Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life: An Individual Participant Data Meta-Analysis.

Importance: The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. Objectives: To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group. Data Source and Study Selection: Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece). Data Extraction and Synthesis: Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines. Main Outcomes and Measures: The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group. Results: The analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses. Conclusions and Relevance: This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.

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.

Lower insulin level is associated with sarcopenia in community-dwelling frail and non-frail older adults.

Background: Sarcopenia is common among older individuals with and without type 2 diabetes mellitus (T2DM). There are conflicting evidence in support of the role of insulin in the development of age-related and T2DM-related sarcopenia. We investigated the relationships between the levels of fasting insulin and other blood biomarkers related to insulin or lipid metabolism with the presence of sarcopenia in two independent studies. Materials and methods: In 246 pre-frail frail older individuals with (n = 41) and without T2DM (n = 205) in the Singapore Frailty Interventional Trial, sarcopenia was defined by low appendicular lean mass (ALM) relative to total body mass (skeletal muscle index, SMI = ALM/height2) and low lower limb strength or gait speed according to the Asian Working Group for Sarcopenia (AWGS) criteria released in 2019, and related to levels of fasting insulin and glucose, C-peptide, IGF-1, leptin, and active ghrelin. This investigation was validated in another independent study sample of 189 robust and pre-frail frail elderly in the Singapore Longitudinal Aging Study Wave 2 (SLAS-2). Results: Compared to non-sarcopenic individuals, those with sarcopenia and possible sarcopenia showed significantly lower fasting insulin (p < 0.05) in pre-frail/frail and non-frail older individuals. Consistent trends of relationships were observed for serum levels of C-peptide, IGF-1, leptin, and active ghrelin. In multivariable logistic regression models, sarcopenia was independently associated with low insulin (p < 0.05). Levels of fasting insulin, C-peptide, and leptin were also significantly associated with BMI, SMI, knee extension strength, gait speed, and physical activity score. Conclusion: Dysregulated insulin secretion in diabetic and non-diabetic older individuals may play an important role in age-related and diabetes-related sarcopenia.

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.

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.

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.

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.

Endoplasmic reticulum stress response and bile acid signatures associate with multi-strain seroresponsiveness during elderly influenza vaccination.

The elderly are an important target for influenza vaccination, and the determination of factors that underlie immune responsiveness is clinically valuable. We evaluated the immune and metabolic profiles of 205 elderly Singaporeans administered with Vaxigrip. Despite high seroprotection rates, we observed heterogeneity in the response. We stratified the cohort into complete (CR) or incomplete responders (IR), where IR exhibited signs of accelerated T cell aging. We found a higher upregulation of genes associated with the B-cell endoplasmic-reticulum stress response in CR, where XBP-1 acts as a key upstream regulator. B-cells from IR were incapable of matching the level of XBP-1 upregulation observed in CR after inducing ER stress with tunicamycin in vitro. Metabolic signatures also distinguished CR and IR - as CR presented with a greater diversity of bile acids. Our findings suggest that the ER-stress pathway activation could improve influenza vaccination in the elderly.

Effects of multi-domain lifestyle interventions on sarcopenia measures and blood biomarkers: secondary analysis of a randomized controlled trial of community-dwelling pre-frail and frail older adults.

Few studies have comprehensively described changes in blood biomarkers of the physiological responses underlying sarcopenia reduction associated with lifestyle interventions. In this study, we performed secondary analyses of data in a randomized controlled trial of multi-domain lifestyle interventions (6-month duration physical exercise, nutritional enrichment, cognitive training, combination and standard care control) among 246 community-dwelling pre-frail and frail elderly, aged ≥65 years, with and without sarcopenia. Appendicular lean mass (ALM), lower limb strength, gait speed, and blood levels of markers of muscle metabolism, inflammation, anti-oxidation, anabolic hormone regulation, insulin signaling, tissue oxygenation were measured at baseline, 3-month and 6-month post-intervention. Multi-domain interventions were associated with significant (p < 0.001) reduction of sarcopenia at 3-month and 6-month post-intervention, improved gait speed, enhanced lower limb strength, and were equally evident among sarcopenic participants who were slower at baseline than non-sarcopenic participants. Active intervention was associated with significantly reduced inflammation levels. Sarcopenia status and reduction were associated with blood biomarkers related to muscle metabolism, steroid hormone regulation, insulin-leptin signaling, and tissue oxygenation. Physical, nutritional and cognitive intervention was associated with measures of sarcopenia reduction, together with changes in circulating biomarkers of anabolic and catabolic metabolism underlying sarcopenia.

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.

Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment.

BACKGROUND: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). METHODS: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School. RESULTS: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers. CONCLUSION: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.

APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline.

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

Collaborative care for primary care treatment of late-life depression in Singapore: Randomized controlled trial.

BACKGROUND: The effectiveness and portability of the collaborative care model in the primary care treatment of depression has not been demonstrated in many randomized controlled trials in healthcare settings across the world. We determined the effectiveness of collaborative care management of elderly depression in the primary care setting in Singapore. METHOD: Eligible participants with depressive symptoms were randomized to 6-month duration usual care (UC, N = 112) or collaborative care (CC, N = 102). Outcome measures were HDRS-17, GDS, BDI and SF-12 MCS QOL measured at 3, 6, and 12-month, care satisfaction at 6-month, and also measured on 120 participants who refused referral (non-receipt of care, NC). Primary outcome was HDRS-17 measure of depression severity, response and remission at 6-month. RESULTS: HDRS scores in CC group compared to UC group were reduced more at 6-month (1.5 points difference in change from baseline), and also at 3 and 12-month, with similar observations of differences for GDS and BDI. There was significantly greater improvement for both CC and UC groups compared to NC group. The CC group was about 1.5 times more likely to show HDRS treatment response and remission, and more than two times likely to show GDS treatment response and remission than the UC and NC groups, as well as better quality of life improvement (P < .001) and better care satisfaction (P < .001). CONCLUSION: Collaborative care is effective for primary care treatment of older persons with depression and is portable in diverse health care settings.

Publisher Correction: The Extended Polydimensional Immunome Characterization (EPIC) web-based reference and discovery tool for cytometry data.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Association of Sedentary Behaviour and Cognitive Function in People Without Dementia: A Coordinated Analysis Across Five Cohort Studies from COSMIC.

BACKGROUND: Besides physical activity as a target for dementia prevention, sedentary behaviour is hypothesized to be a potential target in its own right. The rising number of persons with dementia and lack of any effective treatment highlight the urgency to better understand these modifiable risk factors. Therefore, we aimed to investigate whether higher levels of sedentary behaviour are associated with reduced global cognitive functioning and slower cognitive decline in older persons without dementia. METHODS: We used five population cohorts from Greece, Australia, USA, Japan, and Singapore (HELIAD, PATH, SALSA, SGS, and SLAS2) from the Cohort Studies of Memory in an International Consortium. In a coordinated analysis, we assessed the relationship between sedentary behaviour and global cognitive function with the use of linear mixed growth model analysis (mean follow-up range of 2.0-8.1 years). RESULTS: Baseline datasets combined 10,450 older adults without dementia with a mean age range between cohorts of 66.7-75.1 years. After adjusting for multiple covariates, no cross-sectional association between sedentary behaviour and cognition was found in four studies. One association was detected where more sedentary behaviour was cross-sectionally linked to higher cognition levels (SLAS2, B = 0.118 (0.075; 0.160), P < 0.001). Longitudinally, there were no associations between baseline sedentary behaviour and cognitive decline (P > 0.05). CONCLUSIONS: Overall, these results do not suggest an association between total sedentary time and lower global cognition in older persons without dementia at baseline or over time. We hypothesize that specific types of sedentary behaviour may differentially influence cognition which should be investigated further. For now, it is, however, too early to establish undifferentiated sedentary time as a potential effective target for minimizing cognitive decline in older adults without dementia.

Systemic and Metabolic Signature of Sarcopenia in Community-Dwelling Older Adults.

BACKGROUND: Evidence suggests the pivotal contribution of nutrition as a modifiable risk factor for sarcopenia. The present cross-sectional study characterized the nutritional and metabolic profile of sarcopenia through an extensive exploration of a wide array of blood biomarkers related to muscle protein metabolism and transcriptomic signatures in community-dwelling elderly adults. METHODS: Among 189 older individuals with a mean age of 73.2 years, sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia criteria based on appendicular lean mass measured by dual-energy X-ray absorptiometry scan, muscle strength, and gait speed. Nutritional status was evaluated using the mini-nutritional assessment (MNA). In addition, we assessed specific blood biomarkers of nutritional status (plasma essential amino acids [EAAs], vitamins), nicotine-derived metabolites, and an extensive microarray analysis from peripheral blood mononuclear cells. RESULTS: Malnutrition defined by low MNA score was independently associated with sarcopenia (p < .001). Sarcopenic elderly showed lower body mass index and leptin and higher adiponectin and high-density lipoproteins. Levels of EAAs including lysine, methionine, phenylalanine, threonine, as well as branched-chain AAs and choline, were inversely associated with sarcopenia. Furthermore, nicotine metabolites (cotinine and trans-3'-hydroxycotine) and vitamin B6 status were linked to one or more clinical and functional measures of sarcopenia. Differentially expressed genes and ingenuity pathway analysis supported the association of nutrition with sarcopenia. CONCLUSIONS: Herein, the characterization of a nutritional and metabolic signature of sarcopenia provides a firm basis and potential identification of specific targets and directions for the nutritional approach to the prevention and treatment of sarcopenia in aging populations.

Estimating Biological Age in the Singapore Longitudinal Aging Study.

BACKGROUND: Biological age (BA) is a more accurate measure of the rate of human aging than chronological age (CA). However, there is limited consensus regarding measures of BA in life span and healthspan. METHODS: This study investigated measurement sets of 68 physiological biomarkers using data from 2,844 Chinese Singaporeans in two age subgroups (55-70 and 71-94 years) in the Singapore Longitudinal Aging Study (SLAS-2) with 8-year follow-up frailty and mortality data. We computed BA estimate using three commonly used algorithms: Principal Component Analysis (PCA), Multiple Linear Regression (MLR), and Klemera and Doubal (KD) method, and additionally, explored the use of machine learning methods for prediction of mortality and frailty. The most optimal algorithmic estimate of BA compared to CA was evaluated for their associations with risk factors and health outcome. RESULTS: Stepwise selection procedures resulted in the final selection of 8 biomarkers in males and 10 biomarkers in females. The highest-ranking biomarkers were estimated glomerular filtration rate for both genders, and the forced expiratory volume in 1 second in males and females. The BA estimates robustly predicted frailty and mortality and outperformed CA. The best performing KD measure of BA was notably predictive in the younger group (aged 55-70 years). BA estimates obtained using a machine learning train-test method were not more accurate than conventional BA estimates in predicting mortality and frailty in most situations. Biologically older people with the same CA as biologically younger individuals had higher prevalence of frailty and 8-year mortality, and worse health, behavioral, and functional characteristics. CONCLUSIONS: BA is better than CA for measuring life span (mortality) and healthspan (frailty). This measurement set of physiological markers of biological aging among Chinese robustly differentiate biologically old from younger individuals with the same CA.