The Prevalence and Correlates of Frailty in Urban and Rural Populations in Latin America, China, and India: A 10/66 Population-Based Survey.

BACKGROUND: There have been few cross-national studies of the prevalence of the frailty phenotype conducted among low or middle income countries. We aimed to study the variation in prevalence and correlates of frailty in rural and urban sites in Latin America, India, and China. METHODS: Cross-sectional population-based catchment area surveys conducted in 8 urban and 4 rural catchment areas in 8 countries; Cuba, Dominican Republic, Puerto Rico, Venezuela, Peru, Mexico, China, and India. We assessed weight loss, exhaustion, slow walking speed, and low energy consumption, but not hand grip strength. Therefore, frailty phenotype was defined on 2 or more of 4 of the usual 5 criteria. RESULTS: We surveyed 17,031 adults aged 65 years and over. Overall frailty prevalence was 15.2% (95% confidence inteval 14.6%-15.7%). Prevalence was low in rural (5.4%) and urban China (9.1%) and varied between 12.6% and 21.5% in other sites. A similar pattern of variation was apparent after direct standardization for age and sex. Cross-site variation in prevalence of frailty indicators varied across the 4 indicators. Controlling for age, sex, and education, frailty was positively associated with older age, female sex, lower socioeconomic status, physical impairments, stroke, depression, dementia, disability and dependence, and high healthcare costs. DISCUSSION: There was substantial variation in the prevalence of frailty and its indicators across sites in Latin America, India, and China. Culture and other contextual factors may impact significantly on the assessment of frailty using questionnaire and physical performance-based measures, and achieving cross-cultural measurement invariance remains a challenge. CONCLUSIONS: A consistent pattern of correlates was identified, suggesting that in all sites, the frailty screen could identify older adults with multiple physical, mental, and cognitive morbidities, disability and needs for care, compounded by socioeconomic disadvantage and catastrophic healthcare spending.

Andean microrefugia: testing the Holocene to predict the Anthropocene.

Microrefugia are important for supporting populations during periods of unfavourable climate change and in facilitating rapid migration as conditions ameliorate. With ongoing anthropogenic climate change, microrefugia could have an important conservation value; however, a simple tool has not been developed and tested to predict which settings are microrefugial. We provide a tool based on terrain ruggedness modelling of individual catchments to predict Andean microrefugia. We tested the predictions using nine Holocene Polylepis pollen records. We used the mid-Holocene dry event, a period of peak aridity for the last 100 000 yr, as an analogue climate scenario for the near future. The results suggest that sites with high terrain rugosity have the greatest chance of sustaining mesic conditions under drier-than-modern climates. Fire is a feature of all catchments; however, an increase in fire is only recorded in settings with low rugosity. Owing to rising temperatures and greater precipitation variability, Andean ecosystems are threatened by increasing moisture stress. Our results suggest that high terrain rugosity helps to create more resilient catchments by trapping moisture through orographic rainfall and providing firebreaks that shelter forest from fire. On this basis, conservation policy should target protection and management of catchments with high terrain rugosity.

The Prevalence, Correlates, Detection and Control of Diabetes among Older People in Low and Middle Income Countries. A 10/66 Dementia Research Group Population-Based Survey.

BACKGROUND: Little is known of the epidemiology of diabetes among older people in low and middle income countries. We aimed to study and compare prevalence, social patterning, correlates, detection, treatment and control of diabetes among older people in Latin America, India, China and Nigeria. METHODS: Cross-sectional surveys in 13 catchment area sites in nine countries. Diagnosed diabetes was assessed in all sites through self-reported diagnosis. Undiagnosed diabetes was assessed in seven Latin American sites through fasting blood samples (glucose > = 7 mmol/L). RESULTS: Total diabetes prevalence in catchment sites in Cuba (prevalence 24.2%, SMR 116), Puerto Rico (43.4%, 197), and urban (27.0%, 125), and rural Mexico (23.7%, 111) already exceeds that in the USA, while that in Venezuela (20.9%, 100) is similar. Diagnosed diabetes prevalence varied very widely, between low prevalences in sites in rural China (0.9%), rural India (6.6%) and Nigeria (6.0%). and 32.1% in Puerto Rico, explained mainly by access to health services. Treatment coverage varied substantially between sites. Diabetes control (40 to 61% of those diagnosed) was modest in the Latin American sites where this was studied. Diabetes was independently associated with less education, but more assets. Hypertension, central obesity and hypertriglyceridaemia, but not hypercholesterolaemia were consistently associated with total diabetes. CONCLUSIONS: Diabetes prevalence is already high in most sites. Identifying undiagnosed cases is essential to quantify population burden, particularly in least developed settings where diagnosis is uncommon. Metabolic risk factors and associated lifestyles may play an important part in aetiology, but this requires confirmation with longitudinal data. Given the high prevalence among older people, more population research is indicated to quantify the impact of diabetes, and to monitor the effect of prevention and health system strengthening on prevalence, treatment and control.

Frailty and the prediction of dependence and mortality in low- and middle-income countries: a 10/66 population-based cohort study.

BACKGROUND: In countries with high incomes, frailty indicators predict adverse outcomes in older people, despite a lack of consensus on definition or measurement. We tested the predictive validity of physical and multidimensional frailty phenotypes in settings in Latin America, India, and China. METHODS: Population-based cohort studies were conducted in catchment area sites in Cuba, Dominican Republic, Venezuela, Mexico, Peru, India, and China. Seven frailty indicators, namely gait speed, self-reported exhaustion, weight loss, low energy expenditure, undernutrition, cognitive, and sensory impairment were assessed to estimate frailty phenotypes. Mortality and onset of dependence were ascertained after a median of 3.9 years. RESULTS: Overall, 13,924 older people were assessed at baseline, with 47,438 person-years follow-up for mortality and 30,689 for dependence. Both frailty phenotypes predicted the onset of dependence and mortality, even adjusting for chronic diseases and disability, with little heterogeneity of effect among sites. However, population attributable fractions (PAF) summarising etiologic force were highest for the aggregate effect of the individual indicators, as opposed to either the number of indicators or the dichotomised frailty phenotypes. The aggregate of all seven indicators provided the best overall prediction (weighted mean PAF 41.8 % for dependence and 38.3 % for mortality). While weight loss, underactivity, slow walking speed, and cognitive impairment predicted both outcomes, whereas undernutrition predicted only mortality and sensory impairment only dependence. Exhaustion predicted neither outcome. CONCLUSIONS: Simply assessed frailty indicators identify older people at risk of dependence and mortality, beyond information provided by chronic disease diagnoses and disability. Frailty is likely to be multidimensional. A better understanding of the construct and pathways to adverse outcomes could inform multidimensional assessment and intervention to prevent or manage dependence in frail older people, with potential to add life to years, and years to life.

Differences in muscle fiber size and associated energetic costs in phylogenetically paired tropical and temperate birds.

Tropical and temperate birds provide a unique system to examine mechanistic consequences of life-history trade-offs at opposing ends of the pace-of-life spectrum; tropical birds tend to have a slow pace of life whereas temperate birds the opposite. Birds in the tropics have a lower whole-animal basal metabolic rate and peak metabolic rate, lower rates of reproduction, and longer survival than birds in temperate regions. Although skeletal muscle has a relatively low tissue-specific metabolism at rest, it makes up the largest fraction of body mass and therefore contributes more to basal metabolism than any other tissue. A principal property of muscle cells that influences their rate of metabolism is fiber size. The optimal fiber size hypothesis attempts to link whole-animal basal metabolic rate to the cost of maintaining muscle mass by stating that larger fibers may be metabolically cheaper to maintain since the surface area∶volume ratio (SA∶V) is reduced compared with smaller fibers and thus the amount of area to transport ions is also reduced. Because tropical birds have a reduced whole-organism metabolism, we hypothesized that they would have larger muscle fibers than temperate birds, given that larger muscle fibers have reduced energy demand from membrane Na(+)-K(+) pumps. Alternatively, smaller muscle fibers could result in a lower capacity for shivering and exercise. To test this idea, we examined muscle fiber size and Na(+)-K(+)-ATPase activity in 16 phylogenetically paired species of tropical and temperate birds. We found that 3 of the 16 paired comparisons indicated that tropical birds had significantly larger fibers, contrary to our hypothesis. Our data show that SA∶V is proportional to Na(+)-K(+)-ATPase activity in muscles of birds.

Linkages between mitochondrial lipids and life history in temperate and tropical birds.

Temperate birds tend to have a fast pace of life and short life spans with high reproductive output, whereas tropical birds tend to have a slower pace of life, invest fewer resources in reproduction, and have higher adult survival rates. How these differences in life history at the organismal level are rooted in differences at the cellular level is a major focus of current research. Here, we cultured fibroblasts from phylogenetically paired tropical and temperate species, isolated mitochondria from each, and compared their mitochondrial membrane lipids. We also correlated the amounts of these lipids with an important life history parameter, clutch size. We found that tropical birds tended to have less mitochondrial lipid per cell, especially less cardiolipin per cell, suggesting that cells from tropical birds have fewer mitochondria or less inner mitochondrial membrane per cell. We also found that the mitochondria of tropical birds and the species with the smallest clutch sizes had higher amounts of plasmalogens, a lipid that could serve as an antioxidant. Overall, our findings are consistent with the idea that there are underlying molecular and cellular physiological traits that could account for the differences in whole-animal physiology between animals with different life histories.

Dementia incidence and mortality in middle-income countries, and associations with indicators of cognitive reserve: a 10/66 Dementia Research Group population-based cohort study.

BACKGROUND: Results of the few cohort studies from countries with low incomes or middle incomes suggest a lower incidence of dementia than in high-income countries. We assessed incidence of dementia according to criteria from the 10/66 Dementia Research Group and Diagnostic and Statistical Manual of Mental Disorders (DSM) IV, the effect of dementia at baseline on mortality, and the independent effects of age, sex, socioeconomic position, and indicators of cognitive reserve. METHODS: We did a population-based cohort study of all people aged 65 years and older living in urban sites in Cuba, the Dominican Republic, and Venezuela, and rural and urban sites in Peru, Mexico, and China, with ascertainment of incident 10/66 and DSM-IV dementia 3-5 years after cohort inception. We used questionnaires to obtain information about age in years, sex, educational level, literacy, occupational attainment, and number of household assets. We obtained information about mortality from all sites. For participants who had died, we interviewed a friend or relative to ascertain the likelihood that they had dementia before death. FINDINGS: 12,887 participants were interviewed at baseline. 11,718 were free of dementia, of whom 8137 (69%) were reinterviewed, contributing 34,718 person-years of follow-up. Incidence for 10/66 dementia varied between 18·2 and 30·4 per 1000 person-years, and were 1·4-2·7 times higher than were those for DSM-IV dementia (9·9-15·7 per 1000 person-years). Mortality hazards were 1·56-5·69 times higher in individuals with dementia at baseline than in those who were dementia-free. Informant reports suggested a high incidence of dementia before death; overall incidence might be 4-19% higher if these data were included. 10/66 dementia incidence was independently associated with increased age (HR 1·67; 95% CI 1·56-1·79), female sex (0·72; 0·61-0·84), and low education (0·89; 0·81-0·97), but not with occupational attainment (1·04; 0·95-1·13). INTERPRETATION: Our results provide supportive evidence for the cognitive reserve hypothesis, showing that in middle-income countries as in high-income countries, education, literacy, verbal fluency, and motor sequencing confer substantial protection against the onset of dementia. FUNDING: Wellcome Trust Health Consequences of Population Change Programme, WHO, US Alzheimer's Association, FONACIT/ CDCH/ UCV.

Prevalence, distribution, and impact of mild cognitive impairment in Latin America, China, and India: a 10/66 population-based study.

BACKGROUND: Rapid demographic ageing is a growing public health issue in many low- and middle-income countries (LAMICs). Mild cognitive impairment (MCI) is a construct frequently used to define groups of people who may be at risk of developing dementia, crucial for targeting preventative interventions. However, little is known about the prevalence or impact of MCI in LAMIC settings. METHODS AND FINDINGS: Data were analysed from cross-sectional surveys established by the 10/66 Dementia Research Group and carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India on 15,376 individuals aged 65+ without dementia. Standardised assessments of mental and physical health, and cognitive function were carried out including informant interviews. An algorithm was developed to define Mayo Clinic amnestic MCI (aMCI). Disability (12-item World Health Organization disability assessment schedule [WHODAS]) and informant-reported neuropsychiatric symptoms (neuropsychiatric inventory [NPI-Q]) were measured. After adjustment, aMCI was associated with disability, anxiety, apathy, and irritability (but not depression); between-country heterogeneity in these associations was only significant for disability. The crude prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Country differences changed little (range 0.6%-4.6%) after standardization for age, gender, and education level. In pooled estimates, aMCI was modestly associated with male gender and fewer assets but was not associated with age or education. There was no significant between-country variation in these demographic associations. CONCLUSIONS: An algorithm-derived diagnosis of aMCI showed few sociodemographic associations but was consistently associated with higher disability and neuropsychiatric symptoms in addition to showing substantial variation in prevalence across LAMIC populations. Longitudinal data are needed to confirm findings-in particular, to investigate the predictive validity of aMCI in these settings and risk/protective factors for progression to dementia; however, the large number affected has important implications in these rapidly ageing settings.

Chronic diseases among older people and co-resident psychological morbidity: a 10/66 Dementia Research Group population-based survey.

BACKGROUND: This is the first study to investigate the associations between chronic health conditions of older people and their impact on co-resident psychological morbidity using population-based samples in low and middle income countries (LAMICs). METHODS: Single-phase cross-sectional catchment area surveys were undertaken in urban sites in Cuba, Dominican Republic and Venezuela, and in rural and urban catchment areas in Mexico, Peru, India and China. All residents aged 65 years and over were interviewed with a co-resident key informant. Exposures were structured clinical diagnoses (10/66 and DSM-IV dementia and ICD-10 depression), self-reported diagnosis (stroke) and physical impairments. Mediating variables were dependence and disability (WHODAS 2.0), and the outcome was co-resident psychological morbidity assessed using SRQ-20. RESULTS: Poisson regression analysis was used to estimate the prevalence ratios (PRs) for the associations between health conditions and psychological morbidity in each site, and meta-analysis was used to pool the estimates. 11,988 pairs comprising a participant and a co-resident informant were included in the analysis. After meta-analysis, independent effects were noted for depression (PR2.11; 95% CI 1.82-2.45), dementia (PR 1.98; 95% CI 1.72-2.28), stroke (PR 1.42; 95% CI 1.17-1.71) and physical impairments (PR 1.17; 95% CI 1.13-1.21). The effects were partly mediated through disability and dependence. The mean population attributable fraction of total chronic conditions was 30.1%. CONCLUSION: The prevalence of co-resident psychological morbidity is higher among co-residents of older people with chronic conditions. This effect was prominent for, but not confined to, depression and dementia. Attention needs to be directed to chronic conditions.

Leg length, skull circumference, and the prevalence of dementia in low and middle income countries: a 10/66 population-based cross sectional survey.

BACKGROUND: Adult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. There is a limited literature linking short legs and small skulls to an increased risk for cognitive impairment and dementia in late life. METHODS: One phase cross-sectional surveys were carried out of all residents aged over 65 years in 11 catchment areas in China, India, Cuba, Dominican Republic, Venezuela, Mexico and Peru (n = 14,960). The cross-culturally validated 10/66 dementia diagnosis, and a sociodemographic and risk factor questionnaire were administered to all participants, and anthropometric measures taken. Poisson regression was used to calculate prevalence ratios for the effect of leg length and skull circumference upon 10/66 dementia, controlling for age, gender, education and family history of dementia. RESULTS: The pooled meta-analyzed fixed effect for leg length (highest vs. lowest quarter) was 0.82 (95% CI, 0.68-0.98) and for skull circumference 0.75 (95% CI, 0.63-0.89). While point estimates varied between sites, the proportion of the variability attributable to heterogeneity between studies as opposed to sampling error (I2) was 0% for leg length and 22% for skull circumference. The effects were independent and not mediated by family history of dementia. The effect of skull circumference was not modified by educational level or gender, and the effect of leg length was not modified by gender. CONCLUSIONS: Since leg length and skull circumference are said to remain stable throughout adulthood into old age, reverse causality is an unlikely explanation for the findings. Early life nutritional programming, as well as neurodevelopment may protect against neurodegeneration.

Measuring disability across cultures--the psychometric properties of the WHODAS II in older people from seven low- and middle-income countries. The 10/66 Dementia Research Group population-based survey.

We evaluated the psychometric properties of the 12-item interviewer-administered screener version of the World Health Organization Disability Assessment Schedule-version II (WHODAS II) among older people living in seven low- and middle-income countries. Principal component analysis (PCA), confirmatory factor analysis (CFA) and Mokken analyses were carried out to test for unidimensionality, hierarchical structure, and measurement invariance across 10/66 Dementia Research Group sites. PCA generated a one-factor solution in most sites. In CFA, the two-factor solution generated in Dominican Republic fitted better for all sites other than rural China. The two factors were not easily interpretable, and may have been an artefact of differing item difficulties. Strong internal consistency and high factor loadings for the one-factor solution supported unidimensionality. Furthermore, the WHODAS II was found to be a 'strong' Mokken scale. Measurement invariance was supported by the similarity of factor loadings across sites, and by the high between-site correlations in item difficulties. The Mokken results strongly support that the WHODAS II 12-item screener is a unidimensional and hierarchical scale confirming to item response theory (IRT) principles, at least at the monotone homogeneity model level. More work is needed to assess the generalizability of our findings to different populations.

Contribution of chronic diseases to disability in elderly people in countries with low and middle incomes: a 10/66 Dementia Research Group population-based survey.

BACKGROUND: Disability in elderly people in countries with low and middle incomes is little studied; according to Global Burden of Disease estimates, visual impairment is the leading contributor to years lived with disability in this population. We aimed to assess the contribution of physical, mental, and cognitive chronic diseases to disability, and the extent to which sociodemographic and health characteristics account for geographical variation in disability. METHODS: We undertook cross-sectional surveys of residents aged older than 65 years (n=15 022) in 11 sites in seven countries with low and middle incomes (China, India, Cuba, Dominican Republic, Venezuela, Mexico, and Peru). Disability was assessed with the 12-item WHO disability assessment schedule 2.0. Dementia, depression, hypertension, and chronic obstructive pulmonary disease were ascertained by clinical assessment; diabetes, stroke, and heart disease by self-reported diagnosis; and sensory, gastrointestinal, skin, limb, and arthritic disorders by self-reported impairment. Independent contributions to disability scores were assessed by zero-inflated negative binomial regression and Poisson regression to generate population-attributable prevalence fractions (PAPF). FINDINGS: In regions other than rural India and Venezuela, dementia made the largest contribution to disability (median PAPF 25.1% [IQR 19.2-43.6]). Other substantial contributors were stroke (11.4% [1.8-21.4]), limb impairment (10.5% [5.7-33.8]), arthritis (9.9% [3.2-34.8]), depression (8.3% [0.5-23.0]), eyesight problems (6.8% [1.7-17.6]), and gastrointestinal impairments (6.5% [0.3-23.1]). Associations with chronic diseases accounted for around two-thirds of prevalent disability. When zero inflation was taken into account, between-site differences in disability scores were largely attributable to compositional differences in health and sociodemographic characteristics. INTERPRETATION: On the basis of empirical research, dementia, not blindness, is overwhelmingly the most important independent contributor to disability for elderly people in countries with low and middle incomes. Chronic diseases of the brain and mind deserve increased prioritisation. Besides disability, they lead to dependency and present stressful, complex, long-term challenges to carers. Societal costs are enormous. FUNDING: Wellcome Trust; WHO; US Alzheimer's Association; Fondo Nacional de Ciencia Y Tecnologia, Consejo de Desarrollo Cientifico Y Humanistico, Universidad Central de Venezuela.

Population normative data for the 10/66 Dementia Research Group cognitive test battery from Latin America, India and China: a cross-sectional survey.

BACKGROUND: 1) To report site-specific normative values by age, sex and educational level for four components of the 10/66 Dementia Research Group cognitive test battery; 2) to estimate the main and interactive effects of age, sex, and educational level by site; and 3) to investigate the effect of site by region and by rural or urban location. METHODS: Population-based cross-sectional one phase catchment area surveys were conducted in Cuba, Dominican Republic, Venezuela, Peru, Mexico, China and India. The protocol included the administration of the Community Screening Instrument for Dementia (CSI 'D', generating the COGSCORE measure of global function), and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) verbal fluency (VF), word list memory (WLM, immediate recall) and recall (WLR, delayed recall) tests. Only those free of dementia were included in the analysis. RESULTS: Older people, and those with less education performed worse on all four tests. The effect of sex was much smaller and less consistent. There was a considerable effect of site after accounting for compositional differences in age, education and sex. Much of this was accounted for by the effect of region with Chinese participants performing better, and Indian participants worse, than those from Latin America. The effect of region was more prominent for VF and WLM than for COGSCORE and WLR. CONCLUSION: Cognitive assessment is a basic element for dementia diagnosis. Age- and education-specific norms are required for this purpose, while the effect of gender can probably be ignored. The basis of cultural effects is poorly understood, but our findings serve to emphasise that normative data may not be safely generalised from one population to another with quite different characteristics. The minimal effects of region on COGSCORE and WLR are reassuring with respect to the cross-cultural validity of the 10/66 dementia diagnosis, which uses only these elements of the 10/66 battery.

Interspecific associations between circulating antioxidant levels and life-history variation in birds.

Antioxidants play an important role in protecting tissues against aging-associated oxidative damage and are thus prime candidates for relating physiological mechanisms to variation in life histories. We measured total antioxidant capacity, antioxidant response to stress, and levels of uric acid, vitamin E, and four carotenoids in 95 avian species, mostly passerines from Michigan or Panama. We compared antioxidant measures to seven variables related to life histories (clutch size, survival rate, incubation period, nestling period, basal metabolic rate, body mass, and whether the species lived in a tropical or temperate climate). Life-history-related traits varied over at least three statistically independent axes. Higher antioxidant levels were generally characteristic of more rapid development, lower survival rate, smaller body size, larger clutch size, and higher mass-adjusted metabolic rate, but the relationships of particular antioxidants with individual life-history traits showed considerable complexity. Antioxidant-life history associations differed between tropical and temperate species and varied with respect to taxonomic sampling. Vitamin E showed few relationships with life-history traits. Overall, our results partly support the hypothesis that antioxidant levels evolve to mirror free radical production. Clearly, however, the complex patterns of physiological diversification observed here result from the interplay of many factors, likely including not just investment in somatic maintenance but also phylogenetic constraint, diet, and other aspects of ecology.

Constitutive innate immunity is a component of the pace-of-life syndrome in tropical birds.

We studied the relationship between one component of immune function and basal metabolic rate (BMR), an indicator of the 'pace-of-life syndrome', among 12 tropical bird species and among individuals of the tropical house wren (Troglodytes aedon), to gain insights into functional connections between life history and physiology. To assess constitutive innate immunity we introduced a new technique in the field of ecological and evolutionary immunology that quantifies the bactericidal activity of whole blood. This in vitro assay utilises a single blood sample to provide a functional, integrated measure of constitutive innate immunity. We found that the bactericidal activity of whole blood varied considerably among species and among individuals within a species. This variation was not correlated with body mass or whole-organism BMR. However, among species, bacteria killing activity was negatively correlated with mass-adjusted BMR, suggesting that species with a slower pace-of-life have evolved a more robust constitutive innate immune capability. Among individuals of a single species, the house wren, bacteria killing activity was positively correlated with mass-adjusted BMR, pointing to physiological differences in individual quality on which natural selection potentially could act.