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Introduction: Gait variability is associated with frailty, dementia, and falls. Studies on the association of physiological and cognitive factors with gait variability have seldom included middle-aged adults, even though these adults already experienced loss of muscular strength and postural stability. This study aimed a) to examine and compare the trend of gait variability in men and women, across the adult age spectrum, and b) to identify and compare the contributions of physiological and cognitive factors to gait variability. Methods: This was a population-based cross-sectional study at a single center. A random sample of 507 community-dwelling, well-functioning adults aged 21–90 years were studied. Cognition was measured using the Repeatable Battery for the Assessment of Neuropsychological Status. Physiological factors examined included visual contrast sensitivity (VCS), postural sway, hand reaction time, handgrip strength (HGS), knee extensor strength, and gait variability (coefficient of variation [CoV]). Multivariable regression models were used to examine the association between physiological and cognitive performance with gait CoV. Results: Women walked with greater stride width CoV (p < 0.01) and double support time (DST) CoV (p < 0.01) than men. The stride width (p = 0.01) and DST variability (p = 0.03) were significantly higher in older men as compared to men in younger age-groups. Gait speed accounted for most of the gait CoV variances and attenuated the effects of physiological performance and/or attention cognition on most gait variability, except for CoV of DST and stride width. Adults with better VCS (β = −0.19), faster hand reaction (β = 0.12), and greater HGS (β = −0.15) had lower variability in step length. Conclusion: The trends of stride width CoV and DST CoV across adult age spectrum were different between men and women. Greater stride width variability was partly attributed to greater HGS, possibly to better control lateral stability during walking. Physiological factors outweigh cognition in regulating most of the gait CoV in this study. They are modifiable and potential targets for healthy aging program.

The association of malnutrition with chronic kidney disease (CKD) is well established. However, there is a paucity of studies of the effect of malnutrition risk (MR) on kidney function decline among older persons who do not have end-stage or dialyzable CKD. This study aimed to examine the association between MR status and kidney function, and future risks of kidney function decline and CKD progression in community-dwelling older adults.Nutrition Screening Initiative's DETERMINE Your Nutritional Health Checklist and estimated glomerular filtration rate (eGFR) were assessed at baseline among 5,122 participants free of end-stage renal failure or dialyzed CKD in the Singapore Longitudinal Aging Studies (SLAS-1 and SLAS-2). Follow-up eGFR was assessed in a subcohort of SLAS-2 participants without CKD (eGFR60 mL/min/1.73 mIn baseline cross-sectional analyses adjusting for other risk factors, low, moderate, and high MR was significantly associated with decreasing eGFR coefficients of -1.5, -3.3, and -5.0 mL/min/1.73 mAmong older adults without advanced kidney disease, MR is associated with poor kidney function and increased risk of kidney function decline and CKD. Preventive interventions to modify MR may help to reduce the deterioration of renal function in older people.

Background: The association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) use and cognitive function in type 2 diabetes remains unclear. Objective: Explore the association between SGLT2i and longitudinal changes in cognitive function in adults with type 2 diabetes (T2DM) and assessed the cognitive domains which were impacted by SGLT2i. Methods: We conducted a prospective cohort study of 476 patients aged 60.6±7.4 years with follow-up period up to 6.4 years. Data on SGLT2i use was derived from questionnaire and verified with clinical database. We used Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess cognition. The association between SGLT2i use and rate of RBANS score change was examined using multiple linear regression. Results: There were 138 patients (29.0%) on SGLT2i, including 84 (17.7%) for

Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear.We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults.Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week).This cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.

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.

Introduction: There is empirical evidence that cardiovascular risk factors and vascular pathology contribute to cognitive impairment and dementia. Methods: We profiled cardiometabolic and vascular disease (CMVD) and CMVD burden in community-living older adults in the Singapore Longitudinal Ageing Study cohort and examined the association of CMVD risk markers with the prevalence and incidence of mild cognitive impairment (MCI) and dementia from a median 3.8 years of follow-up. Results: Prevalent MCI and dementia, compared with normal cognition, was associated with higher proportions of persons with any CMVD, hypertension, diabetes, coronary heart disease, atrial fibrillation, or stroke. Diabetes, stroke, and the number of CMVD risk markers remained significantly associated with dementia or MCI after adjusting for age, sex, formal education level, APOE-ε4 genotype, and level of physical, social, or productive activities, with odds ratios ranging from 1.3 to 5.7. Among cognitively normal participants who were followed up, any CMVD risk factor, dyslipidemia, diabetes, or heart failure at baseline predicted incident MCI or its progression to dementia after adjusting for potential confounders. Conclusion: Older adults with higher burden of CMVD, driven especially by diabetes, are likely to increase the risk of prevalent and incident MCI and dementia.

Objectives This study establishes age- and sex-specific reference values for fat mass index (FMI), lean mass index (LMI), appendicular LMI (aLMI), and body fat distribution indices including Android/Gynoid % fat ratio and Trunk/Limb % fat ratio in multi-ethnic Singaporean adults. Methods A population-based cross-sectional study using dual-energy X-ray absorptiometry (Hologic Discovery Wi) was carried out to measure whole body and regional fat and lean mass in community-dwelling adults. A total of 537 adults (57.5% women), aged from 21 to 90 years, were recruited from the large north-eastern residential town of Yishun. Age- and sex-specific percentile reference values were generated for FMI, LMI, aLMI, Android/Gynoid % fat ratio and Trunk/Limb % fat ratio using the Lambda–Mu–Sigma method. The relationship between the parameters and age were assessed through the Pearson’s correlation coefficient. Results All parameters demonstrated significant correlation with age (p < 0.05) for both men and women, except for LMI in women, with the strength of r ranging from 0.12 (weak correlation) to 0.54 (strong correlation). LMI (r = −0.45) and appendicular LMI (r = −0.54) were negatively associated with age in men while none (r = −0.06) to weak correlation (r = −0.14) were shown in women for the same parameters respectively. The Android/Gynoid % fat ratio and Trunk/Limb % fat ratio were positively related to age for both men (r = 0.37 & 0.43, p < 0.001) and women (r = 0.52 & 0.48, p < 0.001). Conclusion We have established DXA-based body composition reference data for the Singapore adult population. These reference data will be particularly useful in geriatric, obesity and oncology clinics, enabling the prescription of appropriate therapy to individuals at risk of morbidity from unfavorable body composition phenotypes. It also adds on to the limited reference database on Southeast Asian body composition.

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 Motor and gait disturbances are evident in early Alzheimer and non-Alzheimer dementias and may predict the likelihood of mild cognitive impairment (MCI) or progression to dementia. Objective We investigated the Timed-Up-and-Go (TUG) measure of functional mobility in predicting cognitive decline and incident MCI or early dementia (MCI–dementia). Design Prospective cohort study with 4.5 years follow-up. Setting Population based. Participants 2,544 community-dwelling older adults aged 55+ years. Methods Participants with baseline data on TUG, fast gait speed (GS), knee extension strength (KES) and performance-oriented mobility assessment (POMA) gait and balance were followed up for cognitive decline (Mini-Mental State Exam; MMSE drop of ≥2, among 1,336 dementia-free participants) and incident MCI–dementia (among 1,208 cognitively normal participants). Odds ratio (OR) and 95% confidence intervals (95% CI) were adjusted for age, sex, education, smoking, physical, social and productive activity, multi-morbidity, metabolic syndrome and MMSE. Results Per standard deviation increase in TUG, POMA, GS and KES were significantly associated with incident MCI–dementia: TUG (OR = 2.84, 95% CI = 2.02–3.99), GS (OR = 2.17, 95% CI = 1.62–2.91), POMA (OR = 1.88, 95% CI = 1.22–2.92) and KES (OR = 1.52, 95% CI = 1.15–2.02). Adjusted OR remained significant only for TUG (OR = 1.52, 95% CI = 1.01–2.31) and GS (OR = 1.53, 95% CI = 1.08–2.16). Areas under the curve (AUC) for TUG (AUC = 0.729, 95% CI = 0.671–0.787) were significantly greater than GS (AUC = 0.683, 95% CI = 0.619–0.746), KES (AUC = 0.624, 95% CI = 0.558–0.689) and POMA (AUC = 0.561, 95% CI = 0.485–0.637). Similar associations with cognitive decline were significant though less pronounced, and adjusted ORs remained significant for TUG, GS and POMA. Conclusion Functional mobility decline precedes incident MCI and early dementia. The TUG appears to be especially accurate in predicting the future risks of adverse cognitive outcomes. Trial Registration ClinicalTrials.gov NCT03405675. Registered 23 January 2018 (retrospectively registered).

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 Results Low HGS, but not asymmetry, was independently associated with lower functional mobility performance (β = 1.3, 95%CI = 0.6,1.9), global cognitive function (β = -10.4, 95%CI = -17.0,-3.8), immediate (β = -2.6, 95%CI = -4.5,-0.7) and delayed (β = -2.8, 95%CI = -5.0,-0.7) memory. Compared to normal and symmetric HGS participants, low HGS in combination with HGS asymmetry was associated with poorer language scores. In participants with normal HGS, asymmetric HGS was associated with slower TUG than corresponding groups with symmetric HGS. Conclusion Low HGS, but not asymmetry, was associated with lower cognition and functional mobility. Associations of combined low HGS and asymmetry with cognitive and physical functions were driven by grip strength rather than asymmetry.

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.

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

Older people’s participation in activities is critical to their health and well-being. Active lifestyle in old age reduces the risk of mortality, prevents chronic diseases, promotes physical and mental wellbeing, and is conducive to active and healthy aging. While various measures of participation have been proposed, a holistic measure that includes both social and individual activity participation is currently unavailable. To enable lifestyle medicine recommendations, we developed the Older People’s Activity Participation (OPAP) scale to understand the constituent factors of older people’s everyday activities. This study examined OPAP’s internal consistency using Cronbach’s alpha, convergent validity using regression analysis, as well as factor structure using exploratory and confirmatory factor analyses in a dense urban setting. Preliminary items assessed engagement in 27 health-related, fitness, recreational, social, productive, and cognitive activities, and were administered to 270 community-dwelling adults aged 50 and older in Singapore. The 17-item OPAP showed acceptable internal consistency (Cronbach’s alpha= .69), and demonstrated convergence with a validated measure of social cohesion (B=.27, p

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.

Background: Type 2 diabetes mellitus (T2DM) has been shown to increase the risks of cognitive decline and dementia. Paired box gene 4 (PAX4), a transcription factor for beta cell development and function, has recently been implicated in pathways intersecting Alzheimer’s disease and T2DM. Objective: In this report, we evaluated the association of the ethnic-specific PAX4 R192H variant, a T2DM risk factor for East Asians which contributes to earlier diabetes onset, and cognitive function of Chinese T2DM patients. Methods: 590 Chinese patients aged 45–86 from the SMART2D study were genotyped for PAX4 R192H variation using Illumina OmniExpress-24 Array. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) which had been validated in the Singapore population was administered to assess five cognitive domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Multiple linear regression was used to assess the association of the R192H risk allele and cognitive domains. Results: Patients with two PAX4 R192H risk alleles showed significantly lower attention index score (β= –8.46, 95% CI [–13.71, –3.21], p = 0.002) than patients with wild-type alleles after adjusting for age, gender, diabetes onset age, HbA1c, body-mass index, renal function, lipid profiles, systolic blood pressure, metformin usage, smoking history, education level, Geriatric Depression Scale score, and presence of APOE ɛ4 allele. Conclusion: Ethnic-specific R192H variation in PAX4 is associated with attention-specific cognitive impairment in Chinese with T2DM. Pending further validation studies, determining PAX4 R192H genotype may be helpful for early risk assessment of early-onset T2DM and cognitive impairment to improve diabetes care.

Type 2 diabetes mellitus (T2DM) has been shown to be associated with cognitive decline and dementia. As earlier onset of diabetes implies a longer disease duration and an increased risk to complications, we sought to investigate the effect of T2DM onset on cognitive function of our patients.We administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to T2DM patients aged 45-85 from our SMART2D cohort. We assessed the association of the T2DM onset age (both continuous and stratified into 3 groups: early-onset ≤40 (n = 326), middle-aged onset 41-64 (n = 703) and late-onset ≥65 years old (n = 38)) and RBANS cognitive indices in 1067 patients. Potential mediation of this association by vascular compliance using mediation analysis was investigated.T2DM onset associates significantly with RBANS total score. Patients with early T2DM onset have lower RBANS total score as compared to patients with middle-aged onset (β = -2.01, p = 0.0102) and those with late-onset (β = -5.80, p = 0.005). This association was partially mediated by pulse pressure index (25.8%), with indirect effect of 0.028 (Bootstrapped-CI: 0.008-0.047).Association of early-onset T2DM with cognitive impairment is partly mediated by diminished vascular compliance. Appropriate screening and assessment of cognitive function is important for early intervention and management of cognitive impairment.

Background real-world observations on the long-term benefits of Tai Chi (TC) exercise, in terms of physical and cognitive functioning, frailty, quality of life (QOL) and mortality are lacking. Methods prospective cohort study participants were community-dwelling adults aged 55+, including 5,407 non-frequent TC participants ( Results frequent TC participation was associated with 0.7-fold lower prevalence of impaired physical QOL [95% confidence interval (CI) = 0.57–0.91], decreased 0.4-fold odds of incident prefrailty/frailty among robust participants at baseline and 0.7-fold odds of impaired mental QOL at follow-up among participants with normal mental QOL at baseline. Lower odds of mortality risk (HR = 0.89, 95%CI = 0.72–1.09) were not significant after controlling for socioeconomic, behavioural and health factors. Composite indexes of physical functional and neurocognitive performance were maintained at high level or increased at follow-up among frequent TC participants. Conclusion TC exercise practised among community-dwelling older adults is associated with better physical, cognitive and functional wellbeing.

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.

Although gait variability has been linked to cognitive decline among older adults, the lack of a comprehensive composite gait variability score has dampened the application of gait variability.Does the enhanced gait variability index (EGVI) - a composite score gait variability index - provide differential and useful information on cognitive decline in community-dwelling adults from that using gait speed?Healthy community-dwelling adults (n = 311) aged 21-90 were individually administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Habitual gait speed and spatiotemporal parameters were measured using a 6 m instrumented walkway system. The EGVI for each participant was calculated from five spatiotemporal parameters - step length(cm), step time(s), stance time(s), single support time(s) and stride velocity(cm/s). Linear regression models, controlling for age, gender, and education, were built to examine the independent effects of EGVI or gait speed on global cognition and individual domains.Multiple regression revealed that gait speed contributed significantly to the performance of the domain "Attention" (p = 0.04) whereas EGVI contributed significantly for the performance of the domain "Visuospatial" (p = 0.04) and "Delayed Memory" (p = 0.02).EGVI provides differential and useful information from using gait speed alone. The EGVI may offer a solution to measure or track GV changes in relation to cognitive changes.

The association between pro-inflammatory cytokines and depression is widely acknowledged. However, longitudinal data that show they lead to depression are few. In a community-based sample of older individuals (n = 2761, ages = 55-98 y) in the Singapore Longitudinal Ageing Study (SLAS), we analyzed the associations between inflammatory markers (CRP, IL6, TNFα, and inflammation risk score) and depression (defined as the presence of depressive symptoms, depression history or treatment). Cross-sectional analysis showed that CRP, IL-6 and TNFα were significantly associated with depression at baseline. Longitudinal analysis controlling for a host of potentially confounding risk factors and initial depression revealed that IL-6, TNFα, and inflammation risk score were associated with elevated risk of depression at follow-ups. However, there was no significant association between CRP and subsequent depression after adjusting for sociodemographic, lifestyles and inflammatory medical condition variables. In summary, this prospective study shows that inflammation predicts depression in older adults, and suggests that the heterogeneous findings among studies may be due to differences in study population characteristics, depression, inflammatory markers, and the extent of adjusting for confounders.

Mental ill-health prolongs and complicates other chronic illnesses, which is a major public health concern because of the potential stress it places on health systems. Prevention via active aging and place-based interventions thus became increasingly important with population aging, e.g., through health promotion and age-friendly neighborhoods. However, how the targeted outcomes of these efforts are related remains unclear. This paper examined whether the relationship between active living and mental health or health-related quality of life is mediated by neighborhood cohesion. Cross-sectional data were drawn from n = 270 community-dwelling adults aged 50 and above in the Gerontology Research Program—Center for Ageing Research in the Environment (GRP-CARE) Survey. Path analysis showed that one can live actively for better mental health (Btotal = 0.24), but it is largely mediated by neighborhood cohesion (37%). Further examination of the factors of neighborhood cohesion showed that this mediation is explained by communal affordance (Bindirect = 0.05) and neighborhood friendship (Bindirect = 0.05). Additional study of the association between these mediators and factors of mental health revealed two psychosocial processes: (1) better community spaces (e.g., greenery and third places) support communal living (B = 0.36) and help older adults obtain emotional support (B = 0.32) for greater autonomy (B = 0.25); (2) spending more time outdoors enhances neighborhood friendship (B = 0.33) and interpersonal skills (B = 0.37), which in turn improves coping (B = 0.39). In short, the effects of active living on health are limited by one’s neighborhood environment. Neighborhood cohesion must be considered or it may stifle individual and policy efforts to age actively and healthily in urban environments. Context-sensitive implementations are required.

The potential neurocognition protective effects of dietary curcumin in curry consumed with food was investigated in this study of 2734 community-dwelling adults (aged ≥ 55, mean ± SD: 65.9 ± 7.4). We analyzed longitudinal data of baseline curry consumption (“never or rarely”, “occasionally”: once a month and once a week or daily) and baseline and 4.5-year follow-up cognitive function in mixed model analyses controlling for confounding risk factors. Significant between-exposure differences were found for Digit Span-Backward (DS-B), Verbal Fluency-Animals (VF-A) and Block Design (BD). Compared to “never or rarely” consumption, “very often” and “often” consumptions were associated with higher DS-B performance; “very often”—with higher VF-A, and “occasional”, “often” and “very often” consumptions—with higher BD: Cohen’s d: from 0.130 to 0.186. Among participants with cardiometabolic and cardiac diseases (CMVD), curry consumption was associated with significantly higher DS-B and VF-A. Among CMVD-free participants, curry consumption was associated with significantly higher DS-B, VF-A and BD: Cohen’s d: from 0.098 to 0.305. The consumption of dietary curcumin was associated with the maintenance over time of higher functioning on attention, short-term working memory, visual spatial constructional ability, language and executive function among community-dwelling older Asian adults.

Contains fulltext : 287762.pdf (Publisher’s version ) (Open Access) BACKGROUND: Poor social connections (eg, small networks, infrequent interactions, and loneliness) are modifiable risk factors for cognitive decline. Existing meta-analyses are limited by reporting aggregate responses, a focus on global cognition, and combining social measures into single constructs. We aimed to investigate the association between social connection markers and the rate of annual change in cognition (ie, global and domain-specific), as well as sex differences, using an individual participant data meta-analysis. METHODS: We harmonised data from 13 longitudinal cohort studies of ageing in North America, South America, Europe, Africa, Asia, and Australia. Studies were eligible for inclusion if they had baseline data for social connection markers and at least two waves of cognitive scores. Follow-up periods ranged from 0 years to 15 years across cohorts. We included participants with cognitive data for at least two waves and social connection data for at least one wave. We then identified and excluded people with dementia at baseline. Primary outcomes were annual rates of change in global cognition and cognitive domain scores over time until final follow-up within each cohort study analysed by use of an individual participant data meta-analysis. Linear mixed models within cohorts used baseline social connection markers as predictors of the primary outcomes. Effects were pooled in two stages using random-effects meta-analyses. We assessed the primary outcomes in the main (partially adjusted) and fully adjusted models. Partially adjusted models controlled for age, sex, and education; fully adjusted models additionally controlled for diabetes, hypertension, smoking, cardiovascular risk, and depression. FINDINGS: Of the 40 006 participants in the 13 cohort studies, we excluded 1392 people with dementia at baseline. 38 614 individual participants were included in our analyses. For the main models, being in a relationship or married predicted slower global cognitive decline (b=0·010, 95% CI 0·000-0·019) than did being single or never married; living with others predicted slower global cognitive (b=0·007, 0·002-0·012), memory (b=0·017, 0·006-0·028), and language (b=0·008, 0·000-0·015) decline than did living alone; and weekly interactions with family and friends (b=0·016, 0·006-0·026) and weekly community group engagement (b=0·030, 0·007-0·052) predicted slower memory decline than did no interactions and no engagement. Never feeling lonely predicted slower global cognitive (b=0·047, 95% CI 0·018-0·075) and executive function (b=0·047, 0·017-0·077) decline than did often feeling lonely. Degree of social support, having a confidante, and relationship satisfaction did not predict cognitive decline across global cognition or cognitive domains. Heterogeneity was low (I(2)=0·00-15·11%) for all but two of the significant findings (association between slower memory decline and living with others [I(2)=58·33%] and community group engagement, I(2)=37·54-72·19%), suggesting robust results across studies. INTERPRETATION: Good social connections (ie, living with others, weekly community group engagement, interacting weekly with family and friends, and never feeling lonely) are associated with slower cognitive decline. FUNDING: EU Joint Programme-Neurodegenerative Disease Research grant, funded by the National Health and Medical Research Council Australia, and the US National Institute on Aging of the US National Institutes of Health.

Introduction: The detection of systemic risk factors aids in the formulation of strategies to prevent multimorbidity and its associated mortality impact. We aimed to determine the associations of inflammatory, metabolic, malnutrition, and frailty indexes with multimorbidity onset and progression and their predictions of multimorbidity-associated mortality risk. Methods: A prospective cohort study (Singapore Longitudinal Aging Study [SLAS]) of 5,089 community-dwelling older adults aged ≥55 years in two waves of recruitment (SLAS-1: March 2005-September 2007, SLAS-2: January 2013-August 2018). Baseline variables included inflammatory (neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR)) and metabolic profiles (atherogenic index of plasma (AIP), triglyceride-glucose index of insulin resistance (TyG)), physical frailty, and nutritional risk (Mini Nutritional Assessment-Short Form (MNA-SF), Nutritional Screening Initiative (NSI), Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA)). At follow-up, 3–5 years after the baseline interview, incident multimorbidity (≥2 chronic diseases) was determined among multimorbidity-free participants (N = 1,657) and worsening multimorbidity (increase of ≥2 chronic diseases) among participants with baseline multimorbidity (N = 1,207). Mortality in all participants and those with multimorbidity (N = 2,291) was determined up to 31 December, 2016. Odds ratio (OR), hazard ratio (HR), and 95% confidence intervals (95% CI) were estimated in multivariate logistic and Cox regression models, in base model adjustments for age, sex, ethnicity, housing type, smoking, and a number of comorbidities, and further stepwise selection adjustment for other systemic risk indexes. Results: At baseline, NLR, LMR, AIP, TyG, physical frailty, ENIGMA, NSI, and MNA-SF were significantly associated with prevalent multimorbidity (p < 0.001). Among multimorbidity-free participants, LMR, TyG, and ENIGMA were significantly associated with incident multimorbidity in both the base model and further stepwise selection models: LMR (OR = 0.87, 95% CI: 0.81–0.94), TyG (OR = 1.36, 95% CI: 1.06–1.75), and ENIGMA (OR = 1.15, 95% CI: 1.02–1.30). Among participants with baseline multimorbidity, NLR, LMR, and TyG significantly predicted worsened multimorbidity at follow-up in base model analysis, and LMR (OR = 0.72, 95% CI: 0.60–0.86) and TyG (OR = 1.96, 95% CI: 1.24–3.09) remained as independent predictors in further stepwise selection models. Among participants with prevalent multimorbidity, NLR, TyG, frailty, MNA, and ENIGMA were significantly associated with mortality risk with base model adjustments and further stepwise selection models: NLR (HR = 1.20, 95% CI: 1.10–1.32), TyG (HR = 1.27, 95% CI: 1.04–1.54), frailty (HR = 1.22, 95% CI: 1.10–1.36), ENIGMA (HR = 1.13, 95% CI: 1.05–1.22), MNA (HR = 0.91, 95% CI: 0.85–0.97). A combined systemic risk index shows increasing quartiles, adjusted for age, sex, housing, and smoking status, significantly predicting mortality risk. Discussion/Conclusion: The onset and progression of multimorbidity and its mortality impact are driven by systemic factors, including inflammation, metabolic dysfunction (insulin resistance), malnutrition, and frailty. The measurement of these systemic factors using simple, inexpensive clinical and blood chemistry tools can help in strategies to prevent and reduce its mortality impact.

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.

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.

The link between pathogen exposure and mental health has long been hypothesized, but evidence remains limited. We investigated the association of seropositivity to common pathogens and total pathogen burden with depression and mental health and explored the role of mediating inflammatory cytokines. We profiled in 884 participants in the Singapore Longitudinal Ageing Studies, mean (SD) age: 67.9 (8.1) years, their seropositivities for 11 pathogens (CMV, HSV 1, HSV 2, HHV-6, EBV, VZV, RSV, Dengue, Chikungunya, H. Pylori and Plasmodium) and pathogen burden, Geriatric Depression Scale (GDS) score at baseline and 3-4 and 6-8 years follow-up, and baseline Mental Component Score (MCS) of 12-Item Short Form Survey (SF-12). Inflammatory markers included CRP, TNF-α, IL-6, MIP-1α, sgp130, sTNF-RI, sTNF-RII, C3a, and MCP-2. Controlling for age, sex, ethnicity, education, marital status, living alone, and smoking status, high pathogen burden (7 + cumulative infections) compared to low pathogen burden (1-5 cumulative infections) was significantly associated with period prevalence (the highest GDS score from baseline and follow-up measurements) of depressive symptoms (OR = 2.36, 95% CI = 1.05-5.33) and impaired mental health (OR = 2.25, 95% CI = 1.18-4.30). CMV seropositivity and HSV1 seropositivity, which are highly prevalent and most widely studied, were associated with estimated 2-fold increased odds of depression, but only HSV1 seropositivity was significantly associated with depression after adjusting for confounders. Notably, adjusted for confounders, RSV, H. pylori and Plasmodium seropositivity were significantly associated with increased odds, and Dengue seropositivity was associated with unexpectedly deceased odds of depressive symptoms and impaired mental health. The association of pathogen exposure with depression and mental health were at least in parts explained by inflammatory markers. Adding certain inflammatory markers to the models attenuated or weakened the association. Bootstrap method showed that MIP-1α significantly mediated the association between pathogen burden and mental health. In conclusion, lifelong pathogen burden and specific infections are associated with depression and impaired mental health in older adults.

Physical frailty commonly is associated with COPD, and its evaluation in COPD may provide important prognostic information for risk stratification.What are the comorbid associations of physical frailty with COPD? Does physical frailty singly and in combination with FEVProspective cohort study of community-dwelling adults 55 years of age or older in the Singapore Longitudinal Ageing Study. Baseline data of 1,162 participants with COPD and 3,465 participants without COPD included physical frailty, FEVBaseline prevalence of prefrailty (48.8%) and frailty (6.8%) in participants with COPD were significantly higher than in participants without COPD: frailty OR, 1.61; 95% CI, 1.15-2.26. Prefrailty or frailty was associated significantly with twofold increased odds of prevalent and incident IADL and basic ADL disability and mortality in participants with COPD. In combination with FEVThe study supports the use of physical frailty in addition to lung function and dyspnea in multidimensional evaluation of COPD.

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

Background ad hoc approaches are used to create composite indexes of intrinsic capacity (IC) based on five domains recommended by the World Health Organization for healthy ageing. We examined how combinations of domain-specific measures determine measurement performances of composite IC indexes. Methods in this population-based prospective cohort study, community-dwelling older persons (N = 2,906) aged 55 years and above were recruited. We used 12 domain-specific measures: cognition (Mini-Mental State Examination, MMSE), psychological (Geriatric Depression Scale, GDS), locomotion (Timed Up-and Go [TUG], GV, Knee Extension Strength, Performance Orientated Mobility Assessment), sensory (logarithm of the Minimum Angle of Resolution [LogMAR] vision and Whisper Test hearing) and vitality (forced expiratory volume in 1 second pulmonary function, Elderly Nutritional Indicators for Geriatric Malnutrition Assessment [ENIGMA], Nutritional Screening Initiative) to derive 144 composite 2- to 5-domain functional health indexes (FHI), and evaluated their abilities to predict 9-year mortality and their associations with health determinants. Results with 5-domain FHI, TUG, logMAR and MMSE showed the largest factor loadings (0.65–0.75). All single-domain FHI were significantly associated with mortality risks. Area under the receiver operating characteristic curve (AUC) values of mortality prediction increased with the number of domains (from mean 0.615 for single-domain FHI to mean 0.705 for 5-domain FHI), but the difference between 3-domain versus 4-domain FHI (P = 0.082) or versus 5-domain FHI (P = 0.109) was not statistically significant. Highest AUCs (P Conclusions among Singaporean older adults, cognition, sensory and locomotion are predominant IC domains. A multi-domain IC index performs better with more domain measures, but a minimalist 3-domain index performs just as robustly as a 4- or 5-domain index.

Measures of functional status are known to predict mortality more strongly than traditional disease risk markers in old adult populations. Few studies have compared the predictive accuracy of physical and functional measures for long-term mortality. In this prospective cohort study, community-dwelling older adults (N = 2906) aged 55 + (mean age 66.6 ± 7.7 years) were followed up for mortality outcome up to 9 years (mean 5.8 years). Baseline assessments included Timed Up-and-Go (TUG), gait velocity (GV), knee extension strength, Performance Oriented Mobility Assessment, forced expiratory volume in 1 second, Mini-Mental State Examination (MMSE), Geriatric Depression Scale, frailty, and medical morbidity. A total of 111 (3.8%) participants died during 16976.7 person-years of follow up. TUG was significantly associated with mortality risk (HR = 2.60, 95% CI = 2.05–3.29 per SD increase; HR = 5.05, 95% CI = 3.27–7.80, for TUG score ≥ 9 s). In multivariate analysis, TUG remained significantly associated with mortality (HR = 1.64, 95% CI = 1.20–2.19 per SD increase; HR = 2.66, 95% CI = 1.67–4.23 for TUG score ≥ 9 s). In multivariable analyses, GV, MMSE, Frailty Index (FI) and physical frailty, diabetes and multi-morbidity were also significantly associated with mortality. However, TUG (AUC = 0.737) demonstrated significantly higher discriminatory accuracy than GV (AUC = 0.666, p < 0.001), MMSE (AUC = 0.63, p < 0.001), FI (AUC = 0.62, p < 0.001), physical frailty (AUC = 0.610, p < 0.001), diabetes (AUC = 0.582, p < 0.001) and multi-morbidity (AUC = 0.589, p < 0.001). TUG’s predictive accuracy shows surpassing predictive accuracy for long-term mortality in community-dwelling older adults.

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.