elderly are an important target for influenza vaccination, and the determination of factors that underlie immune responsiveness is clinically valuable. We evaluated the immune and metabolic profiles of 205 elderly Singaporeans administered with Vaxigrip. Despite high seroprotection rates, we observed heterogeneity in the response. We stratified the cohort into complete (CR) or incomplete responders (IR), where IR exhibited signs of accelerated T cell aging. We found a higher upregulation of genes associated with the B-cell endoplasmic-reticulum stress response in CR, where XBP-1 acts as a key upstream regulator. B-cells from IR were incapable of matching the level of XBP-1 upregulation observed in CR after inducing ER stress with tunicamycin in vitro. Metabolic signatures also distinguished CR and IR – as CR presented with a greater diversity of bile acids. Our findings suggest that the ER-stress pathway activation could improve influenza vaccination in the elderly.

Abstract Background Few empirical studies support a bio-psycho-social conceptualization of frailty. In addition to physical frailty (PF), we explored mental (MF) and social (SF) frailty and studied the associations between multidimensional frailty and various adverse health outcomes. Methods Cross-sectional and longitudinal analyses were conducted using data from a population-based cohort (SLAS-1) of 2387 community-dwelling Singaporean Chinese older adults. Outcomes examined were functional and severe disability, nursing home referral and mortality. PF was defined by shrinking, weakness, slowness, exhaustion and physical inactivity, 1–2 = pre-frail, 3–5 = frail; MF was defined by ≥1 of cognitive impairment, low mood and poor self-reported health; SF was defined by ≥2 of living alone, no education, no confidant, infrequent social contact or help, infrequent social activities, financial difficulty and living in low-end public housing. Results The prevalence of any frailty dimension was 63.0%, dominated by PF (26.2%) and multidimensional frailty (24.2%); 7.0% had all three frailty dimensions. With a few exceptions, frailty dimensions share similar associations with many socio-demographic, lifestyle, health and behavioral factors. Each frailty dimension varied in showing independent associations with functional (Odds Ratios [ORs] = 1.3–1.8) and severe disability prevalence at baseline (ORs = 2.2–7.3), incident functional disability (ORs = 1.1–1.5), nursing home referral (ORs = 1.5–3.4) and mortality (Hazard Ratios = 1.3–1.5) after adjusting for age, gender, medical comorbidity and the two other frailty dimensions. The addition of MF and SF to PF incrementally increased risk estimates by more than 2 folds. Conclusions This study highlights the relevance and utility of PF, MF and SF individually and together. Multidimensional frailty can better inform policies and promote the use of targeted multi-domain interventions tailored to older adults’ frailty statuses.

BackgroundSarcopenia and obesity are reportedly associated with risk of cognitive decline, and sarcopenic obesity (SO) heightens the risk, but the evidence is sparse and inconclusive. This study aimed to examine the association between SO and cognitive impairment.MethodsA total of 542 community-dwelling adults aged between 21 and 90 years were recruited. All participants were assessed for body composition (dual X-ray absorptiometry), handgrip strength (HGS), gait speed (GS), and cognitive function (Repeatable Battery for the Assessment of Neuropsychological Status). Sarcopenia was defined by the presence of low appendicular lean mass index (ALMI) and low HGS or low GS according to the 2019 Asian Working Group for Sarcopenia criteria, and obesity was defined based on the upper two quintiles of fat mass index (FMI).ResultsSarcopenia alone or in combination with obesity were not significantly associated with cognitive impairment after controlling for confounding variables. Obesity on its own was significantly associated with greater odds of impaired attention (OR: 2.05, 95%CI 1.12-3.82). Low ALMI was not associated, but low HGS, slow GS, and high FMI were individually associated with cognitive impairment: low HGS and immediate memory (OR: 1.91, 95% CI 1.04-3.49); low GS and immediate memory (OR: 2.17, 95% CI 1.26-3.72); high FMI and attention (OR: 2.06, 95% CI 1.22-3.51). Co-occurring high FMI with either low HGS or slow GS exacerbated the observed odds of global and domain-specific (attention, visuospatial) cognitive impairment.ConclusionsLean mass is not relevant, whereas muscle strength and physical performance or adiposity are relevant in defining sarcopenia or sarcopenic obesity in terms of their cognitive impacts.

Abstract Introduction Mild cognitive impairment (MCI) is characterized by subtle deficits that functional assessment via informant‐report measures may not detect. Sensors can potentially detect deficits in everyday functioning in MCI. This study aims to establish feasibility and acceptability of using sensors in a smart home for performance‐based assessments of two instrumental activities of daily living (IADLs). Methods Thirty‐five older adults (>65 years) performed two IADL tasks in a smart home laboratory equipped with sensors and a web camera. Participants’ cognitive states were determined using published criteria including measures of global cognition and comprehensive neuropsychological test batteries. Selected subtasks of the IADL assessment were autonomously captured by the sensors. Total time taken for each task and subtask were computed. A point scoring system captured accuracy and number of attempts. Acceptability of the smart home setup was assessed. Results Participants with MCI (n = 21) took longer to complete both tasks than participants with healthy cognition (HC; n = 14), with significant time differences observed only in "Cost calculation." Completion time for IADL tasks and scores correlated in the expected direction with global cognition. Over 95% of the participants found the smart home assessment acceptable and a positive experience. Discussion We demonstrated the feasibility and acceptability of the use of unobtrusive commercially available sensors in a smart home for facilitating parts of the objective assessment of IADL in older adults. Future studies need to identify more IADLs that are suitable for semi‐automated or automated assessments through the use of simple, low‐cost sensors.

BackgroundWith no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups.Methods and findingsWe harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife.ConclusionsThese results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

We describe a network-based method to obtain a subset of representative variables from clinical data of subjects of the second Singapore Longitudinal Aging Study (SLAS-2), while preserving to a good extent the predictive performance of the full set with regards to a multi-faceted index of successful aging, SAGE. To examine differences in predictive performance of high-degree nodes ("hubs") and high-centrality ones ("cores"), we implement four subsetting strategies (two degree-based, two centrality-based) and obtain four surrogate sets of variables, which we use as input features for machine learning models to predict the SAGE index of subjects. All four models have variables belonging to the physical, cardiovascular, cognitive and immunological domains among their fifteen most important predictors. A fifth domain (leisure-time activities, LTA) is also present in some form. From a comparison of the surrogate sets' size and predictive performance, a centrality-based approach (selection of the most central variable-nodes within each cluster) yielded the smallest-sized surrogate set, while having high prediction accuracy (measured by its model's area-under-curve, AUC) in comparison to its analogous degree-based strategy (selection of the highest-degree nodes per cluster). Inclusion of the next most-central variables yielded negligible changes in predictive performance while more than doubling the surrogate set size. The centrality-based approach thus yields a surrogate set which offers a good balance between number of variables and prediction performance, and can act as a representative subset of the SLAS-2 clinical dataset.

BackgroundThe 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.Methods and findingsWe 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.ConclusionsCognitive 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.