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.

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.

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.

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.

The Neighborhood Built Environment and Cognitive Function of Older Persons: Results from the Singapore Longitudinal Ageing Study.

BACKGROUND: We investigated the association of subjective (perceived) and objective (geographical information system [GIS]-based) measures of the neighborhood built environment (BE) attributes with cognitive function among older persons, and the mediating effect of transportation physical activity (TPA) and leisure time (physical, social and productive) activities (LTA). METHOD: A cross-sectional study of 402 residents aged 55 years and above in the Singapore Longitudinal Ageing Study. Perceived neighborhood BE attributes (residential density, street connectivity, land use mix - diversity, land use mix - access, infrastructure for walking or cycling, aesthetics, traffic safety, and crime safety) and objective GIS measures of walkability and accessibility were related to participants' cognitive global and domain-specific performance measured by Repeatable Battery for the Assessment of Neurocognitive Status (RBANS). RESULTS: Controlling for age, sex, education, race, chronic medical illnesses, self-rated health, Geriatric Depression Scale depression score, POMA measures of balance and gait, and other BE attributes, the subjective measure of land use mix-diversity (standardized coefficient ß = 0.161, p = 0.008) and GIS measure of walkability (ß = 0.163, p = 0.002) were positively and significantly associated with RBANS global z-score, and immediate and delayed memory recall, visuospatial/ constructional ability and language, except attention. In hierarchical modeling, TPA and LTA attenuated the effect estimates, but the associations remained significant. CONCLUSION: BE features which increase opportunities and easy access to a diversity of destinations for services and facilities that promote physical, social and cognitively stimulating activities is associated with better cognitive functioning in older people.

Hearing Loss and Risk of Mild Cognitive Impairment and Dementia: Findings from the Singapore Longitudinal Ageing Study.

AIM: To investigate the associations between hearing loss and prevalent and incident mild cognitive impairment (MCI), dementia and MCI or dementia (all cases). METHODS: Cross-sectional and longitudinal analyses of baseline and follow-up data were performed in a population-based cohort. The baseline sample of 2,599 adults aged ≥55 included 1,515 cognitively normal subjects who were followed up to 8 years. Hearing loss at baseline was determined by the whispered voice test, and MCI and dementia by Mini-Mental State Examination screening, Clinical Dementia Rating scale, neurocognitive tests, MRI, and panel consensus diagnosis. RESULTS: Hearing impairment was associated with increased prevalence of dementia (odds ratio = 3.63, 95% confidence interval [CI] 1.16-11.4, p = 0.027) but not MCI alone or all cases of MCI or dementia, adjusted for sex, age, ethnicity, education, central obesity, hypertension, diabetes, dyslipidemia, smoking, alcohol, leisure time activity, cardiac diseases, and depressive symptoms. Among participants who were cognitively normal at baseline, those with hearing impairment were more likely to develop MCI or dementia (hazard ratio [HR] = 2.30, 95% CI 1.08-4.92, p = 0.032). Hearing loss was associated with elevated but statistically nonsignificant estimates of adjusted HR (1.85, 95% CI 0.78-4.40) for incident MCI alone. CONCLUSIONS: Hearing loss is independently associated with prevalent dementia and incident MCI or dementia.

Unconditional and Conditional Standards Using Cognitive Function Curves for the Modified Mini-Mental State Exam: Cross-Sectional and Longitudinal Analyses in Older Chinese Adults in Singapore.

OBJECTIVE: The conventional practice of assessing cognitive status and monitoring change over time in older adults using normative values of the Mini-Mental State Exam (MMSE) based on age bands is imprecise. Moreover, population-based normative data on changes in MMSE score over time are scarce and crude because they do not include age- and education-specific norms. This study aims to develop unconditional standards for assessing current cognitive status and conditional standards that take prior MMSE score into account for assessing longitudinal change, with percentile curves as smooth functions of age. METHODS: Cross-sectional and longitudinal data of a modified version of the MMSE for 2,026 older Chinese adults from the Singapore Longitudinal Aging Study, aged 55-84, in Singapore were used to estimate quantile regression coefficients and create unconditional standards and conditional standards. RESULTS: We presented MMSE percentile curves as a smooth function of age in education strata, for unconditional and conditional standards, based on quantile regression coefficient estimates. We found the 5th and 10th percentiles were more strongly associated with age and education than were higher percentiles. Model diagnostics demonstrated the accuracy of the standards. CONCLUSION: The development and use of unconditional and conditional standards should facilitate cognitive assessment in clinical practice and deserve further studies.

Objective and subjective measures of neighborhood environment (NE): relationships with transportation physical activity among older persons.

BACKGROUND: This study examined the associations of subjective and objective measures of the neighbourhood environment with the transportation physical activity of community-dwelling older persons in Singapore. METHOD: A modified version of the Neighborhood Environment Walkability Scale (NEWS) and Geographical Information System (GIS) measures of the built environment characteristics were related to the frequency of walking for transportation purpose in a study sample of older persons living in high-density apartment blocks within a public housing estate in Singapore. Relevant measured variables to assess the complex relationships among built environment measures and transportation physical activity were examined using structural equation modelling and multiple regression analyses. RESULTS: The subjective measures of residential density, street connectivity, land use mix diversity and aesthetic environment and the objective GIS measure of Accessibility Index have positively significant independent associations with transportation physical activity, after adjusting for demographics, socio-economic and health status. CONCLUSION: Subjective and objective measures are non-overlapping measures complementing each other in providing information on built environment characteristics. For elderly living in a high-density urban neighborhood, well connected street, diversity of land use mix, close proximity to amenities and facilities, and aesthetic environment were associated with higher frequency of walking for transportation purposes.

Montreal Cognitive Assessment for screening mild cognitive impairment: variations in test performance and scores by education in Singapore.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) was developed as a screening instrument for mild cognitive impairment (MCI). We evaluated the MoCA's test performance by educational groups among older Singaporean Chinese adults. METHOD: The MoCA and Mini-Mental State Examination (MMSE) were evaluated in two independent studies (clinic-based sample and community-based sample) of MCI and normal cognition (NC) controls, using receiver operating characteristic curve analyses: area under the curve (AUC), sensitivity (Sn), and specificity (Sp). RESULTS: The MoCA modestly discriminated MCI from NC in both study samples (AUC = 0.63 and 0.65): Sn = 0.64 and Sp = 0.36 at a cut-off of 28/29 in the clinic-based sample, and Sn = 0.65 and Sp = 0.55 at a cut-off of 22/23 in the community-based sample. The MoCA's test performance was least satisfactory in the highest (>6 years) education group: AUC = 0.50 (p = 0.98), Sn = 0.54, and Sp = 0.51 at a cut-off of 27/28. Overall, the MoCA's test performance was not better than that of the MMSE. In multivariate analyses controlling for age and gender, MCI diagnosis was associated with a <1-point decrement in MoCA score (η(2) = 0.010), but lower (1-6 years) and no education was associated with a 3- to 5-point decrement (η(2) = 0.115 and η(2) = 0.162, respectively). CONCLUSION: The MoCA's ability to discriminate MCI from NC was modest in this Chinese population, because it was far more sensitive to the effect of education than MCI diagnosis.

Dietary and supplemental antioxidant and anti-inflammatory nutrient intakes and pulmonary function.

OBJECTIVE: A limited but growing body of evidence supports a significant role of antioxidant and anti-inflammatory micronutrients in pulmonary health. We investigated the associations of dietary and supplemental intakes of vitamins A, C, E and D, Se and n-3 PUFA with pulmonary function in a population-based study. DESIGN: Population-based, cross-sectional study and data analysis of fruits and vegetables, dairy products and fish, vitamins A, C, E and D, Se and n-3 PUFA supplemental intakes, pulmonary risk factors and spirometry. SUBJECTS: Chinese older adults (n 2478) aged 55 years and above in the Singapore Longitudinal Ageing Studies. RESULTS: In multiple regression models that controlled simultaneously for gender, age, height, smoking, occupational exposure and history of asthma/chronic obstructive pulmonary disease, BMI, physical activity, and in the presence of other nutrient variables, daily supplementary vitamins A/C/E (b = 0·044, SE = 0·022, P = 0·04), dietary fish intake at least thrice weekly (b = 0·058, SE = 0·016, P < 0·0001) and daily supplementary n-3 PUFA (b = 0·068, SE = 0·032, P = 0·034) were individually associated with forced expiratory volume in the first second. Supplemental n-3 PUFA was also positively associated with forced vital capacity (b = 0·091, SE = 0·045, P = 0·045). No significant association with daily dairy product intake, vitamin D or Se supplements was observed. CONCLUSIONS: The findings support the roles of antioxidant vitamins and n-3 PUFA in the pulmonary health of older persons.

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.

Systemic inflammation, depression and obstructive pulmonary function: a population-based study.

BACKGROUND: Levels of Interleukin-6 (IL-6) and C-creative protein (CRP) indicating systemic inflammation are known to be elevated in chronic diseases including chronic obstructive pulmonary disease (COPD) and depression. Comorbid depression is common in patients with COPD, but no studies have investigated whether proinflammatory cytokines mediate the association between pulmonary function and depressive symptoms in healthy individuals with no known history of obstructive pulmonary diseases. METHODS: In a population-based sample (n = 2077) of individuals aged 55 and above with no known history of obstructive pulmonary disease in the Singapore Longitudinal Ageing Study (SLAS), we analyzed the relationships between IL-6 and CRP, depressive symptoms (GDS-15 ≥5) and obstructive pulmonary function (FEV1% predicted and FEV1/FVC% predicted). RESULTS: High serum levels of IL-6 and CRP were associated with greater prevalence of depressive symptoms (p < 0.05). High IL-6, high CRP and depressive symptoms were independently associated with decreased FEV1% predicted and FEV1/FVC% predicted after adjusting for smoking status, BMI and number of chronic inflammatory diseases. Increasing grades of combination of inflammatory markers and/or depressive symptoms was associated with progressive increases in pulmonary obstruction. In hierarchical models, the significant association of depressive symptoms with pulmonary obstruction was reduced by the presence of IL-6 and CRP. CONCLUSIONS: This study found for the first time an association of depressive symptoms and pulmonary function in older adults which appeared to be partly mediated by proinflammatory cytokines. Further studies should be conducted to investigate proinflammatory immune markers and depressive symptoms as potential phenotypic indicators for chronic obstructive airway disorders in older adults.