Curcumin-rich curry consumption and life expectancy: Singapore longitudinal ageing study.

The therapeutic potential of curcumin for many diseases are intensively investigated. However, real-world observational data documenting health and longevity effects associated with dietary curcumin in turmeric from consuming curry in food is lacking. A prospective cohort study of 4551 adults aged 55 + assessed curry consumption (never or < once/year, ≥ once/year to < once/month, ≥ once/month to < once/week, ≥ once/week to < daily, ≥ once daily), prevalent health conditions, blood biomarker indexes of atherogenicity, insulin resistance, and inflammation at baseline, and mean (SD) 11.6 (3.8) year follow up of all-cause, CVS and cancer mortality. There were linear positive associations of increasing curry consumption with waist circumference, fasting blood glucose, TyG, AIP, CRI-1, CRI-2, central obesity and diabetes prevalence, and inverse association with eGFR. There were non-linear associations with FEV1/height2 and COPD prevalence, GDS score and depression, MMSE score and cognitive impairment, comorbidity count, serum albumin and haemoglobin, being most favourable with moderate consumption. The levels of NLR, PLR and SII indices of systemic and immune inflammation decreased linearly with curry consumption. Total mortality HR adjusted for baseline co-variables, decreased across curry consumption, 0.68 (95%CI 0.56-0.82), 0.54 (95%CI 0.43-0.69), 0.70 (0.52-0.93), and 0.62 (0.41-0.95), being lowest in the middle categories. Among participants with cardio-metabolic and vascular diseases (CMVD), at least occasional curry consumption was associated with decreased mortality risk by 39%, and increased life expectancy by 1.0 years. Among those without CMVD, the associated life expectancy increase was 1.9 years. Moderate curry consumption may confer meaningful longevity benefits.

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.

Correlates of Gait Speed Among Older Adults From 6 Countries: Findings From the COSMIC Collaboration.

BACKGROUND: Few studies have compared gait speed and its correlates among different ethnogeographic regions. The goals of this study were to describe usual and rapid gait speed, and identify their correlates across Australian, Asian, and African countries. METHODS: We used data from 6 population-based cohorts of adults aged 65+ from 6 countries and 3 continents (N = 6 472), with samples ranging from 231 to 1 913. All cohorts are members of the Cohort Studies of Memory in an International Consortium collaboration. We investigated whether clinical (body mass index [BMI], hypertension, stroke, apolipoprotein status), psychological (cognition, mood, general health), and behavioral factors (smoking, drinking, physical activity) correlated with usual (N = 4 cohorts) and rapid gait speed (N = 3 cohorts) similarly across cohorts. Regression models were controlled for age, sex, and education, and were sex-stratified. RESULTS: Age- and sex-standardized usual gait speed means ranged from 0.61 to 1.06 m/s and rapid gait speed means ranged from 1.16 to 1.64 m/s. Lower BMI and better cognitive function consistently correlated with faster gait speed in all cohorts. Less consistently, not having hypertension and greater physical activity engagement were associated with faster gait speed. Associations with mood, smoking, and drinking were largely nonsignificant. These patterns were not attenuated by demographics. There was limited evidence that the associations differed by sex, except physical activity, where the greater intensity was associated with usual gait among men but not women. CONCLUSIONS: This study is among the first to describe the usual and rapid gait speeds across older adults in Africa, Asia, and Australia.

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.

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.

One-Carbon Metabolism Biomarkers and Risks of Incident Neurocognitive Disorder among Cognitively Normal Older Adults.

There is a lack of evidence supporting an association between folate and vitamin B12 exposure with cognitive outcomes. We examined serum folate and vitamin B12 and plasma homocysteine in 690 cognitively-normal adults (aged ≥ 55) from the Singapore Longitudinal Aging Study (SLAS-2) followed-up over 4.5 years on incident neurocognitive disorder (NCD): mild cognitive impairment (MCI) and dementia. At follow-up, 5.7% (39) of participants developed NCD (34 MCI and 5 dementia). Comparing with those who remained cognitively-normal, participants progressed to NCD had significantly lower mean baseline vitamin B12 (420 [SD ± 221] vs. 510 [SD ± 290] pmol/L, p = 0.026), higher homocysteine (14.6 [SD ± 4.2] vs. 12.9 [SD ± 4.3], p = 0.018) and lower one-carbon index (Z-scores: -0.444 [SD ± 0.819] vs. -0.001 [SD ± 0.990], p = 0.006). Adjusted for confounders, significant associations with incident NCD were found for lower vitamin B12 (per-SD OR = 2.10, 95%CI = 1.26-3.52), higher homocysteine (per-SD OR = 1.96, 95%CI = 1.18-3.24) and lower one-carbon index (per-SD OR = 1.67, 95%CI = 1.06-2.64). Folate was not significantly associated with progression to NCD. Notably, low B12 in the presence of high folate was significantly associated with incident NCD (adjusted OR = 3.81, 95%CI = 1.04-13.9). Low B12, high homocysteine, low B12 in the presence of high folate, and a one-carbon index of hypo-methylation were independently associated with progression to NCD among cognitively normal.

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).

Inflammatory markers and incident depression: Evidence in a population-based prospective study.

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.

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.

Curcumin-Rich Curry Consumption and Neurocognitive Function from 4.5-Year Follow-Up of Community-Dwelling Older Adults (Singapore Longitudinal Ageing Study).

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" consumptions­with 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.

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.

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.

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.

Co-occurrence of Physical Frailty and COPD and Association With Disability and Mortality: Singapore Longitudinal Ageing Study.

BACKGROUND: Physical frailty commonly is associated with COPD, and its evaluation in COPD may provide important prognostic information for risk stratification. RESEARCH QUESTIONS: What are the comorbid associations of physical frailty with COPD? Does physical frailty singly and in combination with FEV1 percent predicted and dyspnea predict disability and mortality? STUDY DESIGN AND METHODS: Prospective 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, FEV1 percent predicted, and dyspnea. Outcome measures were prevalent and incident instrumental activities of daily living (IADL) and basic activities of daily living (ADL) disability at 3 to 5 years of follow-up and all-cause mortality up to 11 years. ORs, hazard ratios, and 95% CIs were adjusted for socioeconomic status, smoking, and comorbidity count. RESULTS: Baseline 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 FEV1 percent predicted of < 80% or dyspnea, frailty was associated with substantially increased threefold to fourfold odds of prevalent and incident IADL and basic ADL disability, and twofold to threefold increased mortality hazard. A summary score combining physical frailty, FEV1 of < 80%, and dyspnea predicted steeper risk gradients of prevalent and incident IADL and basic ADL disability and mortality across four risk categories (0, 1, 2, 3-5), with the highest risk category predicting between sevenfold and 8.5-fold increased risks in crude analyses, which remained significantly high after covariate adjustment. INTERPRETATION: The study supports the use of physical frailty in addition to lung function and dyspnea in multidimensional evaluation of COPD.

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.

Physical and functional measures predicting long-term mortality in community-dwelling older adults: a comparative evaluation in the Singapore Longitudinal Ageing Study.

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.

Physiological Dysregulation, Frailty, and Impacts on Adverse Health and Functional Outcomes.

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

Malnutrition Risk, Physical Function Decline and Disability in Middle-Aged and Older Adults Followed Up in the Singapore Longitudinal Ageing Study.

PURPOSE: 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.