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.

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.

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.

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.

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).