Prevalence and Incidence of Parkinson's Disease in Latin America: A Meta-Analysis.

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.

Burden of Parkinsonism and Parkinson's Disease on Health Service Use and Outcomes in Latin America.

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.

Prevalence and impact of neuropsychiatric symptoms in normal aging and neurodegenerative syndromes: A population-based study from Latin America.

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.

Prevalence of parkinsonism and Parkinson disease in urban and rural populations from Latin America: A community based study.

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.

Race, Genetic Admixture, and Cognitive Performance in the Cuban Population.

BACKGROUND: Population aging will lead to a dramatic increase in dementia prevalence, which will disproportionally affect racial minorities. The presence of racial differences in dementia prevalence has been widely reported in United States, but there are no relevant studies on this topic in low- and middle-income countries. METHODS: In a cross-sectional survey, 2944 older Cubans were recruited at a community-based level aimed to identify the effects of self-identified race and genetic admixture on cognitive performance. Dementia diagnosis was established using 10/66 Dementia and DSM-IV criteria. APOE-ε4 genotype was determined in 2511 (85%) and genetic admixture was completed for all dementia cases and in a randomly selected sample of cognitive healthy participants (218 dementia cases and 367 participants without dementia). RESULTS: The overall prevalence of dementia was 8.7%, without large or statistically significant differences on dementia prevalence (p = .12) by self-identified race. Mean cognitive scores were similar across racial groups (p = .46). After controlling for age, sex, and education, greater proportion of African ancestry was not associated with cognitive performance (p = .17). CONCLUSIONS: We found no evidence of an independent effect of self-identified race and/or population ancestry on dementia prevalence or cognitive performance. This suggests that observed differences in dementia prevalence among diverse populations may be driven primarily by social determinants of health.

Working Group Recommendations for the Practice of Teleneuropsychology in Latin America.

OBJECTIVE: Teleneuropsychology (teleNP) could potentially expand access to services for patients who are confined, have limited personal access to healthcare, or live in remote areas. The emergence of the COVID-19 pandemic has significantly increased the use of teleNP for cognitive assessments. The main objective of these recommendations is to identify which procedures can be potentially best adapted to the practice of teleNP in Latin America, and thereby facilitate professional decision-making in the region. METHOD: Steps taken to develop these recommendations included (1) formation of an international working group with representatives from 12 Latin American countries; (2) assessment of rationale, scope, and objectives; (3) formulation of clinical questions; (4) evidence search and selection; (5) evaluation of existing evidence and summary; and (6) formulation of recommendations. Levels of evidence were graded following the Oxford Centre for Evidence-Based Medicine system. Databases examined included PubMed, WHO-IRIS, WHO and PAHO-IRIS, Índice Bibliográfico Español en Ciencias de la Salud (IBCS), and LILACS. RESULTS: Working group members reviewed 18,400 titles and 422 abstracts and identified 19 articles meeting the criteria for level of evidence, categorization, and elaboration of recommendations. The vast majority of the literature included teleNP tests in the English language. The working group proposed a series of recommendations that can be potentially best adapted to the practice of teleNP in Latin America. CONCLUSIONS: There is currently sufficient evidence to support the use of videoconferencing technology for remote neuropsychological assessments. These recommendations will likely contribute to the advancement of teleNP research and practice in the region.

Loneliness Among Older Adults in Latin America, China, and India: Prevalence, Correlates and Association With Mortality.

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, I2 = 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.

Intrinsic capacity and its associations with incident dependence and mortality in 10/66 Dementia Research Group studies in Latin America, India, and China: A population-based cohort study.

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.

Fragilidad como factor de riesgo de demencia en adultos mayores / Frailty as a risk factor for dementia in older adults

El síndrome de fragilidad se caracteriza por una mayor vulnerabilidad y riesgo de deterioro funcional y cognitivo ante un mínimo estrés, siendo la demencia una de las principales causas de discapacidad y dependencia entre los adultos mayores a nivel global, con un impacto físico, psicológico, social y económico no solo en las personas que la padecen, sino también en sus cuidadores. El objetivo de este estudio fue determinar la prevalencia de demencia según fenotipos de fragilidad y estimar la asociación de fragilidad y demencia en adultos mayores. Se tomó como referencia la base de datos del estudio Envejecimiento y Alzheimer (10-66), realizándose una investigación descriptiva de corte transversal, en 2024 adultos mayores de 65 años pertenecientes a siete áreas de salud de La Habana, Cuba. Se efectuó un análisis univariado para los efectos independientes de cada una de las variables y la variable de respuesta o dependiente (demencia) considerando esta asociación significativa cuando (p≤0.001) o por criterio de expertos y un análisis multivariado a través de la Regresión de Poisson. Existió una alta prevalencia de demencia en los sujetos con fragilidad 30,6 %(IC 95 % 22,4 - 39,6), donde la relación entre las mismas mostró una asociación significativa. Las personas frágiles presentaron un riesgo mayor de padecer demencia, con un PR 2.74 (IC 95% 2,29-3,29). La fragilidad se comportó como un factor de riesgo para el desarrollo de demencia.

Frailty syndrome is characterized by a greater vulnerability and risk of functional and cognitive deterioration in the face of minimal stress, with dementia being one of the main causes of disability and dependency among older adults globally, with a physical, psychological, and social impact. and economic not only in the people who suffer from it, but also in their caregivers. The objective of this study was to determine the prevalence of dementia according to frailty phenotypes and to estimate the association of frailty and dementia in older adults. The database of the Aging and Alzheimer study (10-66) was taken as a reference, carrying out a descriptive cross-sectional investigation in 2024 adults over 65 years of age belonging to seven health areas in Havana, Cuba. A univariate analysis was carried out for the independent effects of each of the variables and the response or dependent variable (dementia), considering this significant association when (p≤0.001) or by expert criteria and a multivariate analysis through the regression of Poisson. There was a high prevalence of dementia in subjects with frailty 30.6% (95% CI 22.4 - 39.6), where the relationship between them showed a significant association. Frail people had a higher risk of suffering from dementia, with a PR 2.74 (CI 95% 2.29-3.29). Frailty behaved as a risk factor for the development of dementia.

Cuba's cardiovascular risk factors: International comparison of levels and education gradients.

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.

A Brief Digital Cognitive Assessment for Detection of Cognitive Impairment in Cuban Older Adults.

BACKGROUND: Rapid technological advances offer a possibility to develop cost-effective digital cognitive assessment tools. However, it is unclear whether these measures are suitable for application in populations from Low and middle-income countries (LMIC). OBJECTIVE: To examine the accuracy and validity of the Brain Health Assessment (BHA) in detecting cognitive impairment in a Cuban population. METHODS: In this cross-sectional study, 146 participants (cognitively healthy = 53, mild cognitive impairment (MCI) = 46, dementia = 47) were recruited at primary care and tertiary clinics. The main outcomes included: accuracy of the BHA and the Montreal Cognitive Assessment (MoCA) in discriminating between controls and cognitively impaired groups (MCI and dementia) and correlations between the BHA subtests of memory, executive functions, and visuospatial skills and criterion-standard paper-and-pencil tests in the same domains. RESULTS: The BHA had an AUC of 0.95 (95% CI: 0.91-0.98) in discriminating between controls and cognitively impaired groups (MCI and dementia, combined) with 0.91 sensitivity at 0.85 specificity. In discriminating between control and MCI groups only, the BHA tests had an AUC of 0.94 (95% CI: 0.90-0.99) with 0.71 sensitivity at 0.85 specificity. Performance was superior to the MoCA across all diagnostic groups. Concurrent and discriminant validity analyses showed moderate to strong correlations between the BHA tests and standard paper-and-pencil measures in the same domain and weak correlations with standard measures in unrelated domains. CONCLUSION: The BHA has excellent performance characteristics in detecting cognitive impairment including dementia and MCI in a Hispanic population in Cuba and outperformed the MoCA. These results support potential application of digital cognitive assessment for older adults in LMIC.

Dominantly inherited Alzheimer's disease in Latin America: Genetic heterogeneity and clinical phenotypes.

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.

The impact of SARS-CoV-2 in dementia across Latin America: A call for an urgent regional plan and coordinated response.

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.

Does parity matter in women's risk of dementia? A COSMIC collaboration cohort study.

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.

Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment.

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.

APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline.

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.

Prediction of dementia risk in low-income and middle-income countries (the 10/66 Study): an independent external validation of existing models.

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.

Dementia Research in the Caribbean Hispanic Islands: Present Findings and Future Trends.

During the last decade, the Caribbean Hispanic islands experienced accelerated demographic aging, representing the fastest aging region within Latin America. Age-related non-communicable diseases, including dementia, are now reported at high prevalence. The Caribbean islands share similar genetic ancestry, culture, migration patterns, and risk profiles, providing a unique setting to understand dementia in the Caribbean-Hispanics. This perspective article aimed to describe the impact of dementia in the Caribbean, at a local and regional level and reflect on research strategies to address dementia. We report on 10/66 project findings, described research projects and regional plans for the region. According to our results, the prevalence of dementia in the Caribbean is the highest in Latin America, with 11.7% in Dominican Republic, 11.6% in Puerto Rico, and 10.8% in Cuba. Preliminary data from new waves of the 10/66 study shows increasing numbers of dementia cases. Furthermore, dementia is expected to be one of the most serious medical and social issues confronted by Caribbean health systems. However, there is a scarcity of knowledge, awareness, and health services to deal with this public health crisis. In light of the new evidence, local and regional strategies are underway to better understand dementia trends for the region and develop policies aimed to decrease the impact of dementia. Implementation of our national plans is critical to deal with an aging population with high dementia rates. Current recommendations include emphasizing public health prevention campaigns to address modifiable risk factors and expand support to caregiver and family interventions.

Dependence- and Disability-Free Life Expectancy Across Eight Low- and Middle-Income Countries: A 10/66 Study.

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.