Digits in noise testing in a multilingual sample of Asian adults.

OBJECTIVE: Appropriate speech-in noise assessment is challenging in multilingual populations. This study aimed to assess whether first preferred language affected performance on an English Digits-in-noise (DIN) test in the local Asian multilingual population, controlling for hearing threshold, age, sex, English fluency and educational status. A secondary aim was to determine the association between DIN test scores and hearing thresholds. DESIGN: English digit-triplets in noise testing and pure-tone audiometry were conducted. Multiple regression analysis was performed with DIN scores and hearing thresholds as dependent variables. Correlation analysis was performed between DIN-SRT and hearing thresholds. STUDY SAMPLE: 165 subjects from the Singapore Longitudinal Ageing Study, a population-based longitudinal study of community-dwellers over 55 years of age. RESULTS: Mean DIN speech reception threshold (DIN-SRT) was -5.7 dB SNR (SD 3.6; range 6.7 to -11.2). Better ear pure tone average and English fluency were significantly associated with DIN-SRT. CONCLUSIONS: DIN performance was independent of first preferred language in a multilingual ageing Singaporean population after adjusting for age, gender and education. Those with poorer English fluency had a significantly lower DIN-SRT score. The DIN test has the potential to provide a quick, uniform method of testing speech in noise in this multilingual population.

Associations of Inflammatory, Metabolic, Malnutrition, and Frailty Indexes with Multimorbidity Incidence and Progression, and Mortality Impact: Singapore Longitudinal Aging Study.

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.

The Healthy Ageing Questionnaire Index: Validation in the Singapore Longitudinal Ageing Study.

INTRODUCTION: Healthy ageing (HA) indices typically use full questionnaire, performance- or blood-based assessment of functional ability which are time-consuming and resource-intensive. We developed and validated a simple and brief Healthy Ageing Questionnaire (HAQ) index with comparable measurement accuracy. METHODS: The 15-item HAQ (scored 0-100) was developed using data of 500 participants in the Singapore Study of Successful Ageing (SSOSA), a sub-cohort of the Singapore Longitudinal Ageing Study (SLAS-2). Its construct, concurrent, and predictive validity were evaluated in 2,161 participants in the SLAS-2 who were non-participants of the SSOSA. RESULTS: The HAQ index (mean = 64.0, SD = 11.8) showed a coherent 3-factor structure (Cronbach's alpha = 0.735). HAQ scores were higher among participants who were female, highly educated, not living alone, non-smoking, non-alcohol drinkers, not at risk of malnutrition, were robust or pre-frail, not disabled, had no or <5 medical conditions, and no recent fall or hospitalization. It was positively correlated with Mini-Mental State Examination and life satisfaction, and negatively correlated with age, logMAR vision, 5 times sit-and-stand, and timed-up-and-go. The HAQ index was significantly correlated but showed modest concordance with the Rowe-Kahn SA index. Increasing HAQ index quintiles were associated with decreased mortality risks from 40.6 to 9.7 deaths per 1,000 person-years; covariate-adjusted hazard ratio for the highest Q5 levels (HAQ score >70) was 0.44 (95% CI = 0.28-0.67). Using receiver operating characteristics analysis of predictive accuracy for survival, the area under the curve of HAQ was 0.675, and Rowe-Kahn SA index was 0.660 (p = 0.361). CONCLUSION: The HAQ is a brief and accurate HA index that is potentially useful across diverse settings and purposes in research, healthcare, and policy-making.

Risk Factors of Progression to Cognitive Frailty: Singapore Longitudinal Ageing Study 2.

INTRODUCTION: Cognitive frailty is associated with higher risk of dementia and adverse health outcomes. However, multidimensional factors that influence cognitive frailty transitions are not known. We aimed to investigate risk factors of incident cognitive frailty. METHODS: Prospective cohort study participants were community-dwelling adults without dementia and other degenerative disorders and baseline and follow-up, including N = 1,054 participants aged ≥55 free of cognitive frailty at baseline, with complete baseline (March 6, 2009, to June 11, 2013) and follow-up data at 3-5 years later (January 16, 2013, to August 24, 2018). Incident cognitive frailty was defined by one or more criteria of the physical frailty phenotype and <26 of Mini-Mental State Examination (MMSE) score. Potential risk factors assessed at baseline included demographic, socioeconomic, medical, psychological and social factors, and biochemical markers. Data were analyzed using least absolute shrinkage selection operator (LASSO) multivariable logistic regression models. RESULTS: A total of 51 (4.8%) participants, including 21 (3.5%) of the cognitively normal and physically robust participants, 20 (4.7%) of the prefrail/frail only, and 10 (45.4%) of cognitively impaired only, transited to cognitive frailty at follow-up. Risk factors for transition to cognitive frailty were having eye problem (OR = 2.6, 95% CI 1.24-5.43) and low HDL cholesterol (OR = 4.1, 95% CI 2.03-8.40), while protective factors for cognitive frailty transition were higher levels of education (OR = 0.3, 95% CI 0.10-0.74) and participation in cognitive stimulating activities (OR = 0.4, 95% CI 0.17-0.82). CONCLUSION: Multi-domain modifiable factors especially related to leisure activities predict cognitive frailty transition and may be targeted for prevention of dementia and associated adverse health outcomes.

Physiological and Cognitive Determinants of Gait Variability of Asian Population: The Yishun Study.

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 (ß = -0.19), faster hand reaction (ß = 0.12), and greater HGS (ß = -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.

Happy people live longer because they are healthy people.

OBJECTIVES: Higher levels of happiness are associated with longer life expectancy. Our study assessed the extent to which various factors explain the protective effect of happiness on all-cause mortality risk, and whether the association differs between older men and women. METHODS: Using data from the Singapore Longitudinal Aging Studies (N = 6073) of community-dwelling older adults aged ≥ 55 years, we analyzed the association of baseline Likert score of happiness (1 = very sad to 5 = very happy) and mortality from mean 11.7 years of follow up. Cox regression models were used to assess the extent to which confounding risk factors attenuated the hazard ratio of association in the whole sample and sex-stratified analyses. RESULTS: Happiness was significantly associated with lower mortality (p < .001) adjusted for age, sex and ethnicity: HR = 0.85 per integer score and HR = 0.57 for fairly-or-very happy versus fairly-or-very sad. The HR estimate (0.90 per integer score) was modestly attenuated (33.3%) in models that included socio-demographic and support, lifestyle or physical health and functioning factor, but remained statistically significant. The HR estimate (0.94 per integer score) was substantially attenuated (60%) and was insignificant in the model that included psychological health and functioning. Including all co-varying factors in the model resulted in statistically insignificant HR estimate (1.04 per integer score). Similar results were obtained for HR estimates for fairly-to-very happy versus fairly-to- very sad). DISCUSSION: Much of the association between happiness and increased life expectancy could be explained by socio-demographic, lifestyle, health and functioning factors, and especially psychological health and functioning factors.

Dose-response relationship between late-life physical activity and incident dementia: A pooled analysis of 10 cohort studies of memory in an international consortium.

INTRODUCTION: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear. METHODS: 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. RESULTS: 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). DISCUSSION: 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.

Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium.

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

Social connections and risk of incident mild cognitive impairment, dementia, and mortality in 13 longitudinal cohort studies of ageing.

INTRODUCTION: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. METHODS: We used individual participant data (N = 39271, Mage  = 70.67 (40-102), 58.86% female, Meducation  = 8.43 years, Mfollow-up  = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally. HIGHLIGHTS: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.

Lifetime pathogen burden, inflammatory markers, and depression in community-dwelling older adults.

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.

The Elderly Nutritional Index for Geriatric Malnutrition Assessment (ENIGMA): concurrent, construct and predictive validity in an external evaluation cohort of community-dwelling older persons.

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.

Functional health index of intrinsic capacity: multi-domain operationalisation and validation in the Singapore Longitudinal Ageing Study (SLAS2).

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 < 0.001) of best performing FHI were single-domain TUG: 0.735; 2-domain TUG + ENIGMA: 0.743; 3-domain TUG + LogMAR + ENIGMA: 0.762; 4-domain TUG + MMSE + LogMAR + ENIGMA: 0.757; 5-domain TUG + MMSE + GDS + LogMAR + ENIGMA: 0.751. FHI showed excellent construct validity based on correlations with known health determinants. 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.

Association of Tai Chi exercise with physical and neurocognitive functions, frailty, quality of life and mortality in older adults: Singapore Longitudinal Ageing Study.

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 (<1x/week) and 572 frequent TC participants (≥1x/week). Outcome measures at baseline and 3-5 years follow-up included physical performance (Knee Extension Strength, POMA Balance and Gait, Timed-up-and-go, Gait Speed) and neurocognitive performance (attention and working memory, visual-motor tracking and mental flexibility, verbal learning and memory, visual memory, spatial and constructional ability), Frailty Index ≥0.10, impaired QOL (SF12 physical and mental component) and all-cause mortality from mean 13 years follow-up. Effect estimates were adjusted for socio-demographics, other physical activities, nutritional risk and presence of cardiometabolic diseases. 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.

Functional mobility decline and incident mild cognitive impairment and early dementia in community-dwelling older adults: the Singapore Longitudinal Ageing 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).

Cardiometabolic and Vascular Disease Factors and Mild Cognitive Impairment and Dementia.

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.

Longitudinal associations of housework with frailty and mortality in older adults: Singapore Longitudinal Ageing Study 2.

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.

Associations of low handgrip strength and hand laterality with cognitive function and functional mobility - the Yishun Study.

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 < 28 kg for men and < 18 kg for women. Participants with HGS above 10% stronger on either hand were considered as having HGS asymmetry. Multiple linear regression models were adjusted for sociodemographic, smoking, education, comorbidity count, physical activity participation, obesity, self-rated health and hand dominance. RESULTS: Low HGS, but not asymmetry, was independently associated with lower functional mobility performance (ß = 1.3, 95%CI = 0.6,1.9), global cognitive function (ß = -10.4, 95%CI = -17.0,-3.8), immediate (ß = -2.6, 95%CI = -4.5,-0.7) and delayed (ß = -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.

Malnutrition Risk and Kidney Function and Decline in Community-Dwelling Older Adults.

OBJECTIVES: 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. DESIGN AND METHODS: 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 (eGFR > 60 mL/min/1.73 m2) at baseline (N = 786) who were followed up at 3-5 years. RESULTS: In 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 m2 respectively, and increasing CKD odds ratios of 1.81, 2.18, and 3.11 respectively. In longitudinal analysis, low, moderate, and high MR was significantly associated with increased risk of eGFR (>25%) decline (odds ratio of 2.37, 3.34, and 2.18 respectively). CONCLUSIONS: Among 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.

Atrial Fibrillation and the Prognostic Performance of Biomarkers in Heart Failure.

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.

Primary Care Prognostic (PCP) Index of 11-Year Mortality Risk: Development and Validation of a Brief Prognostic Tool.

BACKGROUND: Healthcare providers use a life expectancy of at least 5 to 10 years in shared clinical decision-making with older adults about cancer screening, major surgeries, and disease prevention interventions. At present, few prognostic indexes predict long-term mortality beyond 10 years or are suited for use in primary care settings. OBJECTIVE: We developed and validated an 8-item multidimensional index predicting 11-year mortality for use in primary care. DESIGN, SETTING, AND PARTICIPANTS: Using data from the Singapore Longitudinal Ageing Studies (SLAS), we developed a Primary Care Prognostic (PCP) Index for predicting 11-year mortality risk in a development cohort (n = 1550) and validated it in a geographically different cohort (n = 928). MAIN MEASURES: The PCP Index was derived from eight indicators (body mass loss, weakness, slow gait, comorbidity, polypharmacy, IADL/BADL dependency, low albumin, low total cholesterol, out of 25 candidate indicators) using stepwise Cox proportional hazard models. KEY RESULTS: In the developmental cohort, the mortality hazard ratio increased by 53% per PCP point score increase, independent of age and sex. Across risk categories, absolute risks of mortality increased from 5% (score 0) to 67.9% (scores 7-9), with area under curve (AUC = 0.77 (95% CI 0.73-0.80)). The PCP Index also predicted mortality in the validation cohort, with AUC = 0.70 (95% CI 0.64-0.75). CONCLUSIONS: The PCP Index using simple clinical assessments and point scoring is a potentially useful prognostic tool for predicting long-term mortality and is well suited for risk stratification and shared clinical decision-making with older adults in primary care.