Dose-Responsive Impacts of Social Frailty on Intrinsic Capacity and Healthy Aging among Community-Dwelling Middle-aged and Older Adults: Stronger Roles of Social Determinants over Biomarkers.

OBJECTIVE: The intricate relationship between social determinants, e.g., social frailty, biomarkers and healthy aging remains largely unexplored, despite the potential for social frailty to impact both intrinsic capacity (IC) and functional ability in the aging process. DESIGN: Retrospective longitudinal cohort study. SETTING AND PARTICIPANTS: Participants aged 50+ years from the Social Environment and Biomarkers of Aging Study (SEBAS) in Taiwan, stratified into three age groups: 50-64, 65-74 and 75+. MEASUREMENTS: Social frailty was defined based on a score derived from four domains: exclusion from general resources, social resources, social activity, and fulfillment of basic social needs. The scores were categorized as score=0 (no social frailty), 1 (social pre-frailty), and 2+ (social frailty). Multivariable logistic regression and Cox proportional hazard models were employed to examine the dose-responsive relationship between social frailty, low IC, functional and psychological health, and mortality. RESULTS: Of 1015 study participants, 24.9% and 7.9% were classified as social pre-frailty and social frailty, respectively. No significant differences were observed in most biomarkers between those with social frailty and those without. A dose-responsive relationship was found between social frailty and increased risk of low IC (social pre-frailty: aOR 2.20 [95% CI 1.59-3.04]; social frailty: 5.73 [3.39-9.69]). Similar results were found for functional and psychological health. However, no significant association between social frailty and all-cause mortality was found at the 4-year follow-up (social pre-frailty: aHR 1.52 [95% CI 0.94-2.43]; social frailty: 1.59 [0.81-3.09]). CONCLUSIONS: The significant association between social frailty and low IC, functional limitations, cognitive declines, and depressive symptoms underscores the pressing need for research on intervention strategies to enhance healthy aging in the lifespan course.

Roles of Baseline Intrinsic Capacity and its Subdomains on the Overall Efficacy of Multidomain Intervention in Promoting Healthy Aging among Community-Dwelling Older Adults: Analysis from a Nationwide Cluster-Randomized Controlled Trial.

BACKGROUND: Impaired intrinsic capacity (IC), which affects approximately 90% of older adults, is associated with a significantly heightened risk of frailty and cognitive decline. Existing evidence suggests that multidomain interventions have the potential to enhance cognitive performance and yield positive effects on physical frailty. OBJECTIVE: To examine roles of baseline IC and its subdomains on the efficacy of multidomain interventions in promoting healthy aging in older adults. DESIGN: a cluster-randomized controlled trial. SETTING AND PARTICIPANTS: 1,054 community-dwelling older adults from 40 community-based clusters across Taiwan. INTERVENTION: A 12-month pragmatic multidomain intervention of exercise, cognitive training, nutritional counseling and chronic condition management. MEASUREMENTS: Baseline IC was measured by 5 subdomains, including cognition (Montreal Cognitive Assessment, MoCA), sensory (visual and hearing impairment), vitality (handgrip strength or Mini-Nutritional Assessment-short form), psychological well-being (Geriatric Depression Scale-5), and locomotion (6m gait speed). Outcomes of interest were cognitive performance (MoCA scores) and physical frailty (CHS frailty score) over a follow-up period of 6 and 12 months. RESULTS: Of all participants (mean age:75.1±6.4 years, 68.6% female), about 90% participants had IC impairment at baseline (2.0±1.2 subdomains). After covariate adjustment using a generalized linear mixed model (GLMM), the multidomain intervention significantly prevented cognitive declines and physical frailty, particularly in those with IC impairment ≥ 3 subdomains (MoCA: coefficient: 1.909, 95% CI: 0.736 ~ 3.083; CHS frailty scores: coefficient = -0.405, 95% CI: -0.715 ~ -0.095). To assess the associations between baseline poor capacity in each IC subdomain and MoCA/CHS frailty scores over follow-up, a 3-way interaction terms (time*intervention*each poorer IC subdomains) were added to GLMM models. Significant improvements in MoCA scores were shown for participants with poorer baseline cognition (coefficient= 1.138, 95% CI: 0.080 ~ 2.195) and vitality domains (coefficient= 1.651, 95% CI: 0.541 ~ 2.760). The poor vitality domain also had a significant modulating effect on the reduction of CHS frailty score after the 6- and 12-month intervention period (6 months: coefficient= -0.311, 95% CI: -0.554 ~ -0.068; 12 months: coefficient= -0.257, 95% CI: -0.513 ~ -0.001). CONCLUSION AND IMPLICATIONS: A multidomain intervention in community-dwelling older adults improves cognitive decline and physical frailty, with its effectiveness influenced by baseline IC, highlighting the importance of personalized strategies for healthy aging.

Age- and Sex-Different Associations between Cognitive Performance and Inflammatory Biomarkers in Community Dwelling Older Adults: towards Precision Preventive Strategies.

BACKGROUND: Studies have demonstrated associations between inflammatory biomarkers and cognitive function in people with dementia or stroke, but little is known regarding these associations in healthy middle-aged and older populations. OBJECTIVES: This study aims to examine associations between inflammatory biomarkers (both vascular and systemic) and cognitive performance in stroke- and dementia-free middle-aged and older adults without apolipoprotein E4 (ApoE ε4) allele carriers. DESIGN: A cross-sectional study. SETTING: Social Environment and Biomarkers of Aging Study (SEBAS) 2006. PARTICIPANTS: A total of 983 participants aged 53 years and older. MEASUREMENTS: Composite cognitive function assessment, including the Short Portable Mental Status Questionnaire, the Rey Auditory Verbal Learning Test, and the Wechsler Adult Intelligence Scale. Overnight venous blood sampling for 6 inflammatory biomarkers (C-reactive protein, interleukin-6, fibrinogen, homocysteine, intercellular adhesion molecule-1 and E-selectin) and ApoE genotyping. RESULTS: Among 983 participants (mean age: 65.8±9.5 years), 808 were non-ApoE e4 allele carriers and were stroke- and dementia-free. Higher log fibrinogen was associated with poorer cognitive function after adjustment for potential confounding factors in non-ApoE e4 allele carriers and stroke- and dementia-free populations (unstandardized coefficients ß= -1.553, P value= 0.003). In participants aged 65 years or older, both of elevated fibrinogen and homocysteine were associated with poorer cognitive function (ß= -2.288, P value= 0.015; ß= -1.331, P value= 0.012, respectively). Elevated log CRP was significantly associated with lower cognitive function only in women (ß= -0.514, P value= 0.024). CONCLUSION: Higher serum levels of fibrinogen were negatively associated with cognitive function, which was independent of ApoE genotyping and prior cerebrovascular events in dementia-free community-dwelling older adults. Further studies are needed to validate the roles of fibrinogen in the pathophysiology of dementia and elucidate the underlying mechanisms.

Long-Term Mortality Risk in Older Adults with Sarcopenia: An 11-Year Prospective Cohort Study Comparing AWGS 2014 and AWGS 2019 Guidelines for Enhanced Clinical Utility and Accurate Risk Prediction.

OBJECTIVES: To discern the diagnostic accuracy between the updated diagnostic consensus of the Asian Working Group for Sarcopenia (AWGS) in 2019 (AWGS 2019) and the previous AWGS 2014 guidelines. DESIGN: A prospective population-based cohort study. SETTING AND PARTICIPANTS: The study included 731 older community-dwelling adults aged ≥ 65 years who participated in face-to-face interviews and were followed up for 11-year mortality until 31 Mar 2022. MEASUREMENTS: We utilized a handgrip strength dynamometer to measure participants' muscle strength, while their walking speed was determined by a timed 6-meter walk test at their usual pace. Additionally, muscle mass was measured using dual-energy X-ray absorptiometry scanning. Sarcopenia was defined as the presence of low muscle mass in combination with weakness and/or slowness both by AWGS 2014 and 2019 criteria. RESULTS: The present study followed 731 participants (mean age 73.4 ± 5.4 years, men predominant 52.8%) over a period of 11 years, yielding 5927 person-years and 159 deaths. Prevalence of sarcopenia defined by AWGS 2019 and 2014 criteria were 8.5% and 6.8%, respectively. Sarcopenia defined by AWGS 2019 (HR 1.62, 95% CI 1.04-2.54, p=0.034) but not AWGS 2014 was significantly associated with mortality in community-living older adults after adjusting for potential confounders such as age, sex, education, drinking, disease burden and serum level of testosterone. The study also found that the AWGS 2019 criteria had a better model fitness than AWGS 2014 criteria in predicting mortality. CONCLUSION: AWGS 2019 criteria outperformed AWGS 2014 in identifying sarcopenia risk and predicting mortality. Screening for sarcopenia in older adults may improve health outcomes by identifying those at increased mortality risk.

Comparative Analysis of Intrinsic Capacity Impairments, Determinants, and Clinical Consequences in Older Community-Dwellers in Japan and Taiwan: Longitudinal Studies Showing Shared Traits and Distinct Presentations.

OBJECTIVES: Despite the recognized impact of intrinsic capacity (IC) impairment on healthy aging, international comparisons in different sociocultural contexts are scarce. This study aimed to compare IC impairment among community-dwelling older adults in Japan and Taiwan to explore the context of healthy aging in different countries. DESIGN: Comparative observational study. SETTING: National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) in Japan and Longitudinal Aging Study of Taipei (LAST) in Taiwan. PARTICIPANTS: 794 individuals (age range, 60.0-86.5 years) from NILS-LSA and 1,358 (60.0-96.7 years) from LAST. MEASUREMENTS: IC impairment was evaluated across the domains of locomotion, cognition, vitality, sensory capacity, and psychological well-being. Participants were categorized as having impaired IC or healthy. We investigated associations between IC impairment, falls, and all-cause mortality. RESULTS: IC impairment was present in 54.9% and 37.3% of participants in the NILS-LSA and LAST cohorts, respectively. Male NILS-LSA participants with impaired IC (odds ratio [OR]:1.50, 95% confidence interval [CI]:1.03-2.20), with hearing loss (OR:1.98, 95% CI:1.00-3.90) were more likely to fall. In LAST, impaired locomotion (OR:2.14, 95% CI:1.46-3.14) increased the risk of falls. Men with impaired IC (hazard ratio [HR]; 2.14, 95% CI:1.10-4.15) and visual impairment (HR:2.21, 95% CI:1.15-4.25) and women with impaired psychological well-being (HR:4.94, 95% CI:1.28-18.97) in the NILS-LSA cohort had greater risk for all-cause mortality; however, this was not shown for LAST participants. CONCLUSION: The prevalence and distribution of IC impairment and associated biomarkers differed significantly between participants in Japan and Taiwan. However, the associations with adverse outcomes remained similar, emphasizing the need for tailored interventions for healthy aging.

Cardiovascular Disease Risk Burden, Cognitive Impairments and Incident Dementia among Community-Dwelling Middle-Aged and Older Adults: An 8-Year Longitudinal Follow-up Study.

OBJECTIVES: To evaluate the associations between cardiovascular disease (CVD) risk burden (estimated by the World Health Organization (WHO) algorithm) and cognitive impairments (e.g., incident dementia, global and domain-specific impairments) among CVD-, dementia- and disability-free, community-dwelling middle-aged and older adults during an 8-year follow-up. DESIGN: A community-based longitudinal cohort study. SETTING: Yuanshan township in Yi-Lan County, Taiwan. PARTICIPANTS: A total of 889 community-dwelling residents aged 50 years or older. MEASUREMENTS: Age, sex, educational level, employment status, alcohol status, body mass index, physical activity, gait speed, depressive symptoms, WHO region-specific CVD risk scores (10-year CV risk, low: <10% vs. moderate-to-high: ≥ 10%), Chinese version of the Mini-Mental State Examination (MMSE), verbal memory by the delay-free recall in the Chinese Version Verbal Learning Test (CVVLT), language function by the Boston Naming Test and the category (animal) Verbal Fluency Test, visuospatial function by the Taylor Complex Figure Test, executive function by the digit backward and the Clock Drawing Test. RESULTS: Compared to those with low CVD risk, middle-aged and older adults with moderate-to-high CVD risk were at greater risk for cognitive impairments with respect to the MMSE (adjusted odds ratio (aOR) 1.60 [95% confidence interval (CI) 1.19-2.15], P=0.002), verbal memory (aOR 1.97 [1.43-2.70], P< 0.001) and language (aOR 1.99 [1.46-2.70], P< 0.001), as well as incident dementia (aOR 2.40 [1.33-4.33], P=0.004). After adjusting for all covariates, CVD risk was not associated with other domains of cognitive impairment. CONCLUSIONS: Among healthy, community-dwelling, middle-aged and older adults, those with moderate-to-high cardiovascular risk burden were significantly associated with incident dementia and global and domain-specific cognitive impairments (verbal memory and language), which suggests the existence of a relationship between early cognitive deficits and CVD risk burden. Further studies are needed to elucidate the pathophysiological mechanism of the link between CVD risk burden and cognitive impairment.

Clinical Efficacy of Multidomain Interventions among Multimorbid Older People Stratified by the Status of Physio-Cognitive Declines: A Secondary Analysis from the Randomized Controlled Trial for Healthy Aging.

OBJECTIVES: To investigate the clinical efficacy of integrated multidomain intervention among community-living older adults with multimorbidity and physio-cognitive decline syndrome (PCDS). DESIGN, SETTING AND PARTICIPANTS: This is the secondary analysis from a randomized controlled trial that data of 340 participants with Montreal Cognitive Assessment (MoCA) scores≥18 were excerpted for analysis. INTERVENTION: Sixteen 2-hour sessions per year were provided for participants, including physical exercise, cognitive training, dietician education and individualized integrated care for multimorbidity. MEASUREMENTS: Handgrip strength, 6-m walking speed, MoCA (total score and sub-domains), Cardiovascular Health Study (CHS) frailty score, quality of life, and serum biochemistry biomarkers. RESULTS: Overall, 96/340 (28.2%) of all participants have PCDS, and the integrated multidomain intervention significantly improved global cognitive performance (overall difference 1.1, 95% CI 0.4 - 1.8, p=0.003), and domains of concentration (overall difference 0.3, 95%CI 0.1 - 0.5, p=0.011), language (overall difference 0.2, 95%CI 0.1 - 0.3, p=0.006), abstract thinking (overall difference 0.1, 95%CI 0.0 - 0.3, p=0.027), and orientation(overall difference 0.2, 95%CI 0.0 - 0.4, p=0.013) across all timepoints among those with PCDS. Besides, interventions also significantly reduced frailty score among those with cognitive impairment no dementia (overall difference -0.3, 95%CI -0.5 - -0.1, p=0.011) and mobility impairment no disability (overall difference -0.3, 95%CI -0.4 - -0.1, p=0.004). and improved quality of life at domain of physical role limitation among those with PCDS (overall difference 5.3, 95%CI 0.3 - 10.4, p=0.038). CONCLUSIONS: The integrated multidomain lifestyle intervention plus multimorbidity management significantly improved cognitive function, and enhanced quality of life among older adults with multimorbidity and PCDS in the communities.

Intrinsic Capacity Impairment Patterns and their Associations with Unfavorable Medication Utilization: A Nationwide Population-Based Study of 37,993 Community-Dwelling Older Adults.

OBJECTIVES: Our aim was to explore the patterns of intrinsic capacity (IC) impairments among community-dwelling older adults and the associations of these different patterns with excessive polypharmacy, potentially inappropriate medications, and adverse drug reactions in a nationwide population-based study. DESIGN: A cross-sectional study included older adults from the Taiwan Integrated Care for Older People (ICOPE) program in 2020. SETTING AND PARTICIPANTS: The study subjects comprised 38,308 adults aged 65 years and older who participated in the ICOPE Step 1 screening and assessed six domains of IC following the World Health Organization (WHO) ICOPE approach. METHODS: Latent class analysis was adopted to identify distinct subgroups with different IC impairments patterns. The associations between different IC impairments patterns and unfavorable medication utilization, including excess polypharmacy (EPP), potentially inappropriate medications (PIMs), and adverse drug reactions (ADRs), were assessed by multivariate logistic regression models. RESULTS: Latent class analysis identified five distinct subgroups with different IC impairment patterns: robust (latent class prevalence: 59.4%), visual impairment (17.7%), physio-cognitive decline (PCD) with sensory impairment (12.3%), depression with cognitive impairment (7.7%), and impairments in all domains (2.9%). Compared to the robust group, all other groups were at higher odds for unfavorable medication utilization. The "depression with cognitive impairment" group (EPP: aOR=4.35, 95% CI 3.52-5.39, p<0.01; PIMs: aOR=2.73, 95% CI 2.46-3.02, p<0.01) and the "impairment in all domains" group (EPP: aOR=9.02, 95% CI 7.16-11.37, p<0.01; PIMs: aOR=3.75, 95% CI 3.24-4.34, p<0.01) remained at higher odds for EPP and PIMs after adjustment. CONCLUSIONS: We identified five distinct impairment patterns of IC, and each impairment pattern, particularly the "depression with cognitive impairment" and "impairment in all domains", was associated with higher odds of EPP and PIMs. Further longitudinal and intervention studies are needed to explore long-term outcomes of different impairment pattern and their reversibility.

Oral Nutritional Supplement with ß-hydroxy-ß-methylbutyrate (HMB) Improves Nutrition, Physical Performance and Ameliorates Intramuscular Adiposity in Pre-Frail Older Adults: A Randomized Controlled Trial.

OBJECTIVES: Supplementation of high protein oral nutrition shakes supplemented with ß-hydroxy-ß-methylbutyrate (HP-HMB) has been shown to improve muscle mass, muscle strength, and physical performance in older adults, but the roles of HP-HMB supplementation on the intramuscular adiposity remained unknown. This 12-week randomized controlled trial evaluated the changes of muscle mass, muscle strength, physical performance and intramuscular adiposity among community-dwelling pre-frail older persons. METHODS: This was an open-label, parallel group, randomized controlled trail that enrolled 70 community-dwelling pre-frail older persons without active or uncontrolled conditions, disability or dementia. The intervention group was provided with two services of HP HMB (Ensure® Plus Advance containing 3g HMB) per day for 12 weeks, and the control group was provided with professional nutritional counselling for sufficient protein intake. All participants received functional assessments, laboratory tests and magnetic resonance imaging (MRI) of the dominant leg before and after study. Intramuscular adipose tissue (IMAT) and the mid-thigh cross-sectional area (CSA) of muscle were obtained by MRI, and the IMAT-to-CSA ratio was calculated to evaluate intramuscular adiposity. RESULTS: Overall, 62 participants (mean age: 71.1±3.8 years, 69.4% female) completed the study (HP-HMB group: 29, control group: 33) and comparisons of baseline characteristics between groups were not statistically different. For the primary outcome, HP-HMB group showed significant improvements in the CSA of mid-thigh muscle (mean increase of CSA: 149.1±272.3 for HMB group vs -22.9±309.1 mm2 for control group, P=0.045). The improvement of MNA-SF was borderline (0.28±0.75 vs. -0.15±0.94, P=0.064), but serum levels of Vit D were significantly increased in the HMB group (3.83±8.18 vs. -1.30±4.81 ng/mL, P=0.002). Moreover, the body weight and BMI were significantly increased in the HMB group (1.10±1.18 vs. 0.24±1.13 kg, P=0.005; 0.56±0.68 vs. 0.22±0.47 kg/m2, P=0.019). In particular, the IMAT-to-CSA ratio was reduced in the HMB group (-0.38±1.21 vs. -0.02±2.56 %, P=0.06). Using the generalized estimating equation, we found that SPPB score in chair rise test was significantly improved (ß=0.71, 95% C.I.0.09-1.33, P=0.026). CONCLUSIONS: The 12-week supplementation with high protein oral nutrition shake supplemented with 3g HMB per day significantly increased muscle mass, as well as nutritional status and physical performance, and ameliorated the intramuscular adiposity of pre-frail older persons. Further study is needed to explore the long-term benefits of HP-HMB supplementation on muscle and metabolic health for older adults.

Physio-Cognitive Decline Syndrome as the Phenotype and Treatment Target of Unhealthy Aging.

In this era of unprecedented longevity, healthy aging is an important public health priority. Avoiding or shortening the period of disability or dementia before death is critical to achieving the defining objectives of healthy aging, namely to develop and maintain functional capabilities that enable wellbeing in older age. The first step is to identify people who are at risk and then to implement effective primary interventions. Geriatricians have identified a distinct clinical phenotype of concurrent physical frailty and cognitive impairment, which predicts high risk of incident dementia and disability and is potentially reversible. Differing operational definitions for this phenotype include "cognitive frailty", "motoric cognitive risk syndrome" and the recently proposed "physio-cognitive decline syndrome (PCDS)". PCDS is defined as concurrent mobility impairment no disability (MIND: slow gait or/and weak handgrip) and cognitive impairment no dementia (CIND: ≥1.5 SD below the mean for age-, sex-, and education-matched norms in any cognitive domain but without dementia). By these criteria, PCDS has a prevalence of 10-15% among community-dwelling older persons without dementia or disability, who are at increased risk for incident disability (HR 3.9, 95% CI 3.0-5.1), incident dementia (HR 3.4, 95% CI 2.4-5.0) and all-cause mortality (HR 6.7, 95% CI 1.8-26.1). Moreover, PCDS is associated with characteristic neuroanatomic changes in the cerebellum and hippocampus, and their neurocircuitry, which are distinct from neuroimaging features in normal aging and common dementia syndromes. Basic research and longitudinal clinical studies also implicate a hypothetical muscle-brain axis in the pathoetiology of PCDS. Most important, community-dwelling elders with PCDS who participated in a multidomain intervention had significant improvements in global cognitive function, and especially in the subdomains of naming and concentration. Our proposed operational definition of PCDS successfully identifies an appreciable population of at-risk older people, establishes a distinct phenotype with an apparently unique pathoetiology, and is potentially reversible. We now need further studies to elucidate the pathophysiology of PCDS, to validate neuroimaging features and muscle-secreted microRNA biomarkers, and to evaluate the effectiveness of sustained multidomain interventions.

Post-acute Use of Opioids and Psychotropics in Patients after Hip Fracture: Unintended Consequences of Implementing Diagnosis-Related Grouping Payment.

OBJECTIVE: How implementing diagnostic-related grouping (DRG) payment affected the use of opioids and psychotropics by hip fracture patients following hospitalization remained unknown. DESIGN: A retrospective, pre-post design, cohort study of data excerpted from Taiwan's National Health Insurance Research database (NHIRD). SETTING AND PARTICIPANTS: Adults aged ≥ 65 years first admitted for hip fracture surgery from 2007 to 2012 were identified and divided into two 1:1 propensity-score matched groups: pre-DRG (2007-2009); DRG (2010-2012). MEASUREMENTS: The outcome measures were use of opioid and/or psychotropic drugs within 30 days, 90 days, 180 days, and 365 days after discharge. RESULTS: Data of 16,522 subjects were excerpted, and 8,261 propensity-score matched subjects each classified into the pre-DRG and DRG groups. After adjustment, the DRG group was significantly more likely than the pre-DRG group to have used antipsychotics after discharge from hip fracture surgery (≤30 days, ≤90 days, ≤180 days and ≤365 days). The DRG group also had significantly higher prescription rates of benzodiazepines and antipsychotics during the observation period. Moreover, the DRG group was less likely to use non-steroidal anti-inflammatory drugs (≤30 days, ≤90 days, ≤180 days and ≤365 days) and more likely to use acetaminophen (≤30 days, ≤180 days, and ≤365 days). CONCLUSIONS: In conclusion, DRG implementation in Taiwan substantially increased post-acute prescription of antipsychotic and psychotropic agents for hip fracture patients, and changed use of analgesics, which may result in suboptimal quality and safety for these patients. Further research is needed to evaluate the long-term outcomes of DRG implementation, and the potential benefits of appropriate post-acute care bundled with DRG payment.

Development and Validation of a Tool to Screen for Cognitive Frailty among Community-Dwelling Elders.

OBJECTIVES: Reciprocal age-related impairments in physical and cognitive functioning have been termed 'cognitive frailty', which is associated with adverse health outcomes and is a potential target for preventing or delaying the onset of disability in older people. However, cognitive frailty as currently defined is challenging to diagnose. To facilitate earlier diagnosis and intervention, we conducted this study to develop and validate a simple evidence-based instrument to identify community-dwelling elders at risk of cognitive frailty. DESIGN: Retrospective analyses of data from the I-Lan Longitudinal Aging Study (ILAS) to develop a prediction model, and from the Longitudinal Aging Study of Taipei (LAST) for external validation. SETTING: Community-dwelling adults from Taipei City, New Taipei City and Yilan (I-Lan) County, Taiwan. PARTICIPANTS: 1271 community residents ≥65 years old, without impaired global cognition or dependency for activities of daily living/instrumental activities of daily living. MEASUREMENTS: Demographic characteristics, anthropometric measurements, medical history, Mini-Mental State Examination, Montreal Cognitive Assessment, Functional Autonomy Measuring System, Functional Assessment Staging Test, Center for Epidemiologic Studies Depression Scale, handgrip strength, 6-metre walk speed. METHODS: Baseline characteristics of groups with/without cognitive frailty were analyzed and factors differing significantly in univariate analysis input to binary logistic regression to develop a cognitive frailty risk (CFR) score. RESULTS: The prevalence of cognitive frailty was 15.8% overall; ILAS 21.4%, LAST 8.4%. Predictors of CFR comprised: age ≥75 years; female sex; waist circumference ≥90 cm (male), ≥80 cm (female); calf circumference <33 cm (male), <32 cm (female); memory deficits; and diabetes mellitus. CFR ≥5/14 had sensitivity of 70%, specificity of 60%, and predictive accuracy of 72%. CONCLUSIONS: A CFR score based on simple history-taking and anthropometric measurements integrates age, sex, cardiometabolic risk, memory deficits, sarcopenia, and nutrition, with validated predictive accuracy, and could be performed easily in community settings to identify seniors with cognitive frailty for appropriate interventions.

Overexpression of paralogues of the wheat expansin gene TaEXPA8 improves low-temperature tolerance in Arabidopsis.

Low temperature is one of the important factors limiting wheat yield in cold regions. Expansins are nonenzymatic proteins that loosen cell walls and play important roles in diverse biological processes related to cell wall modification, including development and stress tolerance. Many studies have shown that expansins are involved in resistance to various abiotic stresses, such as heat and drought. However, the role of expansins in response to low-temperature stress remains unclear. Based on our previous transcriptome data of a winter wheat cultivar Dongnongdongmai 2 (DN2), we found that one of the expansin genes, TaEXPA8, was significantly induced by low temperature, indicating a role for TaEXPA8 in cold resistance. In this study, the paralogous TaEXPA8 genes TaEXPA8-A, TaEXPA8-B and TaEXPA8-D were cloned by RT-PCR. These three genes were then transformed into Arabidopsis by the floral dip method. Expression patterns of TaEXPA8 genes in different tissues and in response to several abiotic stresses and hormones were detected by quantitative real-time PCR (qRT-PCR). The results showed that TaEXPA8-A and TaEXPA8-B were expressed mainly in roots, while TaEXPA8-D was expressed predominantly in flowers. TaEXPA8 genes were induced by low-temperature and drought. The overexpression of TaEXPA8-B and TaEXPA8-D enhanced low-temperature resistance and had increased superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activity and soluble protein, MDA and proline content. In summary, our study suggested that the expansins TaEXPA8-B and TaEXPA8-D are involved in the response to low temperature and possibly play a role in cold resistance by activating the protective enzyme system.

Effect of Body Weight, Waist Circumference and Their Changes on Mortality: a 10-Year Population-based Study.

OBJECTIVES: To investigate the effect of body weight, waist circumference and their changes on all-cause and cardiovascular mortality. DESIGN: A nationwide population-based cohort study. PARTICIPANTS: 627 community-dwelling older adults. MEASUREMENTS: Participants were interviewed for demographic and anthropometric data collected. Blood were drawn for testing biochemistry data. Central obesity was defined as waist circumference is greater than 80 cm for women and 90 cm for men. Obesity, overweight, normal and underweight were defined as BMI ≥27 kg/m2 , ≥24 kg/m2 ,18.5-24 kg/m2 and < 18.5 kg/m2. Cox proportion hazard model was used to explore the impact of body weight and its change on mortality. RESULTS: The distribution of weight changes and mortality was right skewed, but U-shape of waist change for all-cause mortality was observed. Compared to normal BMI at baseline, the association between underweight (HR: 1.7, 95% CI: 0.7-4.0), overweight (HR:0.7, 95% CI:0.4-1.2) and obesity (HR:1.3,95% CI:0.8-2.3) showed insignificantly associated with all-cause mortality. The HR of those weight loss >5% (HR: 1.7, 95% CI: 1.1-2.8) and waist decrease >5% (HR: 1.7, 95% CI: 1.0-2.8) were higher than those of stable weight/waist +/- 5% over a 6-year period. Compared to those stable weight/waist, the mortality risk was similar in those of weight gain or waist increase (HR 0.7,95%CI: 0.4-1.5 and HR:0.9, 95%CI:0.4-1.6). CONCLUSION: Weight loss and waist decrease were significantly associated with long-term mortality risk, a life-course approach for body weight management is needed to pursuit the most optimal health benefits for the middle-aged and older adults.

Association of New-Onset Diabetes Mellitus in Older People and Mortality in Taiwan: A 10-Year Nationwide Population-Based Study.

OBJECTIVE: Older patients with diabetes mellitus are at a higher risk of developing diabetic macro- and micro-vascular complications and cardiovascular diseases than younger diabetes mellitus patients. However, older diabetes mellitus patients are very heterogeneous in their clinical characteristics, diabetes mellitus-related complications and age at disease onset. This study aimed to evaluate the all-cause mortality rates and adverse health outcomes among older adults with new-onset diabetes mellitus through a nationwide population-based study. DESIGN: A retrospective cohort study. SETTING: 2001-2011 data of the National Health Insurance database. POPULATION: Nationally representative sample of Taiwanese adults aged 65 years and older with propensity score-matched controls. MAIN OUTCOME MEASURES: All-cause mortality and adverse health outcomes. RESULTS: During the study period, 45.3% of patients in the diabetes mellitus cohort and 38.8% in the non-diabetes mellitus cohort died. The adjusted relative risk for mortality in the diabetes mellitus cohort compared to the non-diabetes mellitus cohort was 1.23 (95% Confidence Interval [CI]=1.16-1.30) for males and 1.27 (95%CI=1.19-1.35) for females. During the follow-up period, 8.9% of the diabetes mellitus cohort and 5.8% of the non-diabetes mellitus cohort developed cardiovascular diseases; the diabetes mellitus cohort had an adjusted relative risk of cardiovascular complications compared to the non-diabetes mellitus cohort of 1.54 (95%CI=1.36-1.75) for men and 1.70 (95%CI=1.43-2.02) for women. The adjusted relative risk of mortality in the patients with hypoglycemia compared to non-hypoglycemia patients in the diabetes mellitus cohort was 2.33 (95%CI=1.81-3.01) for men and 2.73 (95%CI=2.10-3.52) for women after adjustment for age, Charlson comorbidity index, acute coronary syndrome, respiratory disease, cancer, infectious disease and nervous system disease at baseline. CONCLUSIONS: New-onset diabetes in older adults is associated with an increased risk of mortality, and hypoglycemia is an important marker of this association. Individualized care plans stratified by age at onset, duration of disease, comorbidity and functional status, as well as hypoglycemia avoidance, would benefit the management of diabetes in older adults.

Frailty Is a Geriatric Syndrome Characterized by Multiple Impairments: A Comprehensive Approach Is Needed.

OBJECTIVE: To evaluate the prevalence of frailty and the associated multimorbidity and functional impairments among community-dwelling middle-aged and elderly people in Taiwan. DESIGN: a cross-sectional study. SETTING: communities in I-Lan County of Taiwan. PARTICIPANTS: 1839 community-dwelling people aged 50 years and older. INTERVENTION: None. MEASUREMENTS: Frailty defined by Fried's criteria, Charlson's comorbidity index (CCI), Functional Autonomy Measurement System (SMAF), Center for Epidemiologic Studies Depression Scale (CES-D), Mini-Nutrition Assessment (MNA), Mini-Mental State Examination (MMSE), and Short Form-12 quality of life questionnaire. RESULTS: Overall, 1839 subjects (mean age: 63.9±9.3 years, 47.5% males) participated in this study and men were more likely to have higher educational level, more smoking and alcohol drinking habit. The prevalence of frailty was 6.8% in this study, while pre-frailty was 40.5% and 53.7% of all participants were robust. Compared to subjects with different frailty status, age, education year, alcohol drinking, hypertension, diabetes mellitus, hyperlipidemia, CCI, walking speed, handgrip strength, score of SMAF, CES-D, MNA, MMSE, quality of life were significantly different between groups (P all< 0.05). Older age, poorer physical function, poorer cognitive function, poorer nutritional status, more depressive symptoms, higher CCI and poorer quality of life were all independently associated with frailty. CONCLUSIONS: Frailty was not simply a geriatric syndrome, but the combination of multiple geriatric syndromes. Further study is needed to evaluate the clinical benefits of intervention programs for community-dwelling middle-aged and older people to reverse frailty and its associated functional impairments.

Impact of Malnutrition on Physical, Cognitive Function and Mortality among Older Men Living in Veteran Homes by Minimum Data Set: A Prospective Cohort Study in Taiwan.

OBJECTIVES: To evaluate the prevalence of malnutrition and its impact on mortality, functional decline and cognitive impairment among elder residents in long-term care settings. DESIGNS: A prospective cohort study. SETTINGS: Two veteran homes in Taiwan. PARTICIPANTS: A total of 1,248 male residents aged equal or more than 65 years. MEASUREMENTS: Charlson's comorbidity index (CCI), Minimum data set (MDS), resident assessment protocols (RAP), Activity of daily living-Hierarchy scale, Cognitive Performance Scale, MDS Social engagement scale. RESULTS: The mean age of participants is 83.1 ± 5.1 years, and the prevalence of malnutrition was 6.1%. Inadequate dietary content (57.9%) and unintentional weight loss (31.6%) account for the majority of malnutrition identified by MDS tool. Higher 18-month mortality rate (25% vs. 14.2%), higher baseline CCI (median 1 vs. 0), and higher baseline sum of RAP triggers (median 8.5 vs. 5) were noted among residents with malnutrition. Furthermore, malnutrition was shown predictive for functional decline (OR: 3.096, 95% CI: 1.715-5.587) and potential cognitive improvement (OR: 2.469, 95% CI: 1.188-5.128) among survivors after adjustment for age, body mass index and CCI. CONCLUSION: Malnutrition among elder men residing in veteran homes was associated with multimorbidities and higher care complexity, and was predictive for mortality and functional decline.

Late-life metabolic syndrome prevents cognitive decline among older men aged 75 years and over: one-year prospective cohort study.

BACKGROUND: Although metabolic syndrome (MetS) has been reported to be associated with cognitive decline and dementia, little was known about late-life MetS and cognitive decline among older old population. The main purpose of this study was to evaluate the role of MetS and cognitive decline among men aged 75 and over in Taiwan. METHODS: This is a prospective cohort study which recruited men aged 75 years and older with intact cognitive function living in the Banciao Veterans Home, a retirement community for veterans in northern Taiwan. All participants received complete history taking, physical examinations, global cognitive tests and laboratory tests. Cognitive status was re-evaluated one year after enrollment to evaluate the role of MetS to cognitive decline in this study population. RESULTS: Overall, 338 people participated in the study and 62 of them were excluded due to low baseline MMSE score, and the remaining 276 people (mean age: 82.4±4.2 years) were enrolled for study. The prevalence of MetS and annual cognitive decline were 22.5% and 15.6%, respectively. During the follow-up period, 9 (3.3%) participants died, 229(83.0%) complete the study. Subjects with cognitive decline were older and had lower serum levels of serum total cholesterol. Multivariate logistic regression showed that older age (OR:1.13, 95% C.I.: 1.01-1.25, P=0.026) and central obesity (OR: 4.19, 95% CI: 1.26-13.91, P=0.019) were independent risk factors for cognitive decline; and MetS defined by Adult Treatment Panel III was a protective factor (OR: 0.20, 95% CI: 0.04-0.94, P=0.041). The protective effect of MetS remained the same when MetS was defined by the criteria of International Diabetes Federation. CONCLUSIONS: Age and central obesity were significant risk factors of cognitive decline, but late-life MetS, however defined, had protective effect on cognitive function. Further investigation is needed to clarify the possible mechanism of MetS and cognitive function in older adults.