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To address the paucity of research investigating the implementation of multi-domain dementia prevention interventions, we implemented and evaluated a 24-week, bi-weekly multi-domain program for older adults at risk of cognitive impairment at neighborhood senior centres (SCs). It comprised dual-task exercises, cognitive training, and mobile application-based nutritional guidance. An RCT design informed by the Reach, Effectiveness, Adoption, Implementation, Maintenance framework was adopted. Outcome measures include cognition, quality of life, blood parameters, and physical performance. Implementation was evaluated through questionnaires administered to participants, implementers, SC managers, attendance lists, and observations. The program reached almost 50% of eligible participants, had an attrition rate of 22%, and was adopted by 8.7% of the SCs approached. It was implemented as intended; only the nutritional component was re-designed due to participants’ unfamiliarity with the mobile application. While there were no between-group differences in cognition, quality of life, and blood parameters, quality of life reduced in the control group and physical function improved in the intervention group after 24 weeks. The program was well-received by participants and SCs. Our findings show that a multi-domain program for at-risk older adults has benefits and can be implemented through neighborhood SCs. Areas of improvement are discussed. Trial registration : ClinicalTrials.gov NCT04440969 retrospectively registered on 22 June 2020.

Abstract Background Consideration of circulating biomarkers for risk stratification in heart failure (HF) is recommended, but the influence of atrial fibrillation (AF) on prognostic performance of many markers is unclear. We investigated the influence of AF on the prognostic performance of circulating biomarkers in HF. Methods N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide, C-type natriuretic peptide (CNP), NT-proCNP, high-sensitivity troponin-T, high-sensitivity troponin-I, mid-regional-propeptide adrenomedullin, co-peptin, growth differentiation factor-15, soluble Suppressor of Tumorigenicitiy (sST2), galectin-3, and procalcitonin plasma concentrations were measured in a prospective, multicenter study of adults with HF. AF was defined as a previous history of AF, and/or presence of AF/flutter on baseline 12-lead electrocardiogram. The primary outcome was the composite of HF-hospitalization or all-cause mortality at 2 years. Results Among 1099 patients (age 62 ± 12years, 28% female), 261(24%) patients had AF. Above-median concentrations of all biomarkers were independently associated with increased risk of the primary outcome. Significant interactions with AF were detected for galectin-3 and sST2. In considering NT-proBNP for additive risk stratification, sST2 (adjusted hazard ratio [AHR]1.85, 95%confidence interval [C.I.] 1.17-2.91) and galectin-3 (AHR1.85, 95%C.I. 1.09-2.45) were independently associated with increased primary outcome only in the presence of AF. The prognostic performance of sST2 was also stronger in AF for all-cause mortality (AF: AHR2.82, 95%C.I. 1.26-6.21; non-AF: AHR1.78, 95% C.I. 1.14-2.76 without AF), while galectin-3 predicted HF-hospitalization only in AF (AHR1.64, 95%C.I. 1.03-2.62). Conclusions AF modified the prognostic utility of selected guideline-endorsed HF-biomarkers. Application of markers for prognostic purposes in HF requires consideration of the presence or absence of AF. Clinical trial registration ACTRN12610000374066

Malnutrition is a major determinant of the physical frailty syndrome. Dynamic transitions in frailty states over time is well documented, but few studies have documented temporal changes in nutritional states and whether they influence frailty outcomes. Longitudinal cohort study. Community-dwelling older Singaporeans aged ≥55y with a 5-year follow-up (n=1162) in the Singapore Longitudinal Ageing Study 2 (SLAS-2). The Mini Nutritional Assessment Short-Form (MNA-SF) was used to determine nutritional status, and the Fried's criteria (shrinking, weakness, slowness, exhaustion and inactivity) was used to assess physical frailty phenotype at both baseline and follow-up. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were adjusted for multiple baseline co-variables. At baseline, being at risk of malnutrition/malnourished was associated with increased odds of prevalent prefrailty (OR=2.76, 95% CI=1.86-4.10) and frailty (OR=4.10, 95% CI=1.41-11.9). Baseline robust individuals who were persistently at risk of malnutrition/malnourished showed an increased odds of conversion to being pre-frail/ frail at follow-up (OR=3.45, 95% CI=1.00-11.9). Among baseline pre-frail/frail individuals, reversion to being robust were significantly less likely among those who were persistently at risk of malnutrition/malnourished (OR=0.26, 95% CI=0.10-0.67) and those whose baseline normal nutrition worsened at follow-up (OR=0.20, 95% CI=0.06-0.74). Changes in nutritional states are associated with frailty state transitions, and monitoring changes in nutritional status is recommended for the prevention and severity reduction of frailty among older people in the community.

The objective of this study is to examine ethnic differences in Mini-Mental State Examination (MMSE) test performance in discriminating between demented and nondemented elderly Asians. A nationally representative population sample (N = 1,092) of community-living elderly, comprising Chinese, Malays, and Indians in Singapore, was interviewed using MMSE, Geriatric Mental State, and demographic and health questionnaires. There were significant ethnic differences in mean MMSE scores among Chinese (26.2), Indians (25.0), and Malays (23.6), but only in noneducated subjects. No ethnic differences in MMSE were observed in higher educated subjects. The sample proportion of subjects with dementia was 4.2% in Chinese, 9.4% in Malays, and 8.8% in Indians. Overall, MMSE discriminated well between subjects with and without dementia (cutoff: 23/24, area under the curve: 95%, sensitivity: 97.5%, specificity: 75.6%). MMSE test performance was much better in higher educated subjects (higher specificity: 85.2%). Lower specificities were shown in less educated subjects (57.3%), and in Malays (62.8%), and especially in less educated Malays (35.3%) and Indians (50.0%). Significant differences in MMSE scores in less educated subjects persisted after adjusting for differences in sociodemographic, health, and behavioral variables Ethnic nonequivalence in MMSE test performance should be taken into account in dementia screening in Asians in less educated subjects. Known correlates of cognitive functioning did not sufficiently explain these differences.

Elevated homocysteine has emerged as a risk factor for cognitive impairment even in healthy elderly persons. Reduced brain volume and white matter hyperintensities also occur in healthy elderly as well, but the interrelationships between these have not been well studied. We report these interrelationships in non demented, relatively healthy, community-dwelling older adults from a single East Asian population. Two hundred twenty-eight right-handed participants age 55 years and above were evaluated. Persons with medical conditions or neurological diseases other than well-controlled diabetes mellitus and hypertension were excluded. Participants underwent quantitative magnetic resonance imaging of the brain using a standardized protocol and neuropsychological evaluation. Plasma homocysteine, folate, vitamin B12, and markers for cardiovascular risk: blood pressure, body mass index, fasting blood glucose, and lipid profile were measured. Elevated homocysteine was associated with reduced global cerebral volume, larger ventricles, reduced cerebral white matter volume, and lower cognitive performance in several domains. Elevated homocysteine was associated with reduced white matter volume (β = −20.80, t = −2.9, df = 223, p = 0.004) and lower speed of processing (β = −0.38, t = −2.1, df = 223, p = 0.03), even after controlling for age, gender, and education. However, the association between homocysteine and lower speed of processing disappeared after controlling for white matter volume. Elevated homocysteine was not associated with white matter hyperintensity volume or with hippocampal volume. Although homocysteine and folate levels were correlated, their effects on white matter volume were dissociated. In non demented, relatively healthy adults, elevated homocysteine is associated with lower cognitive scores and reduced cerebral white matter volume. These effects can be dissociated from those related to white matter hyperintensities or reduced folate level.

Objective No previous studies have empirically demonstrated a multiplicative interactive effect of anxiety disorders and/or depression (ADD) and chronic medical conditions on quality of life (QOL). We hypothesized that QOL impairment was worsened by the presence of ADD and medical co-morbidity, more than when it was with either medical co-morbidity alone or ADD alone. Methods Complete data of 2,801 participants from the National Mental Health Survey of Adults in Singapore were analyzed, using SCAN diagnoses of anxiety disorders and depression, self-reports of chronic medical conditions, and SF-12 measures of QOL (Mental Component Summary, MCS, and Physical Component Summary, PCS). Results Persons diagnosed with ADD (compared to those without) had considerably more medical co-morbidities (59 vs. 33%, p  < 0.001). In multiple regression analyses, ADD (vs. no ADD) was associated with lower PCS ( b  = −1.013, p  = 0.045) and MCS scores ( b  = −9.912, p  < 0.001), as was number of medical co-morbidities (0, 1–2, 3 +), PCS scores ( b  = −2.058, p  < 0.001) and MCS scores ( b  = −1.138, p  < 0.001). There were significant interactive effects of medical co-morbidities and ADD on PCS ( p  < 0.001), and MCS ( p  = 0.086), suggesting that the negative effects of medical conditions on quality of life was aggravated non-additively by the co-morbid presence of ADD, and vice versa. Conclusion The individual effects of medical and psychiatric morbidity on functional status and quality of life were considerably worse when both were present in the same individual. Future studies should examine the impact of identifying and treating anxiety and depressive disorders in patients with medical problems for better outcomes.

Most studies of successful aging have used restricted definitions based on the absence of disability and identified a small number of predictors. The authors aimed to examine whether a broad multidimensional definition of successful aging has good construct validity and identified a wider range of predictors that are relevant for multifaceted interventions. Cross-sectional and longitudinal data analyses were performed on 1,281 community-living Chinese elderly of 65 years and above in the Singapore Longitudinal Aging Study cohort. Successful aging was measured in multiple dimensions of functioning and wellness: cognitive and affective status, physical health, social functioning and engagement and life satisfaction, and a summary composite measure created across dimensions to form a dichotomous variable. Potential determinants included sociodemographic, psychosocial, behavioral variables. Successful aging was determined in 28.6% of respondents and in multivariate models was significantly (p <0.05) associated with age (OR = 0.90), female gender (OR = 1.37), ≥6 years of education (OR = 2.31), better housing (OR = 1.41), religious or spiritual beliefs (OR = 1.64), physical activities and exercise (OR = 1.90), and low or no nutritional risk (OR = 2.16). In contrast to findings based on more restricted biomedical definitions of successful aging, a multidimensional definition of successful aging identified more variables including demographic status, psychosocial support, spirituality, and nutrition as salient determinants.

A population cohort of 5015 participants aged 55 years and above free of CVD at baseline was followed for up to 10 years. Pre-frailty and frailty were defined as the presence of 1-2 and 3-5 modified Fried criteria (unintentional weight loss, weakness, slow gait speed, exhaustion, and low physical activity), incident CVD events as newly diagnosed registered cases of myocardial infarction (MI), stroke, and CVD-related mortality (ICD 9: 390 to 459 or ICD-10: I00 to I99). Covariate measures included traditional cardio-metabolic and vascular risk factors, medication therapies, Geriatric Depression Scale (GDS), Mini-Mental State Exam (MMSE), and blood biomarkers (haemoglobin, albumin, white blood cell counts and creatinine). Pre-frailty and frailty were significantly associated with elevated HR = 1.26 (95%CI: 1.02-1.56) and HR = 1.54 (95%CI:1.00-2.35) of overall CVD, adjusted for cardio-metabolic and vascular risk factors and medication therapies, but not after adjustment for GDS depression and MMSE cognitive impairment. The HR of association between frailty status and both CVD mortality and overall mortality, however, remained significantly elevated after full adjustment for depression, cognitive and blood biomarkers. Frailty was associated with increased risk of CVD morbidity and especially mortality, mediated in parts by traditional cardio-metabolic and vascular risk factors, and co-morbid depression and associated cognitive impairment and chronic inflammation. Given that pre-frailty and frailty are reversible by multi-domain lifestyle and health interventions, there is potential benefits in reducing cardiovascular diseases burden and mortality from interventions targeting pre-frailty and early frailty population.

Background: Studies report varying rates and predictors of mild cognitive impairment (MCI) progression and reversion. Methods: We determined MCI reversion and progression among 473 community-living adults aged ≥55 years in the Singapore Longitudinal Ageing Study with an average of 6 years of follow-up and estimated association with baseline variables. Results: A total of 208 MCI participants reverted to normal cognition (44.0%) and 19 progressed to dementia (4.0%). In a model adjusted for age, gender, education, ethnicity, cardiovascular risk factors/diseases, APOE ε4 status, depressive symptoms, leisure-time activities (LTA), and baseline Mini-Mental State Examination (MMSE), we found that LTA score (OR = 1.07, 95% CI 1.02–1.13), MMSE score (OR = 1.21, 95% CI 1.11–1.31), and subjective memory complaint (OR = 1.83, 95% CI 1.16–2.90) significantly predicted MCI reversion. Controlling for all variables, age (OR = 1.09, 95% CI 1.02–1.17), lower education (OR = 3.26, 95% CI 1.01–10.49), and the metabolic syndrome (OR = 3.13, 95% CI 1.12–8.77) significantly predicted MCI progression. Controlling for age, sex, ethnicity, and education, diabetes significantly predicted MCI progression (OR = 3.19, 95% CI 1.23–8.26), but the presence of other cardiometabolic factors reduced this association to an OR of 2.18 (95% CI 0.72–6.60). Conclusion: In this relatively younger population, there were higher rates of MCI reversion and lower rates of MCI progression which were predicted by the positive effects of LTA and a higher MMSE score as well as by the deleterious effect of the metabolic syndrome and diabetes.

Human primary monocytes comprise a heterogeneous population that can be classified into three subsets based on CD14 and CD16 expression: classical (CD14 high /CD16 − ), intermediate (CD14 high /CD16 + ), and non-classical (CD14 low /CD16 + ). The non-classical monocytes are the most pro-inflammatory in response to TLR stimulation in vitro , yet they express a remarkably high basal level of miR-146a, a microRNA known to negatively regulate the TLR pathway. This concurrence of a pro-inflammatory status and a high miR-146a level has been associated with cellular senescence in other cell types. Hence, we assessed the three monocyte subsets for evidence of senescence, including proliferative status, telomere length, cellular ROS levels, and mitochondrial membrane potential. Indeed, the non-classical subset exhibited the clearest hallmarks of senescence, followed by the intermediate and then the classical subset. In addition, the non-classical subset secreted pro-inflammatory cytokines basally in vitro . The highly pro-inflammatory nature of the non-classical monocytes could be a manifestation of the senescence-associated secretory phenotype (SASP), likely induced by a high basal NF-κB activity and IL-1α production. Finally, we observed an accumulation of the non-classical monocytes, in conjunction with higher levels of plasma TNF-α and IL-8, in the elderly. These factors may contribute to inflamm-aging and age-related inflammatory conditions, such as atherosclerosis and osteoarthritis. With our new understanding that the non-classical monocyte subset is a senescent population, we can now re-examine the role of this subset in disease conditions where this subset expands.