Social determinants of health but not global genetic ancestry predict dementia prevalence in Latin America.

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.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

INTRODUCTION: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

Discovery and validation of dominantly inherited Alzheimer's disease mutations in populations from Latin America.

BACKGROUND: In fewer than 1% of patients, AD is caused by autosomal dominant mutations in either the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes. The full extent of familial AD and frequency of these variants remains understudied in Latin American (LatAm) countries. Due to the rare nature of these variants, determining the pathogenicity of a novel variant in these genes can be challenging. Here, we use a systematic approach to assign the likelihood of pathogenicity in variants from densely affected families in Latin American populations. METHODS: Clinical data was collected from LatAm families at risk for DIAD. Symptomatic family members were identified and assessed by local clinicians and referred for genetic counseling and testing. To determine the likelihood of pathogenicity among variants of unknown significance from LatAm populations, we report pedigree information, frequency in control populations, in silico predictions, and cell-based models of amyloid-beta ratios. RESULTS: We identified five novel variants in the presenilin1 (PSEN1) gene from Brazilian and Mexican families. The mean age at onset in newly identified families was 43.5 years (range 36-54). PSEN1 p.Val103_Ser104delinsGly, p.Lys395Ile, p.Pro264Se, p.Ala275Thr, and p.Ile414Thr variants have not been reported in PubMed, ClinVar, and have not been reported in dominantly inherited AD (DIAD) families. We found that PSEN1 p.Val103_Ser104delinsGly, p.Lys395Ile, p.Pro264Se, and p.Ala275Thr produce Aß profiles consistent with known AD pathogenic mutations. PSEN1 p.Ile414Thr did not alter Aß in a manner consistent with a known pathogenic mutation. CONCLUSIONS: Our study provides further insights into the genetics of AD in LatAm. Based on our findings, including clinical presentation, imaging, genetic, segregations studies, and cell-based analysis, we propose that PSEN1 p.Val103_Ser104delinsGly, p.Lys395Ile, p.Pro264Se, and p.Ala275Thr are likely pathogenic variants resulting in DIAD, whereas PSEN1 p.Ile414Thr is likely a risk factor. This report is a step forward to improving the inclusion/engagement of LatAm families in research. Family discovery is of great relevance for the region, as new initiatives are underway to extend clinical trials and observational studies to families living with DIAD.

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.

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.

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.

Cuba's Aging and Alzheimer Longitudinal Study.

Aging and Alzheimer is a prospective, longitudinal cohort study involving 2944 adults aged ≥65 years from selected areas in Cuba's Havana and Matanzas Provinces. This door-to-door study, which began in 2003, includes periodic assessments of the cohort based on an interview; physical exam; anthropometric measurements; and diagnosis of dementia and its subtypes, other mental disorders, and other chronic non-communicable diseases and their risk factors. Information was gathered on sociodemographic characteristics; disability, dependency and frailty; use of health services; and characteristics of care and caregiver burden. The first assessment also included blood tests: complete blood count, blood glucose, kidney and liver function, lipid profile and ApoE4 genotype (a susceptibility marker). In 2007-2011, the second assessment was done of 2010 study subjects aged ≥65 years who were still alive. The study provides data on prevalence and incidence of dementia and its risk factors, and of related conditions that affect the health of older adults. It also contributes valuable experiences from field work and interactions with older adults and their families. Building on lessons learned, a third assessment to be done in 2016-2018 will incorporate a community intervention strategy to respond to diseases and conditions that predispose to dementia, frailty and dependency in older adults. KEYWORDS Dementia, Alzheimer disease, chronic disease, aging, chronic illness, frailty, dependency, cohort studies, Cuba.

Incidence of dementia and association with APOE genotype in older Cubans / Incidência de demência e associação com o genótipo APOE em idosos Cubanos

Objective: In an admixed population of older Cubans, the incidence and association of APOE and sociodemographic risk factors with dementia incidence was estimated. Methods: A single-phase survey (baseline) of all over 65-year-olds residing in seven catchment areas in Cuba (n=2944) was conducted between 2003 and 2007. Dementia diagnosis was established according to DSM-IV and 10/66 criteria. APOE genotype was determined in 2520 participants. An incidence wave was conducted 4.5 years after cohort inception in order to estimate incidence and associations with sociodemographic risk factors of the APOE ?4 genotype. Results: The incidence rate of DSM IV dementia was 9.0 per 1000 person-years (95% CI 7.2-11.3) and of 10/66 dementia was 20.5 per 1000 person-years (95% CI, 17.6-23.5). Older age, a family history of dementia and APOE e4 genotype were independent risk factors for incident 10/66 dementia. APOE genotype was associated cross-sectionally with dementiaprevalence, but the effect on the incidence of dementia was attenuated, and only apparent among those in the youngest age group. Conclusion: The incidence of dementia in the older Cuban population is relatively high and similar to levels reported in Europe and North-America. The study showed that the relationship between APOE e4 and incident dementia is stronger in the younger-old than the older-old and that this change must be taken into account in models of dementia.

Objetivo: Em uma população miscigenada de cubanos idosos, estimamos a incidência de demência e a associação entre o genótipo da APOE e os fatores de risco sociodemográficos na incidência de demência. Métodos: Realizamos uma pesquisa de uma fase (linha de base) de todos os idosos com mais de 65 anos residentes em sete áreas de Cuba (n=2944), de 2003 a 2007. O diagnóstico de demência foi estabelecido de acordo com os critérios do DSM-IV e do 10/66. O genótipo APOE foi determinado em 2520 participantes. Avaliação da incidência foi conduzida 4,5 anos após a linha de base, a fim de estimar a incidência e associações com fatores de risco sociodemográficos e o genótipo APOE 4. Resultados: A taxa de incidência de demência foi de 9,0 por 1000 pessoas-ano (IC 95% 7,2-11,3) de acordo com o DSM-IV e de 20,5 por 1000 pessoas-ano (IC95%, 17,6-23,5) de acordo com o 10/66. Idade avançada, história familiar de demência e genótipo APOE 4 foram fatores de risco independentes para a incidência de demência de acordo com os critérios do 10/66. O genótipo APOE foi associado com a prevalência de demência em estudo transversal, mas o efeito sobre a incidência de demência foi atenuado, e apenas aparente entre aqueles na faixa etária mais jovem. Conclusão: A incidência de demência na população cubana mais velha é relativamente alta, semelhante às relatadas na Europa e América do Norte. O estudo mostra que a relação entre APOE 4 incidente e demência é mais forte entre os idosos mais jovens e que esta alteração deve de ser considerada em modelos de demência.

Frailty, dependency and mortality predictors in a cohort of Cuban older adults, 2003-2011.

INTRODUCTION: Population aging translates into more people with chronic non-communicable diseases, disability, frailty and dependency. The study of frailty--a clinical syndrome associated with an increased risk of falls, disability, hospitalization, institutionalization and death--is important to improve clinical practice and population health indicators. OBJECTIVES: In a cohort of older adults in Havana and Matanzas provinces, Cuba, estimate prevalence of frailty and its risk factors; determine incidence of dependency; estimate mortality risk and identify mortality predictors. METHODS: A prospective longitudinal study was conducted door to door, from June 2003 through July 2011, in a cohort of 2813 adults aged ≥65 years living in selected municipalities of Havana and Matanzas provinces; mean followup time was 4.1 years. Independent variables included demographics, behavioral risk factors and socioeconomic indicators, chronic non-communicable diseases (hypertension, stroke, dementia, depression, diabetes, anemia), number of comorbidities, and APOE ε4 genotype. Dependent variables were frailty, dependency and mortality. Criteria for frailty were slow walking speed, exhaustion, weight loss, low physical activity and cognitive decline. Prevalence and frailty risk were estimated by Poisson regression, while dependency and mortality risks and their predictors were determined using Cox regression. RESULTS: Frailty syndrome prevalence was 21.6% (CI 17.9%-23.8%) at baseline; it was positively associated with advanced age, anemia and presence of comorbidities (stroke, dementia, depression, three or more physically debilitating diseases). Male sex, higher educational level, married or partnered status, and more household amenities were inversely associated with frailty prevalence. In followup, dependency incidence was 33.1 per 1000 person-years (CI 29.1-37.6) and mortality was 55.1 per 1000 person-years. Advanced age, male sex, lower occupational status during productive years, dependency, frailty, dementia, depression, cerebrovascular disease and diabetes were all associated with higher risk of death. CONCLUSIONS: Given the challenge for developing countries presented by demographic and epidemiologic transition; the high prevalence in older adults of frailty syndrome, dependency and chronic non-communicable diseases; and the association of all these with higher mortality, attention should be targeted to older adults as a risk group. This should include greater social protection, age-appropriate health services, and modification and control of cardiovascular risk factors.

Incidence of dementia and association with APOE genotype in older Cubans.

OBJECTIVE: In an admixed population of older Cubans, the incidence and association of APOE and sociodemographic risk factors with dementia incidence was estimated. METHODS: A single-phase survey (baseline) of all over 65-year-olds residing in seven catchment areas in Cuba (n=2944) was conducted between 2003 and 2007. Dementia diagnosis was established according to DSM-IV and 10/66 criteria. APOE genotype was determined in 2520 participants. An incidence wave was conducted 4.5 years after cohort inception in order to estimate incidence and associations with sociodemographic risk factors of the APOE ε4 genotype. RESULTS: The incidence rate of DSM IV dementia was 9.0 per 1000 person-years (95% CI 7.2-11.3) and of 10/66 dementia was 20.5 per 1000 person-years (95% CI, 17.6-23.5). Older age, a family history of dementia and APOE ε4 genotype were independent risk factors for incident 10/66 dementia. APOE genotype was associated cross-sectionally with dementia prevalence, but the effect on the incidence of dementia was attenuated, and only apparent among those in the youngest age group. CONCLUSION: The incidence of dementia in the older Cuban population is relatively high and similar to levels reported in Europe and North-America. The study showed that the relationship between APOE ε4 and incident dementia is stronger in the younger-old than the older-old and that this change must be taken into account in models of dementia.

OBJETIVO: Em uma população miscigenada de cubanos idosos, estimamos a incidência de demência e a associação entre o genótipo da APOE e os fatores de risco sociodemográficos na incidência de demência. MÉTODOS: Realizamos uma pesquisa de uma fase (linha de base) de todos os idosos com mais de 65 anos residentes em sete áreas de Cuba (n=2944), de 2003 a 2007. O diagnóstico de demência foi estabelecido de acordo com os critérios do DSM-IV e do 10/66. O genótipo APOE foi determinado em 2520 participantes. Avaliação da incidência foi conduzida 4,5 anos após a linha de base, a fim de estimar a incidência e associações com fatores de risco sociodemográficos e o genótipo APOE ε4. RESULTADOS: A taxa de incidência de demência foi de 9,0 por 1000 pessoas-ano (IC 95% 7,2-11,3) de acordo com o DSM-IV e de 20,5 por 1000 pessoas-ano (IC 95%, 17,6-23,5) de acordo com o 10/66. Idade avançada, história familiar de demência e genótipo APOE ε4 foram fatores de risco independentes para a incidência de demência de acordo com os critérios do 10/66. O genótipo APOE foi associado com a prevalência de demência em estudo transversal, mas o efeito sobre a incidência de demência foi atenuado, e apenas aparente entre aqueles na faixa etária mais jovem. CONCLUSÃO: A incidência de demência na população cubana mais velha é relativamente alta, semelhante às relatadas na Europa e América do Norte. O estudo mostra que a relação entre APOE ε4 incidente e demência é mais forte entre os idosos mais jovens e que esta alteração deve de ser considerada em modelos de demência.