Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: The COSMIC consortium.

INTRODUCTION: White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions. METHODS: We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains. RESULTS: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing. CONCLUSION: The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.

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.

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: the COSMIC consortium.

INTRODUCTION: White matter hyperintensities (WMH) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well-documented in populations of different ethnicities and/or from different geographical regions. METHOD: Magnetic resonance imaging data of five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1,946) were examined for WMH and their associations with vascular risk factors and cognition. RESULT: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake and insufficient physical activity. Participants with moderate or higher physical activity had less WMH than those who never exercised, but the former two groups did not differ. Hypertension and stroke had stronger associations with WMH volumes in the White, compared to Asian subsample. DISCUSSION: The current study highlighted the ethnic differences in the contributions of vascular risk factors to WMH.

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.

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.

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.

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.

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.

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.

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.

Socio-Environmental, Lifestyle, Behavioural, and Psychological Determinants of Biological Ageing: The Singapore Longitudinal Ageing Study.

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

Metabolic Syndrome and Cognition: Follow-Up Study of Chinese Over-55-Year-Olds.

BACKGROUND/AIM: Studies of the associations of the metabolic syndrome (MetS) with cognitive function and decline are inconclusive. We investigated the associations of the MetS with cognitive functions in 823 Chinese >55-year-olds followed up over 4.5 years. METHODS: The relationships between the MetS and baseline and follow-up z-scores of cognitive domain functions were examined using mixed model analysis. RESULTS: There were specific inverse cross-sectional associations of single cardiometabolic risk factors with cognition, such as hyperglycemia with processing speed (p = 0.045). The MetS was negatively associated with 3 out of 4 cognitive domains (p = 0.018 to p = 0.003), and the count of cardiometabolic risk factors with all cognitive domains (p = 0.025 to p = 0.002). Longitudinally, dyslipidemia was associated with worse decline in memory and learning (p = 0.022). The count of cardiometabolic risk factors was associated with worse declines in cognition (p = 0.032 for global cognition). CONCLUSION: Among middle-aged and older Asians, an increased number of component cardiometabolic risk factors of the MetS was associated with a worse decline in cognitive function over time.