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Background: With lean mass declining early in Alzheimer's disease, muscle quality beyond quantity is relevant to physical performance. We sought to identify potentially modifiable factors for the differential loss of muscle mass (pre-sarcopenia) and its performance (sarcopenia) in older adults with mild cognitive impairment (MCI) and mild-to-moderate Alzheimer's disease (AD)., Methods: This is a cross-sectional study of 108 community-dwelling older adults with MCI and mild-to-moderate AD. Participants were categorized as: (i) No sarcopenia (normal muscle mass), (ii) Pre-sarcopenia (low muscle mass without weakness or slowness), (iii) Sarcopenia (low muscle mass AND weak grip strength and/or slow gait speed) using Asian cut-offs. Muscle quality was defined as the ratio of grip and knee extension strength to average arm and leg lean mass respectively. We measured cognitive, functional and physical (Short Physical Performance Battery, SPPB) performance; physical activity level; nutritional status; and blood biomarkers of inflammation and endocrine dysfunction., Results: SPPB (p=0.033) and activity level (p=0.010) were highest in the pre-sarcopenic group. Pre-sarcopenic group had highest arm muscle quality [10.6 (7.7-12.2) vs 13.9 (12.6-15.7) vs 11.3 (9.7-12.8), p<0.001], despite significantly lower appendicular lean mass than non-sarcopenic group. In multi-nomial logistic regression reference to non-sarcopenic group, malnutrition independently increased risk for both pre-sarcopenia (Relative risk=7.53, 95% C.I 1.20-47.51, p=0.032) and sarcopenia (Relative risk=11.91, 95% C.I 2.85-49.77, p=0.001). A combined pro-inflammatory and endocrine deficient state significantly increased the risk of sarcopenia (Relative risk=5.17, 95% C.I 1.31-20.37, p=0.019)., Conclusion: Malnutrition is a precursor for progressive loss of muscle mass, but a pro-inflammatory and endocrine deficient state may potentially aggravate decline in muscle quality to culminate in frank sarcopenia., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Frailty and intrinsic capacity (IC) are distinct but interrelated constructs. Uncertainty remains regarding how they are related and interact to influence health outcomes. We aim to understand the relationship between frailty and IC by identifying subgroups based on frailty criteria and IC domains and studying one-year outcomes. Methods: We studied 200 independent community-dwelling older adults (mean age 67.9±7.9 years, Modified Barthel Index (MBI) score 99±2.6). Frailty was defined by modified Fried criteria. Scores (range: 0–2) were assigned to individual IC domains (cognition, psychological, locomotion, and vitality) to yield a total IC score of 8. To identify subgroups, two-step cluster analysis was performed with age, frailty and IC domains. Cluster associations with one-year outcomes (frailty, muscle strength (grip strength, repeated chair stand test), physical performance (gait speed, Short Physical Performance Battery), function (MBI) and quality-of-life (EuroQol (EQ)-5D)) were examined using multiple linear regression adjusted for age, gender and education. Results: Three distinct clusters were identified — Cluster 1: High IC/Robust (N=74, 37%); Cluster 2: Intermediate IC/Prefrail (N=73, 36.5%); and Cluster 3: Low IC/Prefrail-Frail (53, 26.5%). Comparing between clusters, IC domains, cognition, depressive symptoms, nutrition, strength and physical performance were least impaired in Cluster 1, intermediate in Cluster 2 and most impaired in Cluster 3. At one year, the proportion transitioning to frailty or remaining frail was highest in Cluster 3 compared to Cluster 2 and Cluster 1 (39% vs 6.9% vs 2.8%, P<0.001). Compared to Cluster 1, Cluster 3 experienced greatest declines in grip strength (β=−4.1, P<.001), MBI (β=−1.24, P=0.045) and EQ-5D utility scores (β=−0.053, P=0.005), with Cluster 2 intermediate between Cluster 1 and Cluster 3. Conclusions: Amongst independent community-dwelling older adults, IC is complementary to frailty measures through better risk-profiling of one-year outcomes amongst prefrail individuals into intermediate and high-risk groups. The intermediate group merits follow-up to ascertain longer-term prognosis. [ABSTRACT FROM AUTHOR]

Background: Studies suggest that nutritional interventions using the whole diet approach such as the Mediterranean diet may delay cognitive decline and dementia onset. However, substantial numbers of older adults are non-adherent to any ideally healthy dietary pattern and are at risk of malnutrition. Objective: The present study investigated the relationship between global malnutrition risk and onsets of cognitive decline and neurocognitive disorders (NCD), including mild cognitive impairment (MCI) or dementia in community-dwelling older adults. Methods: Participants aged ≥55 years in the Singapore Longitudinal Ageing Studies (SLAS) were assessed at baseline using the Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA) and followed up 3–5 years subsequently on cognitive decline (MMSE drop ≥ 2) among 3128 dementia-free individuals, and incident neurocognitive disorders (NCD) among 2640 cognitive normal individuals. Results: Individuals at high nutritional risk score (≥3) were more likely to develop cognitive decline (OR=1.42, 95%CI=1.01–1.99) and incident MCI-or-dementia (OR=1.64, 95%CI=1.03–2.59), controlling for age, sex, ethnicity, low education, APOE-e4, hearing loss, physical, social, and mental activities, depressive symptoms, smoking, alcohol, central obesity, hypertension, diabetes, low HDL, high triglyceride, cardiac disease, and stroke. Among ENIGMA component indicators, low albumin at baseline was associated with cognitive decline and incident NCD, and 5 or more drugs used, few fruits/vegetables/milk products daily, and low total cholesterol were associated with incident NCD. Conclusion: The ENIGMA measure of global malnutrition risk predicts cognitive decline and incident neurocognitive disorders, suggesting the feasibility of identifying vulnerable subpopulations of older adults for correction of malnutrition risk to prevent neurocognitive disorders. [ABSTRACT FROM AUTHOR]

Importance: Muscle strength has been elevated to the forefront of sarcopenia diagnosis, with handgrip strength the preferred measure. Extant handgrip protocols adopt different handgrip strength (HGS) criteria. Paucity of direct comparison studies assessing the impact of HGS criterion on prevalence of sarcopenia and predictive validity on physical performance contributes to the lack of standardisation of HGS criteria in sarcopenia diagnosis. Objectives: Our study aims to compare the effect of average (HGSave) versus maximum (HGSmax) HGS criterion on: (1) prevalence of low HGS and sarcopenia; and (2) association with physical performance at baseline and at 2 years. Methods: We recruited 200 community dwelling, cognitively intact, and functionally independent older adults. Muscle strength, physical performance measures, cognitive tests and nutritional assessments were performed. Short Physical Performance Battery (SPPB) was administered at baseline and at 2 years. We compared HGSave and HGSmax to assess the prevalence of low HGS and sarcopenia. Univariate analysis was performed comparing baseline characteristics between low and normal groups for each HGS criterion. Significantly different variables were included in logistic regression analysis to examine association of low HGS and SPPB at baseline. Predictive validity of low HGS for SPPB<10 at 2 years was examined by performing logistic regression analysis for HGSave and HGSmax. Results: The prevalence of low HGS and sarcopenia incorporating HGSave criterion is 40% and 33% respectively, whereas that of HGSmax criterion is 21% and 19.5% respectively. There is moderate agreement between the 2 HGS criteria for sarcopenia diagnosis (kappa=0.604) and poorer agreement for low HGS (kappa=0.570). There was no significant association with baseline SPPB for both HGS criteria. At 2 years, only low HGSmax was significantly associated with low SPPB (adjusted OR 3.91, 95% CI 1.24–12.33). Conclusion: Our study demonstrates that HGS criteria matters in diagnosis of sarcopenia and we support extant HGS protocols using HGSmax criterion in view of better predictive validity for poor physical performance. [ABSTRACT FROM AUTHOR]

Background: EWGSOP2 criteria for sarcopenia recommends the use of either handgrip strength (GS) or 5-times repeated chair stand test (RCS) as a muscle strength measure. We aim to compare the impact of different muscle strength definitions on sarcopenia prevalence and predictive validity for 2-year outcomes, using the EWGSOP2 clinical algorithm. Methods: We studied 200 community-dwelling older adults, comparing sarcopenia prevalence using three muscle strength definitions: 1) maximum GS (Asian Working Group cutoffs); 2) RCS-1 (standard cutoff >15s); and 3) RCS-2 (ROC-derived cutoff >12.5s). Two-year outcomes include: 1) Incident frailty (modified Fried criteria); 2) Physical performance [Short Physical Performance Battery (SPPB) score <10]; and 3) Quality of life [EuroQol-5 dimension (EQ-5D) <25th percentile]. We performed logistic regression on 2-year outcomes adjusted for age, gender, cognition and mood. Results: Prevalence of confirmed sarcopenia was 14.5%, 4% and 9% for GS, RCS-1 and RCS-2 respectively. For 2-year outcomes (N=183), RCS-2 predicted incident frailty (OR: 5.7, 95% CI 1.4–22.8, p=0.013), low SPPB (OR: 4.4, 95% CI 1.4–13.1, p=0.009), and trended towards predicting low QOL (OR: 2.1, 95% CI 0.9–4.9, p=0.095). In contrast, GS and RCS-1 did not predict frailty nor low QOL, but predicted low SPPB only (GS: OR 3.8, 95% CI 1.3–10.6, p=0.01; RCS-1: OR: 8.8, 95% CI 2.2–35.0, p=0.002). Conclusions: Sarcopenia prevalence varies with muscle strength definitions, with GS being significantly higher vis-á-vis RCS definitions. Our results also support the use of population-specific over standard cutoffs for RCS to obtain intermediate estimates of sarcopenia prevalence and the best predictive validity for two-year outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Asian studies on how physical tests predict short-term mortality in elderly are scarce. We assessed handgrip strength and timed-up-and-go (TUG) as such predictors among elderly Chinese in Singapore. Design: Prospective cohort study. Setting: Community-dwelling Chinese elderly in Singapore. Participants: We used data from 13,789 subjects in the prospective, population-based Singapore Chinese Health Study, who had a mean age of 74 (range 63 to 97) years at time of measurements. Measurements: Subjects underwent assessment for handgrip strength and TUG. They were followed for mortality via linkage with nationwide death registry through 2018. Results: In multivariable analyses, handgrip strength was inversely associated with risk of mortality in a dose-dependent manner: the hazard ratio (HR) [95% confidence interval (CI)] comparing extreme quartiles was 2.05 (1.44–2.90) (Ptrend<0.001). TUG was positively associated with mortality in a stepwise manner: the HR (95% CI) comparing extreme quartiles was 3.08 (2.17–4.38) (Ptrend<0.001). Compared to those with stronger handgrip and faster TUG, participants who either had weaker handgrip or slower TUG had a significant 1.59 to 2.11 fold increase in risk of mortality; while the HR (95% CI) for those who had both weaker handgrip and slower TUG was 3.93 (3.06–5.05). In time-dependent receiver operating characteristic curves, adding handgrip strength and TUG time to a Cox model containing sociodemographic and lifestyle factors, comorbidities, and body measurements significantly improved the area under the curve for the prediction of mortality from 0.5 to 2 years (P≤0.001). Conclusion: Among elderly in a Chinese population, handgrip strength and TUG test were strong and independent predictors of short-term mortality. [ABSTRACT FROM AUTHOR]

Objectives: To investigate serum myostatin (absolute and normalized for total body lean mass (TBLM)) and IGF-1 as biomarkers of frailty and low relative appendicular skeletal muscle mass (RASM) in older adults, and; to examine gender differences in the association of serum myostatin and IGF-1 levels with frailty and low RASM. Design: Cross-sectional study. Setting: The "Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and predicting frailty and functional decline in community-dwelling Asian older adults Study" (GERI-LABS) study in Singapore. Participants: 200 subjects aged 50 years and older residing in the community. Measurements: Frailty was assessed using the modified Fried criteria. Low RASM was defined using cutoffs for height-adjusted appendicular skeletal muscle mass measured by dual-energy X-ray absorptiometry as recommended by the Asian Working Group for Sarcopenia. Comorbidities, cognitive and functional performance, physical activity and nutritional status were assessed. Blood samples collected included serum myostatin, insulin-like growth factor 1 (IGF-1) and markers of inflammation (total white cell count, CRP, IL-6 and TNFaR1). Subjects were classified into 4 groups: Frail/Prefrail with low RASM (Frail/Low RASM), Frail/Prefrail with normal RASM (Frail/Normal RASM), Robust with low RASM (Robust/Low RASM) and Robust with normal RASM (Robust/Normal RASM). Results: 63 (32%) subjects were classified as Frail/Low RASM, 53 (27%) Frail/Normal RASM, 28 (14%) Robust/Low RASM and 56 (28%) Robust/Normal RASM respectively. Frail/Low RASM subjects were older and had lower BMI compared to Frail/Normal RASM and robust subjects. Mean (SE) normalized myostatin levels were higher in Frail/Low RASM compared to Frail/Normal RASM subjects (1.0 (0.04) versus 0.84 (0.05) ng/ml/kg, P=0.01). Median (IQR) IGF-1 level was lower amongst Frail/Low RASM subjects compared to Frail/Normal RASM subjects (102.3, (77.7, 102.5) vs 119.7 (82.7, 146.0) ng/ml, P=0.046). No differences in myostatin or IGF-1 were observed among robust individuals with or without low muscle mass. In adjusted multinomial logistic regression models with Robust/Normal RASM as the reference group, myostatin (P=0.05) and IGF-1 (P=0.043) were associated with Frail/Low RASM status in the whole cohort. When stratified by gender, myostatin was significantly associated with Frail/Low RASM status in men only (P=0.03). In women, serum IGF-1 was associated with Frail/Low RASM status (P=0.046), but not myostatin (P=0.53). Conclusion: Serum myostatin, normalized for TBLM in men and IGF-1 in women are potential biomarkers for frail individuals with low RASM, and may identify a target group for intervention. [ABSTRACT FROM AUTHOR]

Background: The Frontal Assessment Battery (FAB) is a reliable and valid bedside tool for testing executive function in dementia. Given the increasing interest in utility of FAB as a screening tool in early cognitive impairment (ECI), there is a surprising lack of studies evaluating its psychometric property and factor structure, nor the influence of factors such as age, education and gender, in ECI. Objectives: This study aims to investigate the psychometric properties and factor structure of FAB in older adults with ECI, as well as the influence of age, gender and education. Design, Setting and Participants: This is a retrospective, observational cross-sectional study with 300 community dwelling, predominantly Chinese older adults (14 normal, 130 mild cognitive impairment (MCI), and 156 mild dementia) who presented to Memory Clinic from January 2011 to December 2013. Measurements and Analysis: We collected data on demographic, cognitive, functional and behavioral evaluation. To examine the psychometric properties of FAB, we examined the concurrent, convergent, and discriminant validity; internal consistency by Cronbach's alpha; and factor structure by exploratory factor analysis. The influence of age, education and gender was examined using unadjusted and adjusted correlational analyses with CDR-SOB. We performed analysis for the whole group and for MCI subgroup. Results: FAB total score decreases significantly from normal to dementia group attesting to concurrent validity. It correlated significantly with digit span backwards and Chinese Mini Mental State Examination (r=0.38 and 0.47 respectively, p<0.01) and poorly with Neuropsychiatric Inventory-Questionnaire and depression (r=0.004 and −0.02 respectively), supporting its convergent and discriminant validity. Factor analysis yielded a single-factor solution for FAB with fair Internal consistency (alpha=0.610). FAB is relatively unaffected by age, gender and education level. These good psychometric properties extend to MCI, albeit with greater influence by education level. FAB items of conceptualization and mental flexibility have good discriminatory ability between MCI and normal subjects. Conclusion: FAB has good concurrent, convergent and discriminant validity with fair internal consistency in ECI that is premised on a one-factor structure. It is relatively unaffected by age, gender or education. Taken together, FAB is a useful bedside screening tool for executive function in ECI. [ABSTRACT FROM AUTHOR]

Objective: Recent studies have described worry about caregiver performance (WaP) as a distinct dimension of caregiver burden. We aimed to explore care recipient and caregiver characteristics between the concordant and discordant WaP groups in a population of caregivers of older adults with cognitive impairment. The secondary objective is to explore if there are differences between high and low WaP subsets in the 'doing more' and 'doing better' groups. Design, setting and participants: This is a retrospective study of 936 dyads of community-dwelling older adults with cognitive complaints and their primary family caregiver from a hospital in Singapore. Measurements: We performed descriptive and inferential statistics of the characteristics of caregivers and patients. We categorized caregiver-patient dyads into four groups, namely concordant (high vs low WaP) and discordant ('doing more' vs 'doing better') groups. For both concordant and discordant groups, we further defined low and high WaP subgroups using tertile cutoffs. Results: The concordant low WaP group is predicted by the spousal relationship (p<.001) and care recipients with fewer neuropsychiatric symptoms (p<.001). There is no significant difference between the discordant groups, which were predominantly the adult children. Further analysis of subgroups found that in the 'doing better' group, there were more spouses in the high as compared to low WaP subgroups, with the reverse true in the 'doing more' group. In the 'doing more' group, caregivers with high WaP also had higher total ZBI (p<0.05) with higher factors (Fl, F2 and F3) scores (p<0.05). They also endorsed higher NPI-Q scores (p=0.045) particularly in the domain of depression / dysphoria (p=0.034). These differences are not seen in the 'doing better' group. Conclusion: Our study suggests an association with caregiver characteristics (adult child) and disruptive behavior in the 'do more' high WaP discordant group. Delineating into the high and low WaP subgroups can help us identify the 'do more' high WaP subgroup that merits further attention and early intervention. [ABSTRACT FROM AUTHOR]

Background: Depression is prevalent among patients with late life neurocognitive disorders but its role as an independent risk factor is not established. We aimed to examine the longitudinal relationship between depression and the incidence of mild neurocognitive disorders (NCD) in a Chinese population. Methods: We analyzed data from 889 community-living Chinese elderly in the Singapore Longitudinal Aging Study (SLAS) cohort. All subjects were cognitively normal at baseline based on their performance on the Mini-Mental State Examination (MMSE). Depression was defined as total score of 5 or more on the 15-item Geriatric Depression Scale. Incident cases of mild NCD were ascertained at follow up after an average of 45 moths (range: 10-62). Odds ratios (OR) of associations were calculated in logistic regression models that adjusted for potential confounders. Results: A total of 59 mild NCD cases were identified. Increased risk of mild NCD was observed for subjects who had depressive symptom at baseline (OR=2.56, 95%CI 1.17-5.60) after controlling for age, gender, education, hypertension, diabetes mellitus, heart disease, APOE genotype and length of follow-up. The interaction between depression and APOE genotype was not statistically significant. Conclusion: Depressive symptom was independently associated with increased risk of mild NCD among Chinese elderly. Effective management of late life depression may potentially reduce incident cases of NCD in the population. [ABSTRACT FROM AUTHOR]