Search

Objectives: Studies in PD have traditionally focused on motor features, however, interest in non-motor manifestations has increased resulting in improved knowledge regarding the prognosis of the disease. Although several studies have explored the incidence of dementia in PD cohorts, these studies have been conducted mainly in reference centers in high-income countries (HIC). In this study we aimed to analyze the prevalence of cognitive impairment in people with parkinsonism and PD and its association with incident dementia in a population- based study, of elderly from six Latin American countries. Methods: This report consists of the analysis of data from a follow-up of 12,865 elderly people aged 65 years or older, carried out by 10/66 Dementia Research Group. Residents of urban and rural areas, from six low and middle- income countries (Cuba, Dominican Republic, Puerto Rico, Venezuela, Mexico and Peru). Exposures include parkinsonism and PD defined according to the UK Parkinson's Disease Society Brain Bank diagnostic criteria. Cognitive impairment was the main exposure and dementia was measured through the dementia diagnosis algorithm from 10/66 DRG. Results: At baseline, the overall prevalence of cognitive impairment was 14% (n = 1,581), in people with parkinsonism and PD, it was of 30.0% and 26.2%, respectively. Parkinsonism and PD were individually associated with prevalent and incident dementia after controlling for age, sex, and education. The pooled odds ratios from a fixed-effects meta-analysis were 2.2 (95% CI: 1.9 – 2.6) for parkinsonism and 1.9 (95% CI: 1.4 – 2.4) for PD. Regarding incident dementia, the pooled sub-Hazard ratio estimated using a competing risk model was 1.5 (95% CI: 1.2 –1.9) for parkinsonism and 1.5 (95% CI: 1.0 – 2.2) forPD. Conclusions: Parkinsonism and PD were associated cross-sectionally with the presence of cognitive impairment, and prospectively with incident dementia in elderly people in the community population of Latin America studied. Systematic screening for cognitive impairment and dementia with valid tools in PD patients may help with earlier detection of those at highest risk for adverse outcomes. Identifying modifiable risk factors could potentially lead to efficient interventions even in advanced stages of PD. [ABSTRACT FROM AUTHOR]

Background: Limited knowledge exists about the association between Parkinsonism or Parkinson's disease (PD) and cognitive impairment and dementia in Latin America. Objectives: The study aimed to determine the cross-sectional and prospective associations between Parkinsonism and PD with cognitive impairment and dementia in a large multi-country cohort in Latin America. Methods: The 10/66 is a prospective, observational cohort study. This population-based cohort study was based in six Latin American countries: Cuba, Dominican Republic, Puerto Rico, Venezuela, Mexico, and Peru. The study includes 12,865 participants from six countries, including residents aged 65 years and living in urban and rural catchment areas. Exposures included diagnosed Parkinsonism and PD defined according to the United Kingdom Parkinson's Disease Society Brain Bank diagnostic criteria. Cognitive impairment was the main outcome measure for cross-sectional analysis and dementia was used to measure the prospective association with the exposures. Logistic regression models were used to explore the association between Parkinsonism/PD with cognitive impairment at baseline. Competing risk models were used to assess the prospective association between Parkinsonism/PD with incident dementia accounting for competing risk of mortality. Individual country analyses were combined via fixed-effect meta-analysis. Results: At baseline, the prevalence of cognitive impairment in people with Parkinsonism and PD was 30% and 26.2%, respectively. Parkinsonism (OR 2.2 (95%CI 1.9 – 2.6)) and PD (1.9 (95%CI 1.4 – 2.4)) were individually associated with baseline and incident cognitive impairment after accounting for age, sex, and education, after pooling. In competing risk models, the pooled sub- hazard ratios for dementia in the fixed effect metanalysis were 1.5 (95%CI 1.2 – 1.9) for parkinsonism and 1.5 (95%CI 1.0 – 2.2) for PD. Conclusions: Parkinsonism and PD were cross-sectionally associated with cognitive impairment and prospectively associated with incident dementia in Latin America. Routine screening for cognitive impairment and dementia with validated tools in PD patients may aid earlier detection of those at greater risk ofadverseoutcomes. [ABSTRACT FROM AUTHOR]

Objective: Brief screening tools for dementia for use by non-specialists in primary care have yet to be validated in non-western settings where cultural factors and limited education may complicate the task. We aimed to derive a brief version of cognitive and informant scales from the Community Screening Instrument for Dementia (CSI-D) and to carry out initial assessments of their likely validity.Methods: We applied Mokken analysis to CSI-D cognitive and informant scale data from 15 022 participants in representative population-based surveys in Latin America, India and China, to identify a subset of items from each that conformed optimally to item response theory scaling principles. The validity coefficients of the resulting brief scales (area under ROC curve, optimal cutpoint, sensitivity, specificity and Youden's index) were estimated from data collected in a previous cross-cultural validation of the full CSI-D.Results: Seven cognitive items (Loevinger H coefficient 0.64) and six informant items (Loevinger H coefficient 0.69) were selected with excellent hierarchical scaling properties. For the brief cognitive scale, AUROC varied between 0.88 and 0.97, for the brief informant scale between 0.92 and 1.00, and for the combined algorithm between 0.94 and 1.00. Optimal cutpoints did not vary between regions. Youden's index for the combined algorithm varied between 0.78 and 1.00 by region.Conclusion: A brief version of the full CSI-D appears to share the favourable culture- and education-fair screening properties of the full assessment, despite considerable abbreviation. The feasibility and validity of the brief version still needs to be established in routine primary care. [ABSTRACT FROM AUTHOR]

Background: Little is known about the relationship between parkinsonism or Parkinson's disease (PD) and frailty in Latin America., Objective: The study aimed to determine the cross-sectional and prospective associations between parkinsonism and PD with frailty in a large multi-country cohort in Latin America. Frailty was assessed using three different models to explore which definitions are more appropriate to screen for frailty in a PD population., Methods: 12,865 older adults (aged ≥65 years) from the 10/66 population-based cohort study in six Latin American countries were analyzed. Logistic regression models assessed the cross-sectional association between parkinsonism/PD with baseline frailty. Individual country analyses were combined via fixed-effect meta-analysis. In non-frail participants who were followed up for 4 years, Cox proportional hazards regression models assessed the prospective association between parkinsonism/PD with incident frailty accounting for competing risk of mortality., Results: At baseline, the prevalence of parkinsonism and PD was 7% and 2%, respectively, and the prevalence of frailty varied across the three models with rates of 18% for frailty phenotype, 20% for frailty index and 30% for multidimensional frailty model. PD was associated with baseline and incident frailty after accounting for age, sex, and education: odds ratios and 95% confidence intervals (95% CI) for frailty were 2.49 (95% CIs 1.87-3.31), 2.42 (95% CIs 1.80-3.25), and 1.57 (95% CIs 1.16-2.21), and cause-specific hazard ratios were 1.66 (95% CIs 1.07-2.56), 1.78 (95% CIs 1.05-3.03), and 1.58 (95% CIs 0.91-2.74). Similar results were found for parkinsonism., Conclusion: Parkinsonism and PD were cross-sectionally and prospectively associated with frailty in Latin America. Routine screening for frailty in PD patients may aid earlier detection of those at greater risk of adverse outcomes., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Introduction: Leveraging the nonmonolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aim to evaluate the relative contributions of SDoH and genetic ancestry in predicting dementia prevalence in Latin American populations., Methods: Community-dwelling participants aged 65 and older (N = 3808) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments. Dementia was diagnosed using the cross-culturally validated 10/66 algorithm. Multivariate linear regression models adjusted for SDoH were used in the main analysis. This study used cross-sectional data from the 1066 population-based study., Results: Individuals with higher proportions of Native American (>70%) and African American (>70%) ancestry were more likely to exhibit factors contributing to worse SDoH, such as lower educational levels (p < 0.001), lower socioeconomic status (p < 0.001), and higher frequency of vascular risk factors (p < 0.001). After adjusting for measures of SDoH, there was no association between ancestry proportion and dementia probability, and ancestry proportions no longer significantly accounted for the variance in cognitive performance (African predominant p = 0.31 [-0.19, 0.59] and Native predominant p = 0.74 [-0.24, 0.33])., Discussion: The findings suggest that social and environmental factors play a more crucial role than genetic ancestry in predicting dementia prevalence in Latin American populations. This underscores the need for public health strategies and policies that address these social determinants to effectively reduce dementia risk in these communities., Highlights: Countries in Latin America express a large variability in social determinants of health and levels of admixture. After adjustment for downstream societal factors linked to SDoH, genetic ancestry shows no link to dementia. Population ancestry profiles alone do not influence cognitive performance. SDoH are key drivers of racial disparities in dementia and cognitive performance., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Parkinson's disease (PD) is a rapidly growing neurodegenerative disorder, but up-to-date epidemiological data are lacking in Latin America. We sought to estimate the prevalence and incidence of PD and parkinsonism in Latin America., Methods: We searched Medline, Embase, Scopus, Web of Science, Scientific Electronic Library Online, and Literatura Latino-Americana e do Caribe em Ciências da Saúde or the Latin American and Caribbean Health Science Literature databases for epidemiological studies reporting the prevalence or incidence of PD or parkinsonism in Latin America from their inception to 2022. Quality of studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Data were pooled via random-effects meta-analysis and analyzed by data source (cohort studies or administrative databases), sex, and age group. Significant differences between groups were determined by meta-regression., Results: Eighteen studies from 13 Latin American countries were included in the review. Meta-analyses of 17 studies (nearly 4 million participants) found a prevalence of 472 (95% CI, 271-820) per 100,000 and three studies an incidence of 31 (95% CI, 23-40) per 100,000 person-years for PD; and seven studies found a prevalence of 4300 (95% CI, 1863-9613) per 100,000 for parkinsonism. The prevalence of PD differed by data source (cohort studies, 733 [95% CI, 427-1255] vs. administrative databases. 114 [95% CI, 63-209] per 100,000, P < 0.01), age group (P < 0.01), but not sex (P = 0.73). PD prevalence in ≥60 years also differed significantly by data source (cohort studies. 1229 [95% CI, 741-2032] vs. administrative databases, 593 [95% CI, 480-733] per 100,000, P < 0.01). Similar patterns were observed for parkinsonism., Conclusions: The overall prevalence and incidence of PD in Latin America were estimated. PD prevalence differed significantly by the data source and age, but not sex. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Neuropsychiatric symptoms (NPSs) are common in neurodegenerative diseases; however, little is known about the prevalence of NPSs in Hispanic populations., Methods: Using data from community-dwelling participants age 65 years and older enrolled in the 10/66 study (N = 11,768), we aimed to estimate the prevalence of NPSs in Hispanic populations with dementia, parkinsonism, and parkinsonism-dementia (PDD) relative to healthy aging. The Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPSs., Results: NPSs were highly prevalent in Hispanic populations with neurodegenerative disease; approximately 34.3%, 56.1%, and 61.2% of the participants with parkinsonism, dementia, and PDD exhibited three or more NPSs, respectively. NPSs were the major contributor to caregiver burden., Discussion: Clinicians involved in the care of elderly populations should proactively screen for NPSs, especially in patients with parkinsonism, dementia, and PPD, and develop intervention plans to support families and caregivers. Highlights Neuropsychiatric symptoms (NPSs) are highly prevalent in Hispanic populations with neurodegenerative diseases. In healthy Hispanic populations, NPSs are predominantly mild and not clinically significant. The most common NPSs include depression, sleep disorders, irritability, and agitation. NPSs explain a substantial proportion of the variance in global caregiver burden., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Apolipoprotein E (APOE) is considered the major susceptibility gene for developing Alzheimer's disease. However, the strength of this risk factor is not well established across diverse Hispanic populations., Methods: We investigated the associations among APOE genotype, dementia prevalence, and memory performance (immediate and delayed recall scores) in Caribbean Hispanics (CH), African Americans (AA), Hispanic Americans (HA) and non-Hispanic White Americans (NHW). Multivariable logistic regressions and negative binomial regressions were used to examine these associations by subsample., Results: Our final dataset included 13,516 participants (5198 men, 8318 women) across all subsamples, with a mean age of 74.8 years. Prevalence of APOE ε4 allele was similar in CHs, HAs, and NHWs (21.8%-25.4%), but was substantially higher in AAs (33.6%; P < 0.001). APOE ε4 carriers had higher dementia prevalence across all groups., Discussion: APOE ε4 was similarly associated with increased relative risk of dementia and lower memory performance in all subsamples., (© 2022 the Alzheimer's Association.)

Background: Little is known about the burden of parkinsonism and Parkinson's disease (PD) in Latin America. Better understanding of health service use and clinical outcomes in PD is needed to improve its prognosis., Objective: The aim of the study was to estimate the burden of parkinsonism and PD in six Latin American countries., Methods: 12,865 participants aged 65 years and older from the 10/66 population-based cohort study were analysed. Baseline assessments were conducted in 2003-2007 and followed-up 4 years later. Parkinsonism and PD were defined using current clinical criteria or self-reported diagnosis. Logistic regression models assessed the association between parkinsonism/PD with baseline health service use (community-based care or hospitalisation in the last 3 months) and Cox proportional hazards regression models with incident dependency (subjective assessment by interviewer based on informant interview) and mortality. Separate analyses for each country were combined via fixed effect meta-analysis., Results: At baseline, the prevalence of parkinsonism and PD was 7.9% (n = 934) and 2.6% (n = 317), respectively. Only parkinsonism was associated with hospital admission at baseline (OR 1.89, 95% CI 1.30-2.74). Among 7,296 participants without dependency at baseline, parkinsonism (HR 2.34, 95% CI 1.81-3.03) and PD (2.10, 1.37-3.24) were associated with incident dependency. Among 10,315 participants with vital status, parkinsonism (1.73, 1.50-1.99) and PD (1.38, 1.07-1.78) were associated with mortality. The Higgins I2 tests showed low to moderate levels of heterogeneity across countries., Conclusions: Our findings show that older people with parkinsonism or PD living in Latin America have higher risks of developing dependency and mortality but may have limited access to health services.

Background: Age and gender specific prevalence rates for parkinsonism and Parkinson's disease (PD) are important to guide research, clinical practice, and public health planning; however, prevalence estimates in Latin America (LatAm) are limited. We aimed to estimate the prevalence of parkinsonism and PD and examine related risk factors in a cohort of elderly individuals from Latin America (LatAm)., Methods: Data from 11,613 adults (65+ years) who participated in a baseline assessment of the 10/66 study and lived in six LatAm countries were analyzed to estimate parkinsonism and PD prevalence. Crude and age-adjusted prevalence were determined by sex and country. Diagnosis of PD was established using the UK Parkinson's Disease Society Brain Bank's clinical criteria., Findings: In this cohort, the prevalence of parkinsonism was 8.0% (95% CI 7.6%-8.5%), and the prevalence of PD was 2.0% (95% CI 1.7%-2.3%). PD prevalence increased with age from 1.0 to 3.5 (65-69vs. 80 years or older, p  < 0.001). Age-adjusted prevalence rates were lower for women than for men. No significant differences were found across countries, except for lower prevalence in urban areas of Peru. PD was positively associated with depression (adjusted prevalence ratio [aPR] 2.06, 95% CI 1.40-3.01, I 2  = 56.0%), dementia (aPR 1.57, 95% CI 1.07- 2.32, I 2  = 0.0%) and educational level (aPR 1.14, 95% CI 1.01- 1.29, I 2  = 58.6%)., Interpretation: The reported prevalence of PD in LatAm is similar to reports from high-income countries (HIC). A significant proportion of cases with PD did not have a previous diagnosis, nor did they seek any medical or neurological attention. These findings underscore the need to improve public health programs for populations currently undergoing rapid demographic aging and epidemiological transition., Funding: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication., Competing Interests: Llibre-Guerra JJ, Prina M, Sosa AL, Acosta D, Guerra M, Jiménez-Velázquez I, Salas A, Llibre-Guerra JC, Valvuerdi A, Acosta I, Peeters G, Ziegemeier E, Tanner C, Juncos J and Llibre-Rodríguez J report no conflict of interest relevant to this manuscript., (© 2021 The Author(s).)

Background: The World Health Organization (WHO) has reframed health and healthcare for older people around achieving the goal of healthy ageing. The recent WHO Integrated Care for Older People (ICOPE) guidelines focus on maintaining intrinsic capacity, i.e., addressing declines in neuromusculoskeletal, vitality, sensory, cognitive, psychological, and continence domains, aiming to prevent or delay the onset of dependence. The target group with 1 or more declines in intrinsic capacity (DICs) is broad, and implementation may be challenging in less-resourced settings. We aimed to inform planning by assessing intrinsic capacity prevalence, by characterising the target group, and by validating the general approach-testing hypotheses that DIC was consistently associated with higher risks of incident dependence and death., Methods and Findings: We conducted population-based cohort studies (baseline, 2003-2007) in urban sites in Cuba, Dominican Republic, Puerto Rico, and Venezuela, and rural and urban sites in Peru, Mexico, India, and China. Door-knocking identified eligible participants, aged 65 years and over and normally resident in each geographically defined catchment area. Sociodemographic, behaviour and lifestyle, health, and healthcare utilisation and cost questionnaires, and physical assessments were administered to all participants, with incident dependence and mortality ascertained 3 to 5 years later (2008-2010). In 12 sites in 8 countries, 17,031 participants were surveyed at baseline. Overall mean age was 74.2 years, range of means by site 71.3-76.3 years; 62.4% were female, range 53.4%-67.3%. At baseline, only 30% retained full capacity across all domains. The proportion retaining capacity fell sharply with increasing age, and declines affecting multiple domains were more common. Poverty, morbidity (particularly dementia, depression, and stroke), and disability were concentrated among those with DIC, although only 10% were frail, and a further 9% had needs for care. Hypertension and lifestyle risk factors for chronic disease, and healthcare utilisation and costs, were more evenly distributed in the population. In total, 15,901 participants were included in the mortality cohort (2,602 deaths/53,911 person-years of follow-up), and 12,939 participants in the dependence cohort (1,896 incident cases/38,320 person-years). One or more DICs strongly and independently predicted incident dependence (pooled adjusted subhazard ratio 1.91, 95% CI 1.69-2.17) and death (pooled adjusted hazard ratio 1.66, 95% CI 1.49-1.85). Relative risks were higher for those who were frail, but were also substantially elevated for the much larger sub-groups yet to become frail. Mortality was mainly concentrated in the frail and dependent sub-groups. The main limitations were potential for DIC exposure misclassification and attrition bias., Conclusions: In this study we observed a high prevalence of DICs, particularly in older age groups. Those affected had substantially increased risks of dependence and death. Most needs for care arose in those with DIC yet to become frail. Our findings provide some support for the strategy of optimising intrinsic capacity in pursuit of healthy ageing. Implementation at scale requires community-based screening and assessment, and a stepped-care intervention approach, with redefined roles for community healthcare workers and efforts to engage, train, and support them in these tasks. ICOPE might be usefully integrated into community programmes for detecting and case managing chronic diseases including hypertension and diabetes., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Despite high dementia prevalence in Hispanic populations globally, especially Caribbean Hispanics, no study has comparatively examined the association between education and dementia among Hispanics living in the Caribbean Islands and older adults in the United States., Methods: We used data on 6107 respondents aged 65 and older in the baseline wave of the population-based and harmonized 10/66 survey from Cuba, the Dominican Republic, and Puerto Rico, collected between 2003 and 2008, and 11,032 respondents aged 65 and older from the U.S.-based Health and Retirement Study data in 2014, a total of 17,139 individuals. We estimated multivariable logistic regression models examining the association between education and dementia, adjusted for age, income, assets, and occupation. The models were estimated separately for the Caribbean population (pooled and by setting) and the U.S. population by race/ethnicity (Hispanic, Black, and White), followed by pooled models across all populations., Results: In the Caribbean population, the relative risk of dementia among low versus high educated adults was 1.45 for women (95% confidence interval [CI] 1.17, 1.74) and 1.92 (95% CI 1.35, 2.49) for men, smaller compared to those in the United States, especially among non-Hispanic Whites (women: 2.78, 95% CI 1.94, 3.61; men: 5.98, 95% CI 4.02, 7.95)., Discussion: The differential associations between education and dementia across the Caribbean and US settings may be explained by greater disparities in social conditions in the United States compared to the Caribbean, such as access to health care, healthy behaviors, and social stressors, which serve as potentially important mediators., Competing Interests: WD has provided consultation to Urban Institute, the Robert Wood Johnson Foundation, NIH, and Annual Review of Public Health. JL, IJG, AH, JW, IJV, DA, ML, and JLR have nothing to disclose., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Introduction: A growing number of dominantly inherited Alzheimer's disease (DIAD) cases have become known in Latin American (LatAm) in recent years. However, questions regarding mutation distribution and frequency by country remain open., Methods: A literature review was completed aimed to provide estimates for DIAD pathogenic variants in the LatAm population. The search strategies were established using a combination of standardized terms for DIAD and LatAm., Results: Twenty-four DIAD pathogenic variants have been reported in LatAm countries. Our combined dataset included 3583 individuals at risk; countries with highest DIAD frequencies were Colombia (n = 1905), Puerto Rico (n = 672), and Mexico (n = 463), usually attributable to founder effects. We found relatively few reports with extensive documentation on biomarker profiles and disease progression., Discussion: Future DIAD studies will be required in LatAm, albeit with a more systematic approach to include fluid biomarker and imaging studies. Regional efforts are under way to extend the DIAD observational studies and clinical trials to Latin America., (© 2020 the Alzheimer's Association.)

Objectives: This study was designed to explore prevalence and correlates of self-reported loneliness and to investigate whether loneliness predicts mortality among older adults (aged 65 or above) in Latin America, China and India. Methods: The study investigated population-based cross-sectional (2003-2007) and longitudinal surveys (follow-up 2007-2010) from the 10/66 Dementia Research Group project. Poisson regression and Cox regression analyses were conducted to analyse correlates of loneliness and its association with mortality. Results: The standardised prevalence of loneliness varied between 25.3 and 32.4% in Latin America and was 18.3% in India. China showed a low prevalence of loneliness (3.8%). In pooled meta-analyses, there was robust evidence to support an association between loneliness and mortality across Latin American countries (HR = 1.13, 95% CI 1.01-1.26, I 2 = 10.1%) and China (HR = 1.58, 95% CI 1.03-2.41), but there were no associations in India. Conclusion: Our findings suggest potential cultural variances may exist in the concept of loneliness in older age. The effect of loneliness upon mortality is consistent across different cultural settings excluding India. Loneliness should therefore be considered as a potential dimension of public health among older populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gao, Prina, Prince, Acosta, Luisa Sosa, Guerra, Huang, Jimenez-Velazquez, Llibre Rodriguez, Salas, Williams, Liu, Acosta Castillo and Mayston.)

Background: Cuba's life expectancy at 79 is third highest in Latin America. Many attribute this to social investments in health and education, but comparative research is sparse, thus we compare Cuba with neighboring Dominican Republic, Costa Rica due to its strong social protections, and the U.S. Given high cardiovascular mortality, we focus on cardiovascular risk factor levels. To assess the role of health care, we distinguish medically amenable biomarkers from behavioral risk factors. To assess the role of Cuba's focus on equity, we compare education gradients in risk factors., Methods: We analyze Cuban data from the 10/66 Dementia Research Group baseline survey of urban adults ages 65 plus. Comparison samples are drawn from the Dominican Republic 10/66 survey, the Costa Rican CRELES, and U.S. NHANES. We analyze cross-country levels and education gradients of medically amenable (hypertension, diabetes, hypercholesterolemia, access to health care) and behavioral (smoking, obesity) risk factors,-using sex-stratified weighted means comparisons and age-adjusted logistic regression., Results: Neither medically amenable nor behavioral risk factors are uniformly better in Cuba than comparison countries. Obesity is lower in Cuba, but male smoking is higher. Hypertension, diabetes, and hypercholesterolemia levels are high in all countries, though Cuba's are lower than Costa Rica. Hypertension awareness in Cuba is similar to Costa Rica. Cuba has a higher proportion of hypertensives on treatment than Costa Rica, though lower than the U.S. Comparative gradients by education are similarly mixed. For behavioral factors, Cuba shows the strongest gradients (primarily for men) among the countries compared: smoking improves, but obesity worsens with education. Hypertension awareness also improves with education in Cuba, but Cuba shows no significant differences by education in hypertension treatment., Conclusion: Smoking is comparatively high in Cuba, but obesity is low, and the resulting biomarkers show comparatively mixed patterns. Cuba's social protections have not eliminated strong educational gradients in behavioral risk factors, but the healthcare system appears to have eliminated disparities such as in hypertension treatment., Competing Interests: The authors have declared that no competing interests exist.

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks., Competing Interests: Agustin Ibanez is partially supported by grants from CONICET, FONCyT‐PICT 2017‐1818, FONCyT‐PICT 2017 1820, ANID/FONDAP/15150012, INECO Foundation, the Interamerican Development Bank (IDB), GBHI ALZ UK‐20‐639295, and the MULTI‐PARTNER CONSORTIUM TO EXPAND DEMENTIA RESEARCH IN LATIN AMERICA (ReDLat, supported by National Institutes of Health, National Institutes of Aging [R01 AG057234], Alzheimer's Association [SG‐20‐725707], Tau Consortium, and Global Brain Health Institute). Fabricio Ferreira de Oliveira has contributed by way of a grant from FAPESP ‐ The State of São Paulo Research Foundation (grant #2015/10109‐5). Alzheimer's Society Canada and the Weston Brain Institute (to FGF), National Institute for Translational Neuroscience (INNT/Brazil) (to FGF), the Brazilian funding agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) (to FGF). Elisa De Paula França Resende received funding from the Alzheimer's Association. Alzheimer's Association Research Grant 2018‐AARG‐591107 and REDI170583 (CDA). María Isabel Behrens is supported by grants from FONDECYT (Fondo de Desarrollo Científico y Tecnológico) Grant 1190958, FONDEF (Fondo de Fomento al Desarrollo Científico y Tecnológico Grant ID19I10302, and URedes URC‐036/17. Andrea Slachevsky is partially supported by grants from ANID/FONDAP/15150012, ANID / Fondecyt/ 1141279. Kenneth S. Kosik has support from the Alzheimer's Association and Tau Consortium. The contents of this publication are solely the responsibility of the authors and do not represent the official views of these Institutions. The other authors declare no conflicts of interest., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4)., Methods: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School., Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers., Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study., Competing Interests: Declaration of Competing Interest Richard B. Lipton Is the Edwin S. Lowe Professor of Neurology at the Albert Einstein College of Medicine in New York. He receives research support from the NIH: 2PO1 AG003949 (mPI), 5U10 NS077308 (PI), RO1 NS082432 (Investigator), 1RF1 AG057531 (Site PI), RF1 AG054548 (Investigator), 1RO1 AG048642 (Investigator), R56 AG057548 (Investigator), K23 NS09610 (Mentor), K23AG049466 (Mentor), 1K01AG054700 (Mentor). He also receives support from the Migraine Research Foundation and the National Headache Foundation. He serves on the editorial board of Neurology, senior advisor to Headache, and associate editor to Cephalalgia. He has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics and Biohaven Holdings; serves as consultant, advisory board member, or has received honoraria from: American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta. He receives royalties from Wolff’s Headache 7th and 8th Edition, Oxford Press University, 2009, Wiley and Informa. Henry Brodaty is on the Advisory Committee for Nutricia Australia; Clinincal Advisory Committee, Montefiore Home; Medical Advisory Committee, Cranbrook Care. Nikolaos Scarmeas reports personal fees from Merck Consumer Health and the NIH outside the submitted work. Mary Ganguli was on Biogen Inc.’s “Patient Journey Advisory Group” in 2016 and 2017. Allison E. Aiello is a consultant for Kinsa Inc. and has received an unrestricted gift from Gojo Inc. Henry Brodaty is on the Advisory Board of Nutricia Australia., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied., Methods: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype., Results: Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia., Conclusion: Parity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes.

Objective: The objective of this study was to estimate healthy life expectancies in eight low- and middle-income countries (LMICs), using two indicators: disability-free life expectancy (DFLE) and dependence-free life expectancy (DepFLE). Method: Using the Sullivan method, healthy life expectancy was calculated based on the prevalence of dependence and disability from the 10/66 cohort study, which included 16,990 people aged 65 or above in China, Cuba, Dominican Republic, India, Mexico, Peru, Puerto Rico, and Venezuela, and country-specific life tables from the World Population Prospects 2017. Results: DFLE and DepFLE declined with older age across all sites and were higher in women than men. Mexico reported the highest DFLE at age 65 for men (15.4, SE = 0.5) and women (16.5, SE = 0.4), whereas India had the lowest with (11.5, SE = 0.3) in men and women (11.7, SE = 0.4). Discussion: Healthy life expectancy based on disability and dependency can be a critical indicator for aging research and policy planning in LMICs.

Background: To date, dementia prediction models have been exclusively developed and tested in high-income countries (HICs). However, most people with dementia live in low-income and middle-income countries (LMICs), where dementia risk prediction research is almost non-existent and the ability of current models to predict dementia is unknown. This study investigated whether dementia prediction models developed in HICs are applicable to LMICs., Methods: Data were from the 10/66 Study. Individuals aged 65 years or older and without dementia at baseline were selected from China, Cuba, the Dominican Republic, Mexico, Peru, Puerto Rico, and Venezuela. Dementia incidence was assessed over 3-5 years, with diagnosis according to the 10/66 Study diagnostic algorithm. Discrimination and calibration were tested for five models: the Cardiovascular Risk Factors, Aging and Dementia risk score (CAIDE); the Study on Aging, Cognition and Dementia (AgeCoDe) model; the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI); the Brief Dementia Screening Indicator (BDSI); and the Rotterdam Study Basic Dementia Risk Model (BDRM). Models were tested with use of Cox regression. The discriminative accuracy of each model was assessed using Harrell's concordance (c)-statistic, with a value of 0·70 or higher considered to indicate acceptable discriminative ability. Calibration (model fit) was assessed statistically using the Grønnesby and Borgan test., Findings: 11 143 individuals without baseline dementia and with available follow-up data were included in the analysis. During follow-up (mean 3·8 years [SD 1·3]), 1069 people progressed to dementia across all sites (incidence rate 24·9 cases per 1000 person-years). Performance of the models varied. Across countries, the discriminative ability of the CAIDE (0·52≤c≤0·63) and AgeCoDe (0·57≤c≤0·74) models was poor. By contrast, the ANU-ADRI (0·66≤c≤0·78), BDSI (0·62≤c≤0·78), and BDRM (0·66≤c≤0·78) models showed similar levels of discriminative ability to those of the development cohorts. All models showed good calibration, especially at low and intermediate levels of predicted risk. The models validated best in Peru and poorest in the Dominican Republic and China., Interpretation: Not all dementia prediction models developed in HICs can be simply extrapolated to LMICs. Further work defining what number and which combination of risk variables works best for predicting risk of dementia in LMICs is needed. However, models that transport well could be used immediately for dementia prevention research and targeted risk reduction in LMICs., Funding: National Institute for Health Research, Wellcome Trust, WHO, US Alzheimer's Association, and European Research Council., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Depression and anxiety are common mental disorders in later life. Few population-based studies have investigated their potential impacts on mortality in low- and middle-income countries (LMICs). The aim of this study is to examine the associations between depression, anxiety, their comorbidity, and mortality in later life using a population-based cohort study across eight LMICs., Methods: This analysis was based on the 10/66 cohort study including 15 991 people aged 65 years or above in Cuba, Dominican Republic, Venezuela, Mexico, Peru, Puerto Rico, China, and India, with an average follow-up time of 3.9 years. Subthreshold and clinical levels of depression were determined using EURO-D and ICD-10 criteria, and anxiety was based on Geriatric Mental State (GMS)-Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT). Cox proportional hazard modelling was used to estimate how having depression, anxiety, or both was associated with mortality adjusting for sociodemographic and health factors., Results: Participants with clinical depression (hazard ratio [HR]: 1.45; 95% CI, 1.24-1.70) and subthreshold anxiety (HR: 1.26; 95% CI, 1.15-1.38) had higher risk of mortality than those without the conditions after adjusting for sociodemographic factors and health conditions. Comorbidity of depression and anxiety was associated with a 30% increased risk of mortality but the effect sizes varied across countries (Higgins I 2  = 58.8%), with the strongest association in India (HR: 1.99; 95% CI, 1.21-3.27)., Conclusions: Depression and anxiety appear to be associated with mortality in older people living in LMICs. Variation in effect sizes may indicate different barriers to health service access across countries. Future studies may investigate underlying mechanisms and identify potential interventions to reduce the impact of common mental disorders., (© 2019 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Objective: Frailty and depression are highly comorbid conditions, but the casual direction is unclear and has not been explored in low- and middle-income countries. The aim of this study was to investigate the potential impact of depression on incident frailty in older people living in Latin America., Methods: This study was based on a population-based cohort of 12,844 people aged 65 or older from six Latin American countries (Cuba, Dominican Republic, Mexico, Venezuela, Puerto Rico, and Peru), part of the 10/66 cohort study. Two types of frailty measures were used: a modified Fried frailty phenotype and a multidimensional frailty criterion, which included measures from cognition, sensory, nutrition, and physical dimensions. Depression was assessed using EURO-D and International Classification of Diseases, Tenth Revision criteria. A competing risk model was used to examine the associations between baseline depression and incidence of frailty in the 3-5 years of follow-up, accounting for sociodemographic and health factors and the competing event of frailty-free death., Results: Depression was associated with a 59% increased hazard of developing frailty using the modified Fried phenotype (subdistribution hazard ratio [SHR]: 1.59; 95% confidence interval [CI]: 1.40, 1.80) and 19% for multidimensional frailty (SHR: 1.19; 95% CI: 1.06, 1.33) after adjusting for sociodemographic factors, physical impairments, and dementia. The associations between depression and the multidimensional frailty criteria were homogenous across all the sites (Higgins I 2  = 0%)., Conclusion: Depression may play a key role in the development of frailty. Pathways addressing the association between physical and mental health in older people need to be further investigated in future research., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups., Methods and Findings: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife., Conclusions: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: AEA is a consultant for Kinsa Inc. and has received an unrestricted gift from Gojo Inc. CB is a member of the Editorial Board of PLOS Medicine. HB is on the Advisory Board of Nutricia Australia. MG was on Biogen Inc’s “Patient Journey Advisory Group” in 2016 and 2017. NS reports personal fees from Merck Consumer Health and the NIH outside the submitted work. RBL is the Edwin S. Lowe Professor of Neurology at the Albert Einstein College of Medicine in New York. He receives research support from the NIH: 2PO1 AG003949 (mPI), 5U10 NS077308 (PI), RO1 NS082432 (Investigator), 1RF1 AG057531 (Site PI), RF1 AG054548 (Investigator), 1RO1 AG048642 (Investigator), R56 AG057548 (Investigator), K23 NS09610 (Mentor), K23AG049466 (Mentor), 1K01AG054700 (Mentor). He also receives support from the Migraine Research Foundation and the National Headache Foundation. He serves on the editorial board of Neurology, senior advisor to Headache, and associate editor to Cephalalgia. He has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics and Biohaven Holdings; serves as consultant, advisory board member, or has received honoraria from: American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta. He receives royalties from Wolff’s Headache 7th and 8th Edition, Oxford Press University, 2009, Wiley and Informa. PSS received grant funding from the NIH/NIA (USA) and the NHMRC (Australia), as well as philanthropic funding through The Dementia Momentum. He is on the Australian Advisory Board of Biogen Pharmaceuticals. All other authors have declared that no competing interests exist.

Background: Adult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. Cross-sectional studies indicate inverse associations with dementia risk, but there have been few prospective studies., Methods: Population-based cohort studies in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, and anthropometric measures taken, with ascertainment of incident dementia, and mortality, three to five years later., Results: Of the original at risk cohort of 13,587 persons aged 65 years and over, 2,443 (18.0%) were lost to follow-up; 10,540 persons with skull circumference assessments were followed up for 40,466 person years, and 10,400 with leg length assessments were followed up for 39,954 person years. There were 1,009 cases of incident dementia, and 1,605 dementia free deaths. The fixed effect pooled meta-analysed adjusted subhazard ratio (ASHR) for leg length (highest vs. lowest quarter) was 0.80 (95% CI, 0.66-0.97) and for skull circumference was 1.02 (95% CI, 0.84-1.25), with no heterogeneity of effect between sites (I2 = 0%). Leg length measurements tended to be shorter at follow-up, particularly for those with baseline cognitive impairment and dementia. However, leg length change was not associated with dementia incidence (ASHR, per cm 1.006, 95% CI 0.992-1.020), and the effect of leg length was little altered after adjusting for baseline frailty (ASHR 0.82, 95% CI 0.67-0.99). A priori hypotheses regarding effect modification by gender or educational level were not supported. However, the effect of skull circumference was modified by gender (M vs F ASHR 0.86, 95% CI 0.75-0.98), but in the opposite direction to that hypothesized with a greater protective effect of larger skull dimensions in men., Conclusions: Consistent findings across settings provide quite strong support for an association between adult leg length and dementia incidence in late-life. Leg length is a relatively stable marker of early life nutritional programming, which may confer brain reserve and protect against neurodegeneration in later life through mitigation of cardiometabolic risk. Further clarification of these associations could inform predictive models for future dementia incidence in the context of secular trends in adult height, and invigorate global efforts to improve childhood nutrition, growth and development.

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., (Copyright © 2017. Published by Elsevier Inc.)

Background: Exposure to endogenous estrogen may protect against dementia, but evidence remains equivocal. Such effects may be assessed more precisely in settings where exogenous estrogen administration is rare. We aimed to determine whether reproductive period (menarche to menopause), and other indicators of endogenous estrogen exposure are inversely associated with dementia incidence., Methods: Population-based cohort studies of women aged 65 years and over in urban sites in Cuba, Dominican Republic, Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, including ages at menarche, birth of first child, and menopause, and parity, with ascertainment of incident 10/66 dementia, and mortality, three to five years later., Results: 9,428 women participated at baseline, with 72-98% responding by site. The 'at risk' cohort comprised 8,466 dementia-free women. Mean age varied from 72.0 to 75.4 years, lower in rural than urban sites and in China than in Latin America. Mean parity was 4.1 (2.4-7.2 by site), generally higher in rural than urban sites. 6,854 women with baseline reproductive period data were followed up for 26,463 person years. There were 692 cases of incident dementia, and 895 dementia free deaths. Pooled meta-analysed fixed effects, per year, for reproductive period (Adjusted Sub-Hazard Ratio [ASHR] 1.001, 95% CI 0.988-1.015) did not support any association with dementia incidence, with no evidence for effect modification by APOE genotype. No association was observed between incident dementia and; ages at menarche, birth of first child, and menopause: nulliparity; or index of cumulative endogenous estrogen exposure. Greater parity was positively associated with incident dementia (ASHR 1.030, 95% CI 1.002-1.059, I2 = 0.0%)., Conclusions: We found no evidence to support the theory that natural variation in cumulative exposure to endogenous oestrogens across the reproductive period influences dementia incidence in late life.

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.

Background: Current estimates of the prevalence of depression in later life mostly arise from studies carried out in Europe, North America and Asia. In this study we aimed to measure the prevalence of depression using a standardised method in a number of low and middle income countries (LMIC)., Methods: A one-phase cross-sectional survey involving over 17,000 participants aged 65 years and over living in urban and rural catchment areas in 13 sites from 9 countries (Cuba, Dominican Republic, Puerto Rico, Mexico, Venezuela, Peru, China, India and Nigeria). Depression was assessed and compared using ICD-10 and EURO-D criteria., Results: Depression prevalence varied across sites according to diagnostic criteria. The lowest prevalence was observed for ICD-10 depressive episode (0.3 to 13.8%). When using the EURO-D depression scale, the prevalence was higher and ranged from 1.0% to 38.6%. The crude prevalence was particularly high in the Dominican Republic and in rural India. ICD-10 depression was also associated with increased age and being female., Limitations: Generalisability of findings outside of catchment areas is difficult to assess., Conclusions: Late life depression is burdensome, and common in LMIC. However its prevalence varies from culture to culture; its diagnosis poses a significant challenge and requires proper recognition of its expression., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Cerebrovascular disease is the third-leading cause of death and the second-leading cause of disability and dementia., Objective: Determine stroke incidence and risk factors in a population of adults aged 65 and over in Cuba (Havana and Matanzas)., Material and Methods: This prospective longitudinal study, completed between April 2008 and Abril 2011, re-evaluated 2916 elderly adults with an average follow-up time of 4 years. Cases included 2316 living subjects and 600 verbal autopsies. Study variables were age, sex, educational level, self-reported health, and description of chronic diseases and substance abuse. Laboratory tests included genotyping APOE. Stroke was diagnosed based on the World Health Organization definition. We calculated the global incidence rate for stroke, broken down by sex, age group, and risk factors for incident stroke., Results: Stroke incidence was 786.2 in 100000 persons/year (95% CI: 672.3-906.4). History of alcohol consumption (HR: 3.5; 95% CI: 3.3-3.7), dementia (HR: 3.0; 95% CI, 1.6-5.5) and male sex (HR: 1.8; 95% CI, 1.2-2.8) were shown to be risk factors for incident stroke., Conclusions: Stroke incidence was similar to rates reported in developed countries and lower than that in low- to middle-income countries. Given that diabetes mellitus, heart disease, arterial hypertension, smoking, APOE4, etc. are associated with higher mortality rates, they will require separate analysis in a study of stroke risk factors., (Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Anaemia among older people is increasingly recognized as a matter of public health concern. Data from low- and middle-income countries are sparse. We surveyed 10915 people aged 65 years and over (8423 with blood tests) in catchment areas in Cuba, Dominican Republic, Puerto Rico, Venezuela and Mexico, to assess prevalence and correlates of anaemia and impact on disability. Prevalence varied widely between sites, from 6·4% in rural Mexico to 9·2% in urban Mexico, 9·8% in Venezuela, 19·2% in Cuba, 32·1% in Puerto Rico and 37·3% in Dominican Republic. Prevalence was higher in men and increased with age, but sociodemographic composition did not account for prevalence differences between sites. Standardized morbidity ratios indicated a much higher prevalence in Cuba (173), Puerto Rico (280) and Dominican Republic (332) compared with USA National Health and National Examination Surveys. Anaemia was associated with undernutrition, physical impairments, and serum creatinine. There was an association with greater African admixture in Dominican Republic but not in Cuba. African admixture is therefore unlikely to fully explain the high prevalence in the Caribbean islands, which may also arise from environmental, possibly dietary factors. Given an important independent contribution of anaemia to disability, more research is needed to identify preventable and treatable causes., (© 2012 Blackwell Publishing Ltd.)

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: In a multi-site population-based study in several middle-income countries, we aimed to investigate relative contributions of care arrangements and characteristics of carers and care recipients to strain among carers of people with dementia. Based on previous research, hypotheses focused on carer sex, care inputs, behavioural and psychological symptoms (BPSD) and socioeconomic status, together with potential buffering effects of informal support and employing paid carers., Methods: In population-based catchment area surveys in 11 sites in Latin America, India and China, we analysed data collected from people with dementia and care needs, and their carers. Carer strain was assessed with the Zarit Burden Interview., Results: With 673 care recipient/carer dyads interviewed (99% of those eligible), mean Zarit Burden Interview scores ranged between 17.1 and 27.9 by site. Women carers reported more strain than men. The most substantial correlates of carer strain were primary stressors BPSD, dementia severity, needs for care and time spent caring. Socioeconomic status was not associated with carer strain. Those cutting back on work experienced higher strain. There was tentative evidence for a protective effect of having additional informal or paid support., Conclusions: Our findings underline the global impact of caring for a person with dementia and support the need for scaling up carer support, education and training. That giving up work to care was prevalent and associated with substantial increased strain emphasizes the economic impact of caring on the household. Carer benefits, disability benefits for people with dementia and respite care should all be considered., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: Even in low and middle income countries most deaths occur in older adults. In Europe, the effects of better education and home ownership upon mortality seem to persist into old age, but these effects may not generalise to LMICs. Reliable data on causes and determinants of mortality are lacking., Methods and Findings: The vital status of 12,373 people aged 65 y and over was determined 3-5 y after baseline survey in sites in Latin America, India, and China. We report crude and standardised mortality rates, standardized mortality ratios comparing mortality experience with that in the United States, and estimated associations with socioeconomic factors using Cox's proportional hazards regression. Cause-specific mortality fractions were estimated using the InterVA algorithm. Crude mortality rates varied from 27.3 to 70.0 per 1,000 person-years, a 3-fold variation persisting after standardisation for demographic and economic factors. Compared with the US, mortality was much higher in urban India and rural China, much lower in Peru, Venezuela, and urban Mexico, and similar in other sites. Mortality rates were higher among men, and increased with age. Adjusting for these effects, it was found that education, occupational attainment, assets, and pension receipt were all inversely associated with mortality, and food insecurity positively associated. Mutually adjusted, only education remained protective (pooled hazard ratio 0.93, 95% CI 0.89-0.98). Most deaths occurred at home, but, except in India, most individuals received medical attention during their final illness. Chronic diseases were the main causes of death, together with tuberculosis and liver disease, with stroke the leading cause in nearly all sites., Conclusions: Education seems to have an important latent effect on mortality into late life. However, compositional differences in socioeconomic position do not explain differences in mortality between sites. Social protection for older people, and the effectiveness of health systems in preventing and treating chronic disease, may be as important as economic and human development.

Objectives: Despite the growing importance of stroke in developing countries, little is known of stroke burden in survivors. The authors investigated the prevalence of self-reported stroke, stroke-related disability, dependence and care-giver strain in Latin America (LA), China and India., Methods: Cross-sectional surveys were conducted on individuals aged 65+ (n=15 022) living in specified catchment areas. Self-reported stroke diagnosis, disability, care needs and care giver burden were assessed using a standardised protocol. For those reporting stroke, the correlates of disability, dependence and care-giver burden were estimated at each site using Poisson or linear regression, and combined meta-analytically., Results: The prevalence of self-reported stroke ranged between 6% and 9% across most LA sites and urban China, but was much lower in urban India (1.9%), and in rural sites in India (1.1%), China (1.6%) and Peru (2.7%). The proportion of stroke survivors needing care varied between 20% and 39% in LA sites but was higher in rural China (44%), urban China (54%) and rural India (73%). Comorbid dementia and depression were the main correlates of disability and dependence., Conclusion: The prevalence of stroke in urban LA and Chinese sites is nearly as high as in industrialised countries. High levels of disability and dependence in the other mainly rural and less-developed sites suggest underascertainment of less severe cases as one likely explanation for the lower prevalence in those settings. As the health transition proceeds, a further increase in numbers of older stroke survivors is to be anticipated. In addition to prevention, stroke rehabilitation and long-term care needs should be addressed.

Background: To describe patterns of recent health service utilisation, and consequent out-of-pocket expenses among older people in countries with low and middle incomes, and to assess the equity with which services are accessed and delivered., Methods: 17,944 people aged 65 years and over were assessed in one-phase population-based cross-sectional surveys in geographically-defined catchment areas in nine countries - urban and rural sites in China, India, Mexico and Peru, urban sites in Cuba, Dominican Republic, Puerto Rico and Venezuela, and a rural site in Nigeria. The main outcome was use of community health care services in the past 3 months. Independent associations were estimated with indicators of need (dementia, depression, physical impairments), predisposing factors (age, sex, and education), and enabling factors (household assets, pension receipt and health insurance) using Poisson regression to generate prevalence ratios and fixed effects meta-analysis to combine them., Results: The proportion using healthcare services varied from 6% to 82% among sites. Number of physical impairments (pooled prevalence ratio 1.37, 95% CI 1.26-1.49) and ICD-10 depressive episode (pooled PR 1.21, 95% CI 1.07-1.38) were associated with service use, but dementia was inversely associated (pooled PR 0.93, 95% CI 0.90-0.97). Other correlates were female sex, higher education, more household assets, receiving a pension, and health insurance. Standardisation for age, sex, physical impairments, depression and dementia did not explain variation in service use. There was a strong borderline significant ecological correlation between the proportion of consultations requiring out-of-pocket costs and the prevalence of health service use (r = -0.50, p = 0.09)., Conclusions: While there was little evidence of ageism, inequity was apparent in the independent enabling effects of education and health insurance cover, the latter particularly in sites where out-of-pocket expenses were common, and private health insurance an important component of healthcare financing. Variation in service use among sites was most plausibly accounted for by stark differences in the extent of out-of-pocket expenses, and the ability of older people and their families to afford them. Health systems that finance medical services through out-of-pocket payments risk excluding the poorest older people, those without a secure regular income, and the uninsured.

Background: Dementia is becoming a major public health problem in Latin America (LA), yet epidemiological information on dementia remains scarce in this region. This study analyzes data from epidemiological studies on the prevalence of dementia in LA and compares the prevalence of dementia and its causes across countries in LA and attempts to clarify differences from those of developed regions of the world., Methods: A database search for population studies on rates of dementia in LA was performed. Abstracts were also included in the search. Authors of the publications were invited to participate in this collaborative study by sharing missing or more recent data analysis with the group., Results: Eight studies from six countries were included. The global prevalence of dementia in the elderly (> or =65 years) was 7.1% (95% CI: 6.8-7.4), mirroring the rates of developed countries. However, prevalence in relatively young subjects (65-69 years) was higher in LA studies The rate of illiteracy among the elderly was 9.3% and the prevalence of dementia in illiterates was two times higher than in literates. Alzheimer's disease was the most common cause of dementia., Conclusions: Compared with studies from developed countries, the global prevalence of dementia in LA proved similar, although a higher prevalence of dementia in relatively young subjects was evidenced, which may be related to the association between low educational level and lower cognitive reserve, causing earlier emergence of clinical signs of dementia in the LA elderly population.

Background: Studies have suggested that the prevalence of dementia is lower in developing than in developed regions. We investigated the prevalence and severity of dementia in sites in low-income and middle-income countries according to two definitions of dementia diagnosis., Methods: We undertook one-phase cross-sectional surveys of all residents aged 65 years and older (n=14 960) in 11 sites in seven low-income and middle-income countries (China, India, Cuba, Dominican Republic, Venezuela, Mexico, and Peru). Dementia diagnosis was made according to the culturally and educationally sensitive 10/66 dementia diagnostic algorithm, which had been prevalidated in 25 Latin American, Asian, and African centres; and by computerised application of the dementia criterion from the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). We also compared prevalence of DSM-IV dementia in each of the study sites with that from estimates in European studies., Findings: The prevalence of DSM-IV dementia varied widely, from 0.3% (95% CI 0.1-0.5) in rural India to 6.3% (5.0-7.7) in Cuba. After standardisation for age and sex, DSM-IV prevalence in urban Latin American sites was four-fifths of that in Europe (standardised morbidity ratio 80 [95% CI 70-91]), but in China the prevalence was only half (56 [32-91] in rural China), and in India and rural Latin America a quarter or less of the European prevalence (18 [5-34] in rural India). 10/66 dementia prevalence was higher than that of DSM-IV dementia, and more consistent across sites, varying between 5.6% (95% CI 4.2-7.0) in rural China and 11.7% (10.3-13.1) in the Dominican Republic. The validity of the 847 of 1345 cases of 10/66 dementia not confirmed by DSM-IV was supported by high levels of associated disability (mean WHO Disability Assessment Schedule II score 33.7 [SD 28.6])., Interpretation: As compared with the 10/66 dementia algorithm, the DSM-IV dementia criterion might underestimate dementia prevalence, especially in regions with low awareness of this emerging public-health problem.

We studied a Cuban family with presenile dementia (autosomal dominant) consisting of 281 members within six generations, the proband descended from a Spanish founder. Mean age at onset was 59 years of age. Memory impairment was the main symptom in all patients, additionally, ischemic episodes were described in 4 (n = 18) patients. Neuropathological examination of brain material (1 patient) revealed neuronal loss, amyloid plaques, and neurofibrillary tangles. Thirty DNA samples were genotyped (regions on chromosome 1, 3, 10, 12, 14, 17, 19, 20, and 21). A maximum Lod score of 3.79 at theta = 0 was obtained for marker D14S43, located in a 9-cM interval in which all patients shared the same haplotype. Sequencing of the PSEN1 gene revealed a heterozygous base substitution, C520A (exon 6), which is predicted to cause an amino acid change from leucine to methionine in the TMIII of the presenilin 1 protein. The mutation was found to co-segregate with the disease phenotype and the associated disease haplotype. The C --> A change was not observed in 80 control chromosomes from the Cuban population. Leucine at position 174 is highly conserved among species and is identical in presenilin 1 and presenilin 2 proteins. We propose the L174 M mutation might lead to an abnormal N-terminal and probably C-terminal fragments and malfunction of the protein complex. In conclusion, we found a novel PSEN1 mutation in a large family with clinical and pathological diagnosis of early onset familial Alzheimer disease, which may be relevant for other Hispanic populations.