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Shan Hai,1 Qi Gao,2 Xinyi Gwee,2 Denise Qian Ling Chua,2 Keng Bee Yap,3 Tze Pin Ng2 1Gerontology and Geriatrics Centre, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 3Department of Medicine, Ng Teng Fong General Hospital, SingaporeCorrespondence: Tze Pin NgDepartment of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Level 9, NUHS Tower Block, 1E Kent Ridge Road, 119228, SingaporeTel +65 6772 4518; +65 6772 3478Fax +65 6777 2191Email pcmngtp@nus.edu.sgPurpose: Malnutrition and population ageing are doubly global healthcare challenges. It is widely recognized that disability is a major contributor to malnutrition among older people, but the importance of reducing malnutrition risk (MR) for disability prevention is given little attention. We investigated the association between MR and risk of incident disability and functional decline among community-dwelling older persons.Materials and Methods: Prospective cohort study of community-dwelling older adults aged 55 and above (Singapore Longitudinal Ageing Study) with 3– 5 years follow-up. MR was measured at baseline using an appropriate and validated index (ENIGMA); physical and functional measures at baseline and follow-up included instrumental and basic activity of daily living (ADL), knee extension (KES), gait velocity (GV), timed up-and-go (TUG).Results: Compared to low MR, mild-moderate MR (OR = 1.43, 95% CI = 1.02– 2.01) and severe MR (OR=1.74, 95% CI=1.10– 2.74) were associated with higher risks of incident disability. Severe MR was associated with functional decline (OR = 1.69, 95% CI = 1.11– 2.57). Estimates were adjusted for demographic, social, lifestyle behaviour and health variables. In particular, eating difficulty was associated with incident disability and functional decline, and low lymphocyte with functional decline. Severe MR and low albumin were associated with 37% worse GV and 126% worse TUG declines; consuming few vegetables or fruits with 34% worse KES decline; polypharmacy with 56% worse TUG decline.Conclusion: Malnutrition risk increased the risk of incident disability and functional decline in non-disabled persons, it worsened physical performance declines. Further studies should investigate the effectiveness of nutritional interventions in reducing the risk of disability among older people.Keywords: malnutrition, functionality, ageing, prospective cohort study

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 Conclusions Among Chinese older adults, regularly consumed any type of tea (green, fermented, or floral) were less likely to show depressive symptoms, the associations seemed more pronounced among floral tea and green tea drinkers.

Few studies have comprehensively described changes in blood biomarkers of the physiological responses underlying sarcopenia reduction associated with lifestyle interventions. In this study, we performed secondary analyses of data in a randomized controlled trial of multi-domain lifestyle interventions (6-month duration physical exercise, nutritional enrichment, cognitive training, combination and standard care control) among 246 community-dwelling pre-frail and frail elderly, aged ≥65 years, with and without sarcopenia. Appendicular lean mass (ALM), lower limb strength, gait speed, and blood levels of markers of muscle metabolism, inflammation, anti-oxidation, anabolic hormone regulation, insulin signaling, tissue oxygenation were measured at baseline, 3-month and 6-month post-intervention. Multi-domain interventions were associated with significant (p < 0.001) reduction of sarcopenia at 3-month and 6-month post-intervention, improved gait speed, enhanced lower limb strength, and were equally evident among sarcopenic participants who were slower at baseline than non-sarcopenic participants. Active intervention was associated with significantly reduced inflammation levels. Sarcopenia status and reduction were associated with blood biomarkers related to muscle metabolism, steroid hormone regulation, insulin-leptin signaling, and tissue oxygenation. Physical, nutritional and cognitive intervention was associated with measures of sarcopenia reduction, together with changes in circulating biomarkers of anabolic and catabolic metabolism underlying sarcopenia.

Translation of community-based functional training for older adults to reduce frailty is still lacking. We evaluated the effectiveness and implementation of a community-delivered group-based functional power training (FPT) program for frail older adults within their neighborhoods. A two-arm, multicenter assessor-blind stratified randomized controlled trial was conducted at four local senior activity centers in Singapore. Sixty-one community-dwelling older adults with low handgrip strength were randomized to intervention (IG) or control (CG) group. The IG underwent the FPT program (power and balance exercises using simple equipment) delivered by a community service provider. The 12-week program comprised 2 × 60 min sessions/week. CG continued usual activities at the centers. Functional performance, muscle strength, and frailty status were assessed at baseline and 3 months. Program implementation was evaluated using RE-AIM framework. The program was halted due to Coronavirus Disease 2019-related suspension of senior center activities. Results are reported from four centers, which completed the program. IG showed significantly greater improvement in the Short Physical Performance Battery test as compared to CG (p = 0.047). No effects were found for timed up and go test performance, muscle strength, and frailty status. The community program exhibited good reach, effectiveness, adoption, and implementation. Our study demonstrated that FPT was associated with greater improvement in physical function in pre-frail/frail participants as compared to exercise activities offered at local senior activity centers. It is a feasible intervention that can be successfully implemented for frail older adults in their neighborhoods. Trial registration ClinicalTrials.gov, NCT04438876. Registered 19 June 2020–retrospectively registered.

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.

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

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.

Background: Mild cognitive impairment (MCI) is a critical pre-dementia target for preventive interventions. There are few brief screening tools based on self-reported personal lifestyle and health-related information for predicting MCI that have been validated for their generalizability and utility in primary care and community settings. Objective: To develop and validate a MCI risk prediction index, and evaluate its field application in a pilot community intervention trial project. Design: Two independent population-based cohorts in the Singapore Longitudinal Ageing Study (SLAS). We used SLAS1 as a development cohort to construct the risk assessment instrument, and SLA2 as a validation cohort to verify its generalizability. Setting: community-based screening and lifestyle intervention Participants: (1) SLAS1 cognitively normal (CN) aged ≥55 years with average 3 years (N=1601); (2) SLAS2 cohort (N=3051) with average 4 years of follow up. (3) 437 participants in a pilot community intervention project. Measurements: The risk index indicators included age, female sex, years of schooling, hearing loss, depression, life satisfaction, number of cardio-metabolic risk factors (wide waist circumference, pre-diabetes or diabetes, hypertension, dyslipidemia). Weighted summed scores predicted probabilities of MCI or dementia. A self-administered questionnaire field version of the risk index was deployed in the pilot community project and evaluated using pre-intervention baseline cognitive function of participants. Results: Risk scores were associated with increasing probabilities of progression to MCI-or-dementia in the development cohort (AUC=0.73) and with increased prevalence and incidence of MCI-or-dementia in the validation cohort (AUC=0.74). The field questionnaire risk index identified high risk individuals with strong correlation with RBANS cognitive scores in the community program (p

Experimental evidence suggest that tea polyphenols have anti-depressant effect and tea consumption may reduce the risk and severity of depression. We investigated whether tea consumption was associated with changes in depressive symptoms over time among Asian older adults. Population-based prospective cohort study with mean 4 years of follow up. Singapore Longitudinal Ageing Study (SLAS) of community-living older persons. 3177 participants overall (mean age 67 years) and 3004 participants who were depression-free at baseline. Baseline tea consumption which include Chinese (black, oolong or green) tea or Western (mixed with milk) tea and change in Geriatric Depression Scale (GDS) measure of depression. Incident depression was defined by GDS≥5, and GDS depression improvement or deterioration by GDS change of ≥4 points. Estimated odds ratio and 95% confidence intervals (OR, 95%CI) were adjusted for baseline age, sex, ethnicity, education, housing type, single/divorced/widowed, living alone, physical and social activity, smoking, alcohol, number of comorbidities, MMSE, and baseline GDS level. Compared to non-tea drinkers, participants who consumed ≥3 cups of tea of all kinds were significantly less likely to have worsened GDS symptoms: OR=0.32, 95% CI=0.12, 0.84. Among baseline depression-free participants, the risk of incident GDS (≥5) depression was significantly lower (OR=0.34, 95%CI=0.13, 0.90) for daily consumption of all types of tea, and Chinese (black, oolong or green) tea (OR=0.46, 95%CI=0.21,0.99). This study suggests that tea may prevent the worsening of existing depressive symptoms and the reduce the likelihood of developing threshold depression.

Background While there have been studies in Singapore on the prevalence and economic burden of osteoporotic hip fracture, there is a severe lack of reference data on bone mineral density and prevalence of osteoporosis. The purpose of this study is to establish the reference values for BMD and compare prevalence of osteoporotic conditions using other available reference values so as to better understand the status of bone health in Singaporean adults. Methods We carried out a population-based cross-sectional study using dual-energy x-ray absorptiometry (Hologic Discovery Wi) to measure the bone mineral density of Singaporean adults aged ≥21 years. A total of 542 participants were recruited from the large north-eastern residential town of Yishun. We computed T- scores (denoted by TSG) for each individual in the study. Similar diagnoses were also done based on T-scores provided by the densitometer (TDXA), NHANES database (TNHANES), and China (TCHN), and the differences in prevalence compared. We then compared the concordance between TSG and TDXA in the classification of osteoporosis. Osteoporosis was defined according to criteria by the World Health Organization (WHO). Results Peak lumbar spine BMD was 1.093 ± 0.168 g/cm2 in women, and 1.041 ± 0.098 g/cm2 for men. Peak whole-body BMD was 1.193 ± 0.93 g/cm2 in women at, and 1.224 ± 0.112 g/cm2 for men. Prevalence of osteoporosis based on lumbar spine was 9.3% in postmenopausal women, and 0.7% in men after 50 years of age. The percentage difference in prevalence range from 60.5–163.6%, when using reference values from TDXA, TNHANES, and TCHN. Comparing diagnosis using TDXA and TSG cut-off values, 28 versus 15 women were diagnosed as osteoporotic respectively. The kappa statistics was 0.81 for women and 0.85 for men. Conclusion: Our study shows that T-scores provided by DXA manufacturer over-diagnosed osteoporosis in Singaporeans, and the prevalence of osteoporotic conditions is not accurately represented. This over-diagnosis may result in unnecessary treatment in some individuals.

Background Age-related slowing of gait has been reported to start as early as the fifth decade and accelerate beyond the seventh decade of life. A single cut-off for slow gait may not be appropriate for men and women of different ages. We aimed to report reference values for gait speed and spatiotemporal gait parameters of adult age groups in a South East Asian population. Methods A total of 507 community-dwelling adults, aged 21-90 years were recruited into the study through random sampling, filling quotas of 20-40 participants in each sex and age group (10-year age groups between 21 and 60 years; 5-year age groups beyond age 60 years). Demographic data, height, weight and information on comorbidities were recorded. Habitual gait speed and spatiotemporal parameters were measured, and the average of three trials was recorded using the GAITRite system. Results Gait speed peaked in their 40s for both men and women, but the trajectories differed slightly across age groups. Although similar for men in their 50s and 60s, gait speed was significantly slower among those aged 71 years and older. For women beyond 50 years old, gait slowed with age. After adjusting for height, women were found to walk significantly faster and with a longer step length than men. Women also walked with a significantly narrower stride width and less external rotation of the feet. The lowest quintile for gait speed in our study cohort was 0.9m/s, below the recommended cut-off of 1.0m/s. Conclusion We established the reference values as well as the quintiles for gait speed and spatiotemporal gait parameters across adult age groups in a multi-ethnic Asian population. This contributes to a valuable database for gait assessment and evaluation of preventive or rehabilitative programs.

We aim to examine body composition, and association between SO and cognitive performance in Type 2 Diabetes (T2D) in an Asian population in Singapore.This was a cross-sectional study on 1235 patients with mean age 61.4 ± 8.0 years and T2D primary and secondary care attending diabetes care in Singapore. Body composition was assessed using tetrapolar multi-frequency BIA device analysis. Fat mass to fat-free mass (FM/FFM) ratio was categorized into 3 groups: Group 1, normal,0.40; Group 2, obese and increase of FM is small relative to that in FFM, 0.40 to 0.80; and Group 3, SO,0.80. Cognition was assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Mini-Mental State Examination (MMSE).The distribution of body composition based on FM/FFM ratio was: Group 1, 20.2%; Group 2, 60.5%; and Group 3, 19.4%. SO (Group 3) was significantly associated with reduced RBANS total score with β-1.44 (95%CI -2.82 to -0.06; p = 0.041) in multivariable linear regression adjusted for demographics, education, depressive symptom(s) and clinical covariates. SO was significantly associated with reduced index scores for immediate memory and language in fully adjusted models with corresponding βs -2.71 (95%CI -5.06 to -0.36; p = 0.024) and -2.48 (95%CI -4.87 to -0.08; p = 0.043). Association between SO and reduced MMSE score was similarly observed.The prevalence of SO in Asians with T2D is relatively high. There is consistent and independent association of SO with reduced cognitive performance, especially in domains of memory and language, which may impair complex executive function such as adherence to diabetes self-care management.

Introduction: The identification of modifiable health span-promoting factors is a public health priority. Objective: To explore the socio-environmental, lifestyle, behavioural, and psychological determinants of a clinical phenotypic measure of biological ageing in the Singapore Longitudinal Ageing Study (SLAS) cohort. Methods: Using cross-sectional data on 2,844 SLAS-2 adults with a chronological age (CA) ≥55 years, we estimated biological age (BA) using a validated panel of clinical, biochemical, physiological, and functional indicators (8 in men and 10 in women) and calculated the difference between BA and CA (BA – CA in years). Potential determinants included education, housing status, loss of a spouse, living alone, lifestyle and health activity, smoking, alcohol consumption, nutritional risks, consumption of milk, soy, fruit, vegetables, coffee and tea, sleep parameters, and life satisfaction. Results: The mean CA was 67.0 (standard deviation [SD] 7.9; range 55–94) years. The estimated BA varied more widely (SD 8.9 years; range 47.5–119.9 years), and BA – CA ranged from –11.3 to 30.0 years. In stepwise selection regression analyses, multiple significant independent determinants in a final model were larger for private housing, being single/divorced/widowed, productivity, cognitive and leisure time activity scores, 10 h/week of moderate-to-vigorous physical activity, unintended loss of weight, life satisfaction, and daily consumption of fruits 1–2 or ≥3 servings and Chinese tea 1–2 or ≥3 cups daily, together explaining 16% of BA – CA variance in men and 14% in women. Associated BA – CA estimates were highest in men with high-end housing status (–1.8 years, effect size 0.015) and unintended weight loss (1.5 years, effect size 0.017). Conclusion: We identified determinants of biological ageing which can promote health span.

ObjectivesRegular 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.DesignCross-sectional study.Setting and participantsYounger (Outcome measuresPhysical function was assessed using Short Physical Performance Battery (SPPB), repeated-chair-sit-to-stand and gait speed. Cognitive and sensorimotor functions were assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Physiological Profile Assessment (PPA), respectively.MethodsLight housework (LH) and heavy housework (HH), recreational, and occupational and transport-related PAs were assessed using PA questionnaires. Participants were dichotomised into low-volume and high-volume LH and HH groups. Results were adjusted for level of recreational and other non-recreational PAs.ResultsAmong older but not younger adults, RBANS scores were 8% and 5% higher in high HH and LH groups compared with low HH and LH groups, respectively (p=0.012 and p=0.016). Specifically, HH was associated with 14% higher attention score (p=0.014), and LH was associated with 12% and 8% higher immediate and delayed memory scores, respectively (pConclusionsAmong older adults, housework is associated with higher cognitive function, specifically in attention and memory. Associations of housework with physical function and sensorimotor performance were intensity dependent. Housework PA is positively associated with functional health among community-dwelling older adults, independent of recreation and other non-recreational PAs. Further longitudinal and intervention studies are needed to establish causality.

We previously developed a malnutrition risk index, the Elderly Nutritional Index for Geriatric Malnutrition Assessment (ENIGMA) with good predictive accuracy for mortality risk in an original population cohort (SLAS1). Herein, we further evaluate the concurrent and predictive validity of the ENIGMA construct in an external validation cohort (SLAS-2) of 2824 community-dwelling older adults aged 55+ years. They were assessed on the ENIGMA index, Mini Nutritional Assessment-Short Form (MNA-SF) and the Geriatric Nutritional Risk Index (GNRI), known correlates of malnutrition, and baseline and follow-up functional dependency and 10-year mortality risk. Higher ENIGMA risk categories were significantly associated (P < 0·001) with lower education, living alone, smoking, low physical activity, BMI < 18·5 kg/m2, poorer muscle strength and functional mobility, exhaustion, physical frailty, homocysteine, glomerular filtration rate, Hb, red and white blood cell counts, platelets, systemic inflammation indexes, metabolic syndrome, CVD, cognitive impairment and depressive symptoms (Geriatric Depression Scale ≥ 5). ENIGMA scores showed statistically significant (P < 0·001) correlations but low-to-moderate concordance with MNA-SF (r = 0·148, agreement = 45·9 %, kappa = 0·085) and GNRI scores (r = 0·156, agreement = 45·8 %, kappa = 0·096). Controlling for known correlates of malnutrition, only high-risk ENIGMA among the indexes significantly predicted baseline functional dependency (OR = 1·64, 95 % CI 1·01, 2·65) and mortality (hazard ratio = 1·65 (95 % CI 1·04, 2·62). ENIGMA marginally out-performed MNA-SF and GNRI in predicting baseline functional dependency (AUC: 0·625 v. 0·584 v. 0·526), follow-up functional dependency (AUC: 0·594 v. 0·525 v. 0·479) and 10-year mortality risk (AUC: 0·641 v. 0·596 v. 0·595). The concurrent and predictive validity of the ENIGMA construct is replicated in an external evaluation study of community-dwelling older persons.

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., Graphical abstract, Highlights • Seroprotected elderly had heterogeneous titre responses to all three influenza strains • Multi-strain responses are linked to distinct transcriptomic and bile acid profiles • XBP-1 related pathways are specifically enriched in complete responders • XBP-1 upregulation is better preserved in vaccinated complete responders, Immunology; Virology; Clinical microbiology; Cell biology

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

Objectives Older adults who are malnourished are at high risk for adverse functional and mortality outcomes. The aim of this study was to assess the long-term changes in nutritional status among community-living older adults and their associations with adverse health outcomes. Methods This was a population-based observational cohort study (Singapore Longitudinal Aging Study, SLAS 1), with a 4- to 5-y follow-up of 2075 community-living adults ≥60 y of age. Nutritional status (Mini Nutritional Assessment Short-Form [MNA-SF] and Nutritional Screening Initiative [NSI]), instrumental/basic activities of daily living (IADLs/ADLs) and quality of life (QoL) were assessed at both baseline and at the 4- to 5-y follow-up. The 10-y mortality was assessed from the date of 4- to 5-y follow-up to March 2017. Estimates of associations between changes in nutritional status and adverse health outcomes were analyzed using multinomial logistic regression or Cox proportional hazards regression, and indicated by odds ratios/hazard ratios (ORs/HRs) and 95% confidence intervals (CIs). Results Nutritional status was dynamic from baseline to the 4- to 5-y follow-up according to both MNA-SF and NSI. Compared with persistent normal nutrition, nutritional deterioration was associated with increased incident IADL/ADL disability (MNA-SF: OR, 3.22; 95% CI, 1.13–9.16), poor QoL (MNA-SF: OR, 4.53; 95% CI 2.13–9.64), and mortality (MNA-SF: HR, 4.76; 95% CI, 2.82–8.03; NSI: HR, 1.99; 95% CI, 1.27–3.14); nutritional improvement was associated with decreased incident IADL/ADL disability (NSI: OR, 0.17; 95% CI, 0.05–0.59); persistent poor nutrition (MNA-SF at risk/malnourished or NSI moderate/high nutritional risk) was associated with elevated incidence of poor QoL (MNA-SF: OR, 1.92,; 95% CI, 1.05–3.52; NSI: OR, 2.31; 95% CI, 1.19–4.49) and mortality (MNA-SF: HR, 2.57; 95% CI, 1.59–4.15; NSI: HR 1.97; 95% CI, 1.17–3.32). Compared with persistent poor nutrition, nutritional improvement was also associated with decreased incidence of mortality (MNA-SF: HR, 0.43; 95% CI, 0.23–0.80). Conclusions Changes in nutritional status are associated with adverse health outcomes, and should be monitored with simple screening tools to identify older adults at high risk for adverse functional and mortality outcomes for selective nutritional interventions.

Background Biological age (BA) is a more accurate measure of the rate of human aging than chronological age (CA). However, there is limited consensus regarding measures of BA in life span and healthspan. Methods This study investigated measurement sets of 68 physiological biomarkers using data from 2,844 Chinese Singaporeans in two age subgroups (55–70 and 71–94 years) in the Singapore Longitudinal Aging Study (SLAS-2) with 8-year follow-up frailty and mortality data. We computed BA estimate using three commonly used algorithms: Principal Component Analysis (PCA), Multiple Linear Regression (MLR), and Klemera and Doubal (KD) method, and additionally, explored the use of machine learning methods for prediction of mortality and frailty. The most optimal algorithmic estimate of BA compared to CA was evaluated for their associations with risk factors and health outcome. Results Stepwise selection procedures resulted in the final selection of 8 biomarkers in males and 10 biomarkers in females. The highest-ranking biomarkers were estimated glomerular filtration rate for both genders, and the forced expiratory volume in 1 second in males and females. The BA estimates robustly predicted frailty and mortality and outperformed CA. The best performing KD measure of BA was notably predictive in the younger group (aged 55–70 years). BA estimates obtained using a machine learning train-test method were not more accurate than conventional BA estimates in predicting mortality and frailty in most situations. Biologically older people with the same CA as biologically younger individuals had higher prevalence of frailty and 8-year mortality, and worse health, behavioral, and functional characteristics. Conclusions BA is better than CA for measuring life span (mortality) and healthspan (frailty). This measurement set of physiological markers of biological aging among Chinese robustly differentiate biologically old from younger individuals with the same CA.

Background Clinicians need improved tools to better identify nonacute heart failure with preserved ejection fraction (HFpEF). Objectives The purpose of this study was to derive and validate circulating microRNA signatures for nonacute heart failure (HF). Methods Discovery and validation cohorts (N = 1,710), comprised 903 HF and 807 non-HF patients from Singapore and New Zealand (NZ). MicroRNA biomarker panel discovery in a Singapore cohort (n = 546) was independently validated in a second Singapore cohort (Validation 1; n = 448) and a NZ cohort (Validation 2; n = 716). Results In discovery, an 8-microRNA panel identified HF with an area under the curve (AUC) 0.96, specificity 0.88, and accuracy 0.89. Corresponding metrics were 0.88, 0.66, and 0.77 in Validation 1, and 0.87, 0.58, and 0.74 in Validation 2. Combining microRNA panels with N-terminal pro–B-type natriuretic peptide (NT-proBNP) clearly improved specificity and accuracy from AUC 0.96, specificity 0.91, and accuracy 0.90 for NT-proBNP alone to corresponding metrics of 0.99, 0.99, and 0.93 in the discovery and 0.97, 0.96, and 0.93 in Validation 1. The 8-microRNA discovery panel distinguished HFpEF from HF with reduced ejection fraction with AUC 0.81, specificity 0.66, and accuracy 0.72. Corresponding metrics were 0.65, 0.41, and 0.56 in Validation 1 and 0.65, 0.41, and 0.62 in Validation 2. For phenotype categorization, combined markers achieved AUC 0.87, specificity 0.75, and accuracy 0.77 in the discovery with corresponding metrics of 0.74, 0.59, and 0.67 in Validation 1 and 0.72, 0.52, and 0.68 in Validation 2, as compared with NT-proBNP alone of AUC 0.71, specificity 0.46, and accuracy 0.62 in the discovery; with corresponding metrics of 0.72, 0.44, and 0.57 in Validation 1 and 0.69, 0.48, and 0.66 in Validation 2. Accordingly, false negative (FN) (81% Singapore and all NZ FN cases were HFpEF) as classified by a guideline-endorsed NT-proBNP ruleout threshold, were correctly reclassified by the 8-microRNA panel in the majority (72% and 88% of FN in Singapore and NZ, respectively) of cases. Conclusions Multi-microRNA panels in combination with NT-proBNP are highly discriminatory and improved specificity and accuracy in identifying nonacute HF. These findings suggest potential utility in the identification of nonacute HF, where clinical assessment, imaging, and NT-proBNP may not be definitive, especially in HFpEF.

Frailty is associated with future cardiovascular events in older adults. This cross-sectional study examined the relationship between subclinical vasculopathy with measures of skeletal muscle mass and function. Asymptomatic community-dwelling Asians ≥55 years underwent assessments for subclinical vasculopathy (carotid intima-media thickness (cIMT), aortic and carotid stiffness, and endothelial function), muscle mass (calf circumference adjusted for body mass index) and function (knee extension strength, 6-meter fast gait speed). Multivariable regression analyses for associates of muscle mass/function controlled for demographics and cardiometabolic risk factors. Among 336 participants (median age 62 years, 55.1% male, 3.6% sarcopenia), cIMT, aortic and carotid stiffness inversely correlated with muscle mass, strength and gait speed; cIMT remained independently associated with gait speed (β=-0.26) in multivariable analyses. Age and sex significantly modified the relationship between subclinical vasculopathy and muscle mass/function. Associations, only found in those aged ≥70, included cIMT with gait speed (β=-0.48) and knee strength (β=-9.33), and aortic augmentation index and aortic stiffness composite z-score with gait speed (β=-0.11 and β=-0.19 respectively). Among males, cIMT correlated with gait speed (β=-0.31). The association of subclinical vasculopathy with skeletal muscle mass and function in asymptomatic adults ≥55 years is best reflected by cIMT. The roles of mediating pathways deserve further evaluation.

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.

Studies suggest that nutritional interventions using the whole diet approach such as the Mediterranean diet may delay cognitive decline and dementia onset. However, substantial numbers of older adults are non-adherent to any ideally healthy dietary pattern and are at risk of malnutrition. The present study investigated the relationship between global malnutrition risk and onsets of cognitive decline and neurocognitive disorders (NCD), including mild cognitive impairment (MCI) or dementia in community-dwelling older adults. Participants aged ≥55 years in the Singapore Longitudinal Ageing Studies (SLAS) were assessed at baseline using the Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA) and followed up 3–5 years subsequently on cognitive decline (MMSE drop ≥ 2) among 3128 dementia-free individuals, and incident neurocognitive disorders (NCD) among 2640 cognitive normal individuals. Individuals at high nutritional risk score (≥3) were more likely to develop cognitive decline (OR=1.42, 95%CI=1.01–1.99) and incident MCI-or-dementia (OR=1.64, 95%CI=1.03–2.59), controlling for age, sex, ethnicity, low education, APOE-e4, hearing loss, physical, social, and mental activities, depressive symptoms, smoking, alcohol, central obesity, hypertension, diabetes, low HDL, high triglyceride, cardiac disease, and stroke. Among ENIGMA component indicators, low albumin at baseline was associated with cognitive decline and incident NCD, and 5 or more drugs used, few fruits/vegetables/milk products daily, and low total cholesterol were associated with incident NCD. The ENIGMA measure of global malnutrition risk predicts cognitive decline and incident neurocognitive disorders, suggesting the feasibility of identifying vulnerable subpopulations of older adults for correction of malnutrition risk to prevent neurocognitive disorders.

Introduction: Many studies on hearing loss (HL) and cognition are limited by subjective hearing assessments and verbally administered cognition tests, the majority of the document findings in Western populations. This study aimed to assess the association of HL with cognitive impairment among ethnic Chinese Singaporean older adults using visually presented cognitive tests. Methods: The hearing of community-dwelling older adults was assessed using pure tone audiometry. Cognitive function was assessed using the Computerized Cambridge Cognitive Test Battery (CANTAB). Multiple regression analyses examined the association between hearing and cognitive function, adjusted for age, education, and gender. Results: HL (pure-tone average [PTA] of thresholds at 0.5, 1, 2, and 4 kHz in the better ear, BE4PTA) was associated with reduced performance in delayed matching and multitasking tasks (β = −0.25, p = 0.019, and β = 0.02, p = 0.023, respectively). Moderate to severe HL was associated with reduced performance in delayed matching and verbal recall memory tasks (β = −10.6, p = 0.019, and β = −0.28, p = 0.042). High-frequency HL was associated with reduced performance in the spatial working memory task (β = 0.004, p = 0.022). All-frequency HL was associated with reduced performance in spatial working memory and multitasking (β = 0.01, p = 0.040, and β = 0.02, p = 0.048). Conclusion: Similar to Western populations, HL among tonal language-speaking ethnic Chinese was associated with worse performance in tasks requiring working memory and executive function.

Background Cognitive training can improve cognition in healthy older adults. Objective The objectives are to evaluate the implementation of community-based computerized cognitive training (CCT) and its effectiveness on cognition, gait, and balance in healthy older adults. Methods A single-blind randomized controlled trial with baseline and follow-up assessments was conducted at two community centers in Singapore. Healthy community-dwelling adults aged 55 years and older participated in a 10-week CCT program with 2-hour instructor-led group classes twice a week. Participants used a mobile app to play games targeting attention, memory, decision making, visuospatial abilities, and cognitive flexibility. Implementation was assessed at the participant, provider, and community level (eg, reach, implementation, and facilitators and barriers). Effectiveness measures were the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Color Trails Test 2 (CTT-2), Berg Balance Scale, and GAITRite walkway measures (single and dual task gait speed, dual task cost, and single and dual task gait variability index [GVI]). Results A total of 94 healthy community-dwelling adults participated in the CCT program (mean age 68.8 [SD 6.3] years). Implementation measures revealed high reach (125/155, 80.6%) and moderate adherence but poor penetration of sedentary older adults (43/125, 34.4%). The effectiveness data were based on intention-to-treat (ITT) and per-protocol (PP) analysis. In the ITT analysis, single task GVI increased (b=2.32, P=.02, 95% CI [0.30 to 4.35]) and RBANS list recognition subtest deteriorated (b=–0.57, P=.01, 95% CI [–1.00 to –0.14]) in both groups. In the PP analysis, time taken to complete CTT-2 (b=–13.5, P=.01, 95% CI [–23.95 to –3.14]; Cohen d effect size = 0.285) was faster in the intervention group. Single task gait speed was not statistically significantly maintained in the intervention group (b=5.38, P=.06, 95% CI [–0.30 to 11.36]) and declined in the control group (Cohen d effect size = 0.414). PP analyses also showed interaction terms for RBANS list recall subtest (b=–0.36, P=.08, 95% CI [–0.75 to 0.04]) and visuospatial domain (b=0.46, P=.08, 95% CI [–0.05 to 0.96]) that were not statistically significant. Conclusions CCT can be implemented in community settings to improve attention and executive function among healthy older adults. Findings help to identify suitable healthy aging programs that can be implemented on a larger scale within communities. Trial Registration ClinicalTrials.gov NCT04439591; https://clinicaltrials.gov/ct2/show/NCT04439591

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 Conclusions Population-specific normative SPPB values are important for use in diagnostic criteria and to interpret results of studies evaluating and establishing appropriate treatment goals. Performance on the SPPB should be reported in terms of the total sum score and registered time to complete the repeated-chair STS and 8-ft walk tests. The performance of GS subtest was comparable to SPPB and could be a useful, simple and accessible screening tool for discriminating severe sarcopenia in community-dwelling older adults.

To determine the overlapping prevalence of malnutrition and sarcopenia and the association between parameters of malnutrition with muscle mass and strength in a community-dwelling Singaporean adult population. This was a cross-sectional study. Large north-eastern residential town of Yishun in Singapore. Random sampling of community-dwelling Singaporeans aged 21–90 years old (n=541). Anthropometry, body composition and handgrip strength (muscle strength) were measured. Sarcopenia was identified using dual-energy x-ray absorptiometry scan (muscle mass). Nutritional status was measured using Mini Nutritional Assessment (MNA-SF). Other questionnaires collected included physical activity and cognition. Associations between nutritional status with sarcopenia as well as with muscle mass and strength were analysed using multinomial logistics and linear regressions. The overall population-adjusted prevalence of those at nutritional risk and malnourished were 18.5% and 0.1% respectively. More than a third of participants (35%) who were at nutritional risk were sarcopenic. Malnourished participants were all sarcopenic (100%, N=2) whereas those who were sarcopenic, 27.0% (N=37) were at nutritional risk/malnourished. Being at nutritional risk/malnourished was significantly associated with 2 to 3 times increased odds of sarcopenia in multivariate analyses adjusting for age, gender, physical activity level and cognition, and fat mass index. Favourable MNA parameter scores on food intake and BMI were positively associated with greater muscle mass and handgrip strength (p

Background Studies investigating the association between depression and aortic stiffness in older patients with type 2 diabetes are lacking. We postulated an association between depressive symptoms and aortic stiffness, and this relationship may be mediated by increased adiposity. Methods We analyzed participants with type 2 diabetes aged 55 years or older (n = 958). We measured aortic stiffness using carotid–femoral pulse wave velocity (cut-off ≥ 12 m/s) using the tonometry method. We defined depressive symptoms as a score of greater than 5 on the Geriatric Depression Scale–15 (GDS-15). Adiposity indices we assessed were body mass index, waist circumference, waist-to-height ratio, visceral fat area and fat mass. Results Among the participants, 27.2% had aortic stiffness, of whom 6.5% had depressive symptoms. Score on the GDS-15 was correlated with pulse wave velocity, and both variables were correlated with the adiposity markers we analyzed (all p < 0.05). Depressive symptoms were associated with pulse wave velocity (B = 1.79, 95% confidence interval [CI] 0.83–2.75) or aortic stiffness (risk ratio 1.60, 95% CI 1.10–2.33) in the unadjusted model. The association persisted after controlling for demographics, duration of diabetes, glycated hemoglobin, comorbidities and medications. Further adjustment for visceral fat area and fat mass in separate models reduced the association between depressive symptoms and pulse wave velocity or aortic stiffness. Mediation models revealed that the mediation proportions of fat mass and visceral fat area on the association between depressive symptoms and pulse wave velocity were 11.8% and 9.7%, respectively. A preliminary analysis of longitudinal data (n = 184) showed similar findings. Limitations Causality cannot be inferred from the associations we observed. Conclusion Depressive symptoms are associated with elevated pulse wave velocity in older people with type 2 diabetes, and this relationship may be partially mediated by increased adiposity.

Background Consideration of circulating biomarkers for risk stratification in heart failure (HF) is recommended, but the influence of atrial fibrillation (AF) on prognostic performance of many markers is unclear. We investigated the influence of AF on the prognostic performance of circulating biomarkers in HF. Methods N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide, C-type natriuretic peptide (CNP), NT-proCNP, high-sensitivity troponin-T, high-sensitivity troponin-I, mid-regional-propeptide adrenomedullin, co-peptin, growth differentiation factor-15, soluble Suppressor of Tumorigenicitiy (sST2), galectin-3, and procalcitonin plasma concentrations were measured in a prospective, multicenter study of adults with HF. AF was defined as a previous history of AF, and/or presence of AF/flutter on baseline 12-lead electrocardiogram. The primary outcome was the composite of HF-hospitalization or all-cause mortality at 2 years. Results Among 1099 patients (age 62 ± 12years, 28% female), 261(24%) patients had AF. Above-median concentrations of all biomarkers were independently associated with increased risk of the primary outcome. Significant interactions with AF were detected for galectin-3 and sST2. In considering NT-proBNP for additive risk stratification, sST2 (adjusted hazard ratio [AHR]1.85, 95%confidence interval [C.I.] 1.17-2.91) and galectin-3 (AHR1.85, 95%C.I. 1.09-2.45) were independently associated with increased primary outcome only in the presence of AF. The prognostic performance of sST2 was also stronger in AF for all-cause mortality (AF: AHR2.82, 95%C.I. 1.26-6.21; non-AF: AHR1.78, 95% C.I. 1.14-2.76 without AF), while galectin-3 predicted HF-hospitalization only in AF (AHR1.64, 95%C.I. 1.03-2.62). Conclusions AF modified the prognostic utility of selected guideline-endorsed HF-biomarkers. Application of markers for prognostic purposes in HF requires consideration of the presence or absence of AF. Clinical trial registration ACTRN12610000374066

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.

Background: Regular moderate-to-vigorous intensity recreational physical activity (PA) protects against ill health. The relationship between non-recreational PA with ageing health is less explored, especially in high income countries. We examined the associations between housework and functional health among younger and older Singaporean community-dwelling adults. Methods: Younger (

International audience; 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.

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.

Background Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. Results Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10–1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38–6.47) and Latin America (OR = 1.49, 95% CI = 1.04–2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33–3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81–26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07–3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44–8.35) in Asia. Conclusion Parity is associated with women’s risk of dementia, though this is not uniform across regions and dementia subtypes.

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54–103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

Patients with type 2 diabetes (T2D) have a lower risk of Mycobacterium tuberculosis infection, progression from infection to tuberculosis (TB) disease, TB morality and TB recurrence, when being treated with metformin. However, a detailed mechanistic understanding of these protective effects is lacking. Here, we use mass cytometry to show that metformin treatment expands a population of memory-like antigen-inexperienced CD8+CXCR3+ T cells in naive mice, and in healthy individuals and patients with T2D. Metformin-educated CD8+ T cells have increased (i) mitochondrial mass, oxidative phosphorylation, and fatty acid oxidation; (ii) survival capacity; and (iii) anti-mycobacterial properties. CD8+ T cells from Cxcr3−/− mice do not exhibit this metformin-mediated metabolic programming. In BCG-vaccinated mice and guinea pigs, metformin enhances immunogenicity and protective efficacy against M. tuberculosis challenge. Collectively, these results demonstrate an important function of CD8+ T cells in metformin-derived host metabolic-fitness towards M. tuberculosis infection., 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.

Objectives The “timed up and go” (TUG) test is a simple and widely used test of overall functional mobility. There is a paucity of TUG normative data among Asian individuals who differ in habitual gait speed and fall risk from Western population. The objectives of this study were to determine TUG reference values and optimum cutoffs predicting prevalent and incident disability for community-dwelling adults. Design One cross-sectional (Study 1–Yishun Study) and one longitudinal (Study 2–Singapore Longitudinal Aging Study) study in Singapore. Setting and Participants Study 1 comprised 538 nondisabled, community-dwelling adults aged between 21 and 90 years. Study 2 comprised 1356 community-dwelling older adults aged ≥55 years followed for 3 years. Methods Study 1 collected TUG reference values and assessed physiological fall risk (PFR) using the Physiological Profile Assessment (PPA). Study 2 assessed association of TUG with disability with the Barthel Index and the Lawton scale at baseline and follow-up. Results From Study 1, mean TUG time for individuals aged 60 to 74 years was 9.80 seconds, shorter than values reported for Westerners of 12.30 seconds. It was significantly associated with high PFR [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.03–1.27], 74.0% agreement, Cohen's kappa = 0.314 (95% CI 0.238–0.390); area under the curve = 0.85 (95% CI 0.80–0.90). A TUG cutoff of 10.2 seconds discriminated high PFR from low PFR with 84.4% sensitivity and 72.6% specificity. In Study 2, the threshold for observing significantly increased risk of disability was ≥9.45 seconds for prevalent disability (OR 2.98, 95% CI 1.41–6.78), functional decline (OR 2.68, 95% CI 1.33–5.80), and incidental disability (OR 2.25, 95% CI 1.08–4.97). Conclusions and Implications TUG reference values and cutoff predicting disability for community-dwelling older adults in Singapore are consistent with Asian data and lower than for Western individuals. TUG could be used to guide development and evaluation of risk screening of adverse health outcomes across the life span in Singapore.

Background: Studies indicate that physiological and cognitive aging are causally related and functionally interdependent. However, the relative contribution of physiological factors and cognition to dual-task costs (DTC) of gait parameters has not been well studied. In this cross-sectional study, we examined the trajectory of DTC of gait parameters across the adult age spectrum for both sexes and identified the contributions of physical and cognitive performance to DTC of gait. Methods: A total of 492 community-dwelling adults, aged 21–90 years, were randomly recruited into the study. Participants were divided into 7 age groups, with 10-year age range for each group. Demographic data, height, body mass, education level, and information on comorbidities were recorded. Cognition was measured using the Repeatable Battery for the Assessment of Neuropsychological Status. Physical performance included visual contrast sensitivity, postural sway, hand reaction time, handgrip strength, knee extensor strength, and single-task and dual-task gait assessments. Stepwise multivariable regression was used to examine the association between physical and cognitive performance with DTC of gait parameters. Results: Women were found to have significantly higher DTC of gait speed (p = 0.01), cadence (p < 0.01), and double support time (p < 0.01) than men. However, significant aging effect on DTC of gait speed (p = 0.01), step length (p = 0.01), and double support time (p = 0.01) was observed in men but not in women. Immediate memory was the primary determinant for the DTC of gait speed (β = −0.25, p < 0.01), step length (β = −0.22, p < 0.01), and cadence (β = −0.15, p = 0.03) in men. Besides immediate memory, postural sway (β = −0.13, p = 0.03) and hand reaction (β = 0.14, p = 0.02) were also significantly associated with DTC of step length and cadence, respectively, in women. Conclusion: There were sex differences in the amplitude and trajectories of DTC of gait parameters. The DTC increased with age in men but not in women. Immediate memory was the primary determinant of DTC of gait parameters in men while immediate memory, postural sway, and reaction time were associated with DTC of gait in women. Future studies should investigate the clinical implications of the sex differences in the DTC with fall risks.

Diabetic patients taking metformin have lower risk for Mycobacterium tuberculosis (Mtb) infection, progression from infection to tuberculosis (TB) disease, TB morality and TB recurrence. However, a detailed mechanistic understanding of metformin’s protective immunological benefits on host resistance to TB is lacking. In this study, using mass cytometry we show that metformin treatment expands memory-like antigen-inexperienced CD8+CXCR3+ T cells in naïve mice, and in healthy and diabetic humans. Metformin-educated CD8+ T cells have increased (i) mitochondrial mass, oxidative phosphorylation, and fatty acid oxidation; (ii) survival capacity; and (iii) anti-mycobacterial properties. CD8+ T cells from CXCR3−/− mice did not exhibit metformin-mediated metabolic programming. In BCG-vaccinated mice and guinea pigs, metformin enhanced immunogenicity and protective efficacy against Mtb challenge. Collectively, our results demonstrate an important role of CD8+ T cells in metformin-derived host metabolic-fitness towards Mtb infection.

Tze Pin Ng,1 Qi Gao,1 Xinyi Gwee,1 Denise QL Chua,1 Wan C Tan2 1Gerontology Research Programme, Department of Psychological Medicine, National University of Singapore, Singapore; 2Centre for Heart Lung Innovation, Department of Medicine, University of British Columbia, Vancouver, BC, CanadaCorrespondence: Tze Pin NgGerontology Research Programme, Department of Psychological Medicine, National University of Singapore, NUHS Tower Block, 9 th Floor, 1E Kent Ridge Road, 119228, SingaporeTel +65-67723478Fax +65-67772191 Email pcmngtp@nus.edu.sgObjective: The anti-oxidant and anti-inflammatory actions of phytochemicals and the smooth muscle relaxant actions of theophylline present in tea may confer pulmonary protection and reduce COPD risk. We investigated tea consumption (black, oolong, or green) association with COPD risks in a population-based cohort study of older adults aged ≥ 55.Methods: GOLD criteria was used to identify prevalent and incident cases of COPD (FEV1/FVC < 0.70) among 4617 participants and 920 participants free of COPD at baseline who were assessed at follow-up 4.5 years later.Results: Prevalent cases of COPD consumed less tea than their non-COPD counterparts. Estimated odds ratio (OR) and 95% confidence intervals (95% CI) of association with prevalent COPD, adjusted for age, sex, ethnicity, housing type, smoking, alcohol, physical activity and BMI declined across tea consumption levels (p-trend=0.048), and was lowest for ≥ 3 cups/day (OR=0.77, 95% CI=0.61– 0.96). The cumulated incidence of COPD declined across tea consumption categories (p-trend=0.012) and the lowest OR of association (OR=0.35, 95% CI=0.17– 0.69) with consuming ≥ 3 cups/day after co-variate adjustment.Conclusion: Different kinds of tea showed similar non-significant trends of associations but appeared to be strongest for green tea. Tea consumption in this Asian population was associated with lowered COPD prevalence and incidence.Keywords: phytochemical, polyphenols, theophylline, epidemiological, longitudinal

Background Frailty is a common geriatric syndrome, characterized by reduced physiologic reserve and increased vulnerability to stressors, due to cumulative decline in multiple physiological systems. We studied the feasibility of a community-delivered Baduanjin (BDJ) training program among pre-frail/frail community-dwelling older people. We examined (1) safety (adverse events) and physical and psychological effects; and (2) feasibility of recruitment, retention, adherence; recruitment efforts, and any program challenges, so as to inform future studies. Methods Our study was a single arm pre-post study in a community setting. Sixteen-week group BDJ training (2×/week in the first 4 weeks and 3×/week thereafter) was co-designed and implemented by community-based providers in Singapore. Recruitment, attendance, and adverse events were recorded throughout the training. A participants’ survey was also administered after the training program. Effects of the intervention on physical and functional outcomes (hand grip strength, knee extension strength, Time Up and Go (TUG), Physiological Profile Assessment (PPA), 30-s Sit-to-Stand test, 6-m fast gait speed test), frailty outcomes (frailty score and status), and other outcomes (Maastricht Questionnaire (MQ), Fall Efficacy Scale (FES), Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS), and EQ-5D-5L) were examined before and after the program. Results Of 31 older adults screened to be frail, 15 met inclusion criteria and 3 refused participation, resulting in 12 older adults (9 women) enrolled into the program. During the program, one participant was hospitalized (unrelated to BDJ training) and the other 11 (aged 77 ± 6 years; 2 frail, 9 prefrail at baseline) completed the program with average overall attendance of 89%. Most (89%) of the 44 training sessions had attendance > 80%. The program received positive feedback with no training-related adverse events. Participants either reversed (n = 2) or maintained (n = 9) their frailty statuses. There post-training outcomes in hand grip strength, knee extension strength, TUG, MQ, FES, MoCA, GDS, and EQ-5D-5L index score appeared to be better. The reduction of frailty and PPA fall risk scores was of moderate-to-large effect size. Conclusions Community-delivered BDJ training program was safe and feasible for prefrail/frail older adults with the potential to improve physical and cognitive function, reduce fall risk, improve psychological well-being, and reverse frailty status.

Background There are inconsistent evidence for the association between fish consumption and dementia risk, and emerging evidence suggesting that dairy consumption is associated with lower dementia risk, based on a limited number of prospective cohort studies. Methods We investigated the association of dairy and fish consumption with the risk of developing mild cognitive impairment (MCI) and dementia. High intake of daily consumption of milk and dairy products and consumption of fish at least three servings per week were determined at baseline for 1,164 community-living and cognitively normal Chinese individuals aged 55 + in the Singapore Longitudinal Ageing Study (SLAS-1), who were followed-up (average 3.5 years) for incident cases of MCI and dementia determined by established criteria. Results The participants’ mean (SD) age was 65.1 (6.9) years, 66.8% were female. Controlling for sex, age, low or no education, APOE-e4 status, physical, social and productive activity, depression (GDS ≥ 5), central obesity, prediabetes/diabetes, hypertension, abnormal lipids, cardiac diseases, and daily fruit/vegetable intake in multivariable analysis, daily intake of milk and dairy products was significantly associated with lower risk of incident MCI (OR = 0.61; 95% CI = 0.39–0.96) or MCI-dementia (OR = 0.62; 95% CI = 0.40–0.95). Fish intake was not significantly associated with lowered risk of incident MCI and MCI-dementia, (OR = 0.74, 95%CI = 0.49–1.13 for MCI; OR = 0.76, 95% CI = 0.51–1.14 for MCI-dementia). Conclusions High dairy intake was associated with approximately 40% reduced risk of MCI or dementia. There is weak support in this study of an association between fish intake and MCI-dementia risk. Trial Registration: ClinicalTrials.gov NCT03405675. Registered 23 January 2018 (retrospectively registered).