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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.

Objectives: Because of the continued transition to older populations, various strategies have been developed to estimate the social impact and burden of health care. Regarding mental health, a strategy in the elderly is the measurement of neuropsychiatric symptoms (NPS), these include a wide range of behavioral and psychological manifestations. These are more frequent in the presence of some diseases, such as neurodegenerative syndromes, among which dementias and Parkinson’s disease (PD) stand out. The present study seeks to analyze the frequency of NPS, its relationship with the presence or absence of neurodegenerative syndromes and some characteristics of the elderly and caregivers. Methods: This is an analysis of data from 12,865 elderly people evaluated within the protocols of the Dementia Research Group 10/66 in 6 Latin American countries (Cuba, Dominican Republic, Puerto Rico, Mexico, Venezuela and Peru). The presence or absence of parkinsonism, dementia and parkinsonism plus dementia (PDD) was identified through previously validated and published Methods. The NPS were assessed using the 12-symptom questionnaire version of the Neuropsychiatric Inventory. Other characteristics such as age, sex and education, in patients and caregivers; socioeconomic status, disability and comorbidities in the elderly; relationship with the elderly, needs and care-burden were assessed in careers. Results: The most frequent symptoms were depression and sleep disorders in the four groups (without non-NDS neurodegenerative syndromes, parkinsonism, dementia and PDD, ranging from 23% to 49%. About a third of the elderly with parkinsonism, half of those with dementia, and 3 out of 5 of the elderly with PDD had 3 or more NPS. The odds ratios (OR) of each NPS measure by multivariate logistic regression models shown OR from 1.4 to 1.9 in the presence of parkinsonism; between 1.7 and 9.3 in the presence of dementia; and between 1.9 and 10.2 in the presence of PDD. Conclusions: From a clinical and public mental health perspective, it is necessary to implement systematic Methods for NPS screening, as well as develop support strategies for families and caregivers, mainly of those with neurodegenerative syndromes.

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

Alzheimer's disease and related dementias (ADRD) disproportionately affect Latinos compared to non-Latino whites. Leveraging the non-monolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aimed to determine contributors to ADRD disparities within Latinos, focusing on genetic ancestry and SDoH. Community-dwelling participants aged 65 and older (n = 4000) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments, including sociodemographic and risk factors questionnaire, neurological exam, cognitive assessment, and blood draw. Dementia was diagnosed using the cross-culturally validated 10/66 algorithm. Individual admixture proportions were determined using sixty ancestry-informative markers. To evaluate the effect of global ancestry on dementia and cognitive performance, we used multivariate linear regression models adjusted for SDoH (e.g., gender, education level, socioeconomic status (SES), rural area, and vascular risk factors). We observed extensive three-way (African/European/Native American) genetic ancestry variation between countries (Figure 1). 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 SES (p < 0.001), and higher frequency of vascular risk factors (p < 0.001). As a result, in unadjusted analysis, individuals with predominant African ancestry exhibited a higher dementia frequency (p = 0.03) and both Native American and African ancestry predominant groups showed lower cognitive performance relative to those with higher European ancestry (p<0.001). However, 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]). We report a comprehensive characterization of the role of global genetic ancestry in cognitive performance and dementia in Latin America while controlling for SDoH. In our study, adjustment of SDoH attenuated associations between genetic ancestry, dementia probability, and cognitive performance. These findings highlight that social and environmental factors likely play more critical roles than genetic ancestry in determining racial/ethnic disparities in cognitive performance and subsequent dementia risk.

Objectives: Leveraging the non-monolithic 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 risk 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. The primary outcome measured was the risk of developing dementia. Multivariate linear regression models adjusted for SDoH were used in the main analysis. Results: We observed extensive three-way (African/European/Native American) genetic ancestry variation between countries. 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 SES (p < 0.001), and higher frequency of vascular risk factors (p < 0.001). In unadjusted analysis, American individuals with predominant African ancestry exhibited a higher dementia frequency (p = 0.03) and both Native and African ancestry predominant groups showed lower cognitive performance relative to those with higher European ancestry (p < 0.001). However, 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]). Conclusions: The findings suggest that social and environmental factors play a more crucial role than genetic ancestry in predicting dementia risk in Latin American populations. This underscores the need for public health strategies and policies that address these social determinants to reduce dementia risk in these communities effectively.

Background Alzheimer’s disease and related dementias (ADRD) disproportionately affect Latinos compared to non‐Latino whites. Leveraging the non‐monolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aimed to determine contributors to ADRD disparities within Latinos, focusing on genetic ancestry and SDoH. Method Community‐dwelling participants aged 65 and older (n = 4000) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments, including sociodemographic and risk factors questionnaire, neurological exam, cognitive assessment, and blood draw. Dementia was diagnosed using the cross‐culturally validated 10/66 algorithm. Individual admixture proportions were determined using sixty ancestry‐informative markers. To evaluate the effect of global ancestry on dementia and cognitive performance, we used multivariate linear regression models adjusted for SDoH (e.g., gender, education level, socioeconomic status (SES), rural area, and vascular risk factors). Result We observed extensive three‐way (African/European/Native American) genetic ancestry variation between countries (Figure 1). 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 SES (p < 0.001), and higher frequency of vascular risk factors (p < 0.001). As a result, in unadjusted analysis, individuals with predominant African ancestry exhibited a higher dementia frequency (p = 0.03) and both Native American and African ancestry predominant groups showed lower cognitive performance relative to those with higher European ancestry (p<0.001). However, 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]). Conclusion We report a comprehensive characterization of the role of global genetic ancestry in cognitive performance and dementia in Latin America while controlling for SDoH. In our study, adjustment of SDoH attenuated associations between genetic ancestry, dementia probability, and cognitive performance. These findings highlight that social and environmental factors likely play more critical roles than genetic ancestry in determining racial/ethnic disparities in cognitive performance and subsequent dementia risk.

INTRODUCTION This study involved evaluating a tailored genetic counseling and testing (GCT) protocol for families at risk of autosomal dominant Alzheimer's disease (ADAD) in Latin America (LatAm), focusing on essential cultural and regional adaptations. METHODS We conducted a non‐randomized controlled trial among ADAD families in Colombia and Argentina. Participants were categorized based on their decision to learn their genetic status (GS), with further comparisons between mutation‐positive versus mutation‐negative participants who learned their status. Psychological impacts were measured using validated scales for anxiety and depression. RESULTS Of the 122 eligible participants, 97 completed the GCT protocol, and 87 opted to learn their GS. There were no clinically significant differences in psychological distress between those who learned their status and those who did not, nor between mutation‐positive and mutation‐negative individuals. DISCUSSION The GCT protocol effectively managed psychological impacts in ADAD families and was positively received, demonstrating the importance of culturally adapted GCT protocols. Highlights We examined the adaptation and efficacy of a GCT protocol in LatAm for families at risk of ADAD. The GCT protocol mitigated psychological distress among at‐risk ADAD families. The study confirms the protocol's cultural appropriateness and psychological safety. Future studies should explore the long‐term psychological and public health impacts of GCT and use of GCT for treatment options.