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Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure. This perspective paper was produced by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) and discusses the field's current status on the cross-cultural aspects of basic and translational research in FTD (including that focused on epidemiology, genetics, biomarkers, and treatment). It subsequently provides a summary of gaps and needs to address the disparities and advance global FTD biomedical research.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of diversity (including geographical, socioeconomic, sociodemographic, sex and neurodegeneration) on the brain-age gap is unknown. We analyzed datasets from 5,306 participants across 15 countries (7 Latin American and Caribbean countries (LAC) and 8 non-LAC countries). Based on higher-order interactions, we developed a brain-age gap deep learning architecture for functional magnetic resonance imaging (2,953) and electroencephalography (2,353). The datasets comprised healthy controls and individuals with mild cognitive impairment, Alzheimer disease and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (functional magnetic resonance imaging: mean directional error = 5.60, root mean square error (r.m.s.e.) = 11.91; electroencephalography: mean directional error = 5.34, r.m.s.e. = 9.82) associated with frontoposterior networks compared with non-LAC models. Structural socioeconomic inequality, pollution and health disparities were influential predictors of increased brain-age gaps, especially in LAC (R² = 0.37, F² = 0.59, r.m.s.e. = 6.9). An ascending brain-age gap from healthy controls to mild cognitive impairment to Alzheimer disease was found. In LAC, we observed larger brain-age gaps in females in control and Alzheimer disease groups compared with the respective males. The results were not explained by variations in signal quality, demographics or acquisition methods. These findings provide a quantitative framework capturing the diversity of accelerated brain aging.

Resumen: Introducción: El Addenbrooke's Cognitive Examination III (ACE-III) es una adaptación del test de cribado ACE, la cual ha demostrado tener una alta sensibilidad y especificidad para detectar disfunción cognitiva en pacientes con demencia y otras patologías neurológicas y psiquiátricas. Si bien el ACE-III ya ha sido validado en castellano (España), este no ha sido validado en Latinoamérica. El objetivo del presente estudio fue validar el ACE-III en una población argentina y chilena. Métodos: Se evaluó un grupo de pacientes con enfermedad de Alzheimer (n = 70), un grupo de pacientes con la variante conductual de la demencia frontotemporal (n = 31) y un grupo control (n = 139) con la versión en español del ACE-III; reclutados en centros médicos de ambos países. Resultados: La versión argentina-chilena del ACE-III presentó una buena consistencia interna (alfa de Cronbach = 0,87). Se hallaron diferencias significativas en los valores totales del ACE-III entre el grupo control y el grupo de demencias (p< 0,05) y entre ambos grupos de demencia (p< 0,05). Con un punto de corte de 86, el 98,6% de los pacientes con DTA, el 83,9% de pacientes con variante conductual de la demencia frontotemporal y el 84,2% de los controles fue correctamente clasificado. Conclusiones: El presente estudio ha demostrado que el ACE-III continúa siendo una herramienta útil para la detección de la disfunción cognitiva en la demencia. Abstract: Background: The Addenbrooke's Cognitive Examination III (ACE-III), an adaptation of the ACE cognitive screening test, has been demonstrated to have high sensitivity and specificity in detecting cognitive impairment in patients with dementia and other neurological and psychiatric disorders. Although the Spanish-language version of the ACE-III has already been validated in Spain, it is yet to be validated in Latin America. The aim of this study was to validate the ACE-III test in an Argentinean and Chilean population. Methods: ACE-III was administered to 70 patients with Alzheimer disease, 31 patients with behavioural variant frontotemporal dementia, and a control group of 139 healthy volunteers. Participants were recruited at centres in both countries. Results: The Spanish-language version of ACE-III was found to have good internal consistency (Cronbach's alpha = 0.87). We found significant differences in total ACE-III scores between patients with Alzheimer disease and controls (p

Background: The Addenbrooke's Cognitive Examination III (ACE-III), an adaptation of the ACE cognitive screening test, has been demonstrated to have high sensitivity and specificity in detecting cognitive impairment in patients with dementia and other neurological and psychiatric disorders. Although the Spanish-language version of the ACE-III has already been validated in Spain, it is yet to be validated in Latin America. The aim of this study was to validate the ACE-III test in an Argentinean and Chilean population. Methods: ACE-III was administered to 70 patients with Alzheimer disease, 31 patients with behavioural variant frontotemporal dementia, and a control group of 139 healthy volunteers. Participants were recruited at centres in both countries. Results: The Spanish-language version of ACE-III was found to have good internal consistency (Cronbach's alpha = 0.87). We found significant differences in total ACE-III scores between patients with Alzheimer disease and controls (P

BACKGROUND: Education influences brain health and dementia. However, its impact across regions, specifically Latin America (LA) and the United States (US), is unknown. METHODS: A total of 1412 participants comprising controls, patients with Alzheimers disease (AD), and frontotemporal lobar degeneration (FTLD) from LA and the US were included. We studied the association of education with brain volume and functional connectivity while controlling for imaging quality and variability, age, sex, total intracranial volume (TIV), and recording type. RESULTS: Education influenced brain measures, explaining 24%-98% of the geographical differences. The educational disparities between LA and the US were associated with gray matter volume and connectivity variations, especially in LA and AD patients. Education emerged as a critical factor in classifying aging and dementia across regions. DISCUSSION: The results underscore the impact of education on brain structure and function in LA, highlighting the importance of incorporating educational factors into diagnosing, care, and prevention, and emphasizing the need for global diversity in research. HIGHLIGHTS: Lower education was linked to reduced brain volume and connectivity in healthy controls (HCs), Alzheimers disease (AD), and frontotemporal lobar degeneration (FTLD). Latin American cohorts have lower educational levels compared to the those in the United States. Educational disparities majorly drive brain health differences between regions. Educational differences were significant in both conditions, but more in AD than FTLD. Education stands as a critical factor in classifying aging and dementia across regions.

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.

Resumen: Antecedentes: En los próximos 20 años se duplicará la cantidad de personas con deterioro cognitivo (DC) apremiando su pronta detección. Objetivos: Validar una prueba de cribado de DC aplicable en

Background: The prevalence of cognitive impairment (CI) will double in the next 20 years, making early detection a key priority. Objectives: Validation of a 5-minute CI screening test. Methods: Adults aged 60 years and older were recruited from memory clinics and the community at large in the Santiago, Chile metropolitan area. Based on clinical examination they were categorised as No CI (NCI), Mild CI (MCI) and dementia sufferers (DS). We measured the validity of a new test, MEFO, evaluating memory (5 points), phonetic verbal fluency (2 points) and orientation (6 points) by comparing its results with those from the MMSE. Results: We evaluated 214 subjects, comprising 49 with dementia, 47 with MCI, and 118 with no CI. The MEFO differentiated between all 3 groups whereas the MMSE did not discriminate between the MCI and NCI groups. The area under the ROC curve (AUC) for the MEFO distinguishing NCI subjects from dementia sufferers was 0.97; for NCI vs CI (dementia + MCI), 0.89; and for NCI vs MCI, 0.80. On the MMSE these values were 0.95, 0.84, and 0.73, respectively. A cut-off score of 6/7 on the MEFO identified dementia sufferers with a sensitivity of 86% and a specificity of 96%. A cut-off score of 8/9 distinguished CI from NCI subjects with a sensitivity of 83% and a specificity of 75%. Conclusions: The MEFO is a valid and reliable test for discriminating between dementia and CI sufferers and subjects with no CI. Its validity is similar to that of the MMSE under these conditions, but it is more effective for identifying subjects with MCI and its administration time is shorter. Resumen: Antecedentes: En los próximos 20 años se duplicará la cantidad de personas con deterioro cognitivo (DC) apremiando su pronta detección. Objetivos: Validar una prueba de cribado de DC aplicable en < de 5 minutos. Métodos: Adultos ≥60 años reclutados desde la comunidad y clínicas de memoria de la zona urbana de Santiago de Chile fueron clasificados clínicamente en: Dementes, DC leve (DCL) y Sin DC (SDC). Se evaluó la validez de un nuevo test: MEFO, consistente en la evaluación de: Memoria (5 puntos), Fluidez Fonética (2 puntos) y Orientación (6 puntos) contrastado con los resultados del MMSE. Resultados: Se evaluaron 214 personas: 49 con demencia, 47 con DCL y 118 SDC. El MEFO diferenció a los 3 grupos clínicos entre sí, mientras que el MMSE no permitió discriminar DCL de SDC. El área bajo la curva ROC en el MEFO para diferenciar los grupos SDC versus: i: Demencia fue = 0,97; ii: DC (dementes + DCL)fue = 0,89; y iii: DCL fue = 0,80; siendo estos valores para el MMSE de 0,95, 0,84, y 0,73, respectivamente. Un punto de corte (PC) del MEFO = 6/7 distinguió a las personas con demencia con una sensibilidad (S) = 86% y especificidad (E) = 96%; y un PC = 8/9 distinguió a aquellos con DC con una: S = 83% y E = 75%. Conclusiones: El MEFO resultó una prueba confiable y válida para diferenciar a personas con demencia y DC, similar al MMSE en éstos casos, pero con mayor utilidad para distinguir a los pacientes con DCL y de menor duración de aplicación. Keywords: Cognitive impairment screening, Chile, Dementia, Spanish, Palabras clave: Cribado de deterioro cognitivo, Chile, Demencias, Español

Global initiatives call for further understanding of the impact of inequity on aging across underserved populations. Previous research in low- and middle-income countries (LMICs) presents limitations in assessing combined sources of inequity and outcomes (i.e., cognition and functionality). In this study, we assessed how social determinants of health (SDH), cardiometabolic factors (CMFs), and other medical/social factors predict cognition and functionality in an aging Colombian population. We ran a cross-sectional study that combined theory- (structural equation models) and data-driven (machine learning) approaches in a population-based study (N = 23,694; M = 69.8 years) to assess the best predictors of cognition and functionality. We found that a combination of SDH and CMF accurately predicted cognition and functionality, although SDH was the stronger predictor. Cognition was predicted with the highest accuracy by SDH, followed by demographics, CMF, and other factors. A combination of SDH, age, CMF, and additional physical/psychological factors were the best predictors of functional status. Results highlight the role of inequity in predicting brain health and advancing solutions to reduce the cognitive and functional decline in LMICs.

BackgroundCOVID-19-related restrictions led to an increase in overall loneliness and social isolation. Before the pandemic, care partners reported higher levels of loneliness and higher loneliness prevalence compared to non-care partners. Because of the spread and severity of the infections, and the access to support spread, we expect a different impact of the COVID-19 pandemic on LATAM care partners.ObjectivesTo describe the loneliness levels of LATAM caregivers and to identify socioeconomic and health factors associated.DesignAn international online cross-sectional survey for care partners, embedded within the ‘Coping with Loneliness and Isolation during COVID-19’ (CLIC) Study conducted between June 2020– and November 2020.SettingWe analysed data from 246 family care partners living in Latin American countries (46% Mexico, 26% Chile,18% Brazil, and 10% from Argentina, Peru, Venezuela, Panama, Guatemala y Costa Rica).MeasurementsWe assessed loneliness using the 6-items of De Jong Gierveld loneliness Scale. We described the levels of overall, emotional, and social loneliness pre and during Covid, and reported the distribution of care partners who improved, worsened or maintained their levels of loneliness. Moreover, we used longitudinal multiple linear regression models with bootstraps errors of 1,000 iterations to identify factors associated with the levels of overall, emotional, and social loneliness during the pandemic.ResultsParticipants were mostly women, 50 years and older, in a partnership, highly educated and with finances meeting their needs, with good to excellent physical and mental health. Among the total of care partners, 55% perceived higher overall loneliness, 56% higher emotional loneliness, and 21% higher social loneliness during the pandemic in comparison with pre-COVID-19 levels. Perceived mental health was associated with the overall, emotional, and social loneliness.ConclusionsRegardless of their living and health situation, during the pandemic, loneliness increased in all groups of care partners. These should be taken in consideration when planning public health approaches for crises such as pandemics or other large-scale disruptive events.

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.

BackgroundGlobal brain health initiatives call for improving methods for the diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) in underrepresented populations. However, diagnostic procedures in upper-middle-income countries (UMICs) and lower-middle income countries (LMICs), such as Latin American countries (LAC), face multiple challenges. These include the heterogeneity in diagnostic methods, lack of clinical harmonisation, and limited access to biomarkers.MethodsThis cross-sectional observational study aimed to identify the best combination of predictors to discriminate between AD and FTD using demographic, clinical and cognitive data among 1794 participants [904 diagnosed with AD, 282 diagnosed with FTD, and 606 healthy controls (HCs)] collected in 11 clinical centres across five LAC (ReDLat cohort).FindingsA fully automated computational approach included classical statistical methods, support vector machine procedures, and machine learning techniques (random forest and sequential feature selection procedures). Results demonstrated an accurate classification of patients with AD and FTD and HCs. A machine learning model produced the best values to differentiate AD from FTD patients with an accuracy = 0.91. The top features included social cognition, neuropsychiatric symptoms, executive functioning performance, and cognitive screening; with secondary contributions from age, educational attainment, and sex.InterpretationResults demonstrate that data-driven techniques applied in archival clinical datasets could enhance diagnostic procedures in regions with limited resources. These results also suggest specific fine-grained cognitive and behavioural measures may aid in the diagnosis of AD and FTD in LAC. Moreover, our results highlight an opportunity for harmonisation of clinical tools for dementia diagnosis in the region.FundingThis work was supported by the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat), funded by NIA/NIH (R01AG057234), Alzheimer's Association (SG-20-725707-ReDLat), Rainwater Foundation, Takeda (CW2680521), Global Brain Health Institute; as well as CONICET; FONCYT-PICT (2017-1818, 2017-1820); PIIECC, Facultad de Humanidades, Usach; Sistema General de Regalías de Colombia (BPIN2018000100059), Universidad del Valle (CI 5316); ANID/FONDECYT Regular (1210195, 1210176, 1210176); ANID/FONDAP (15150012); ANID/PIA/ANILLOS ACT210096; and Alzheimer's Association GBHI ALZ UK-22-865742.

Latin American and Caribbean countries face complex challenges to improve brain health and reduce the impact of dementia. Regional hubs devoted to research, capacity building, implementation science, and education are critically needed. The Latin American Brain Health Institute represent an important step to address many of these needs.

Objective.The differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) and Alzheimers disease (AD) remains challenging in underrepresented, underdiagnosed groups, including Latinos, as advanced biomarkers are rarely available. Recent guidelines for the study of dementia highlight the critical role of biomarkers. Thus, novel cost-effective complementary approaches are required in clinical settings.Approach. We developed a novel framework based on a gradient boosting machine learning classifier, tuned by Bayesian optimization, on a multi-feature multimodal approach (combining demographic, neuropsychological, magnetic resonance imaging (MRI), and electroencephalography/functional MRI connectivity data) to characterize neurodegeneration using site harmonization and sequential feature selection. We assessed 54 bvFTD and 76 AD patients and 152 healthy controls (HCs) from a Latin American consortium (ReDLat).Main results. The multimodal model yielded high area under the curve classification values (bvFTD patients vs HCs: 0.93 (±0.01); AD patients vs HCs: 0.95 (±0.01); bvFTD vs AD patients: 0.92 (±0.01)). The feature selection approach successfully filtered non-informative multimodal markers (from thousands to dozens).Results. Proved robust against multimodal heterogeneity, sociodemographic variability, and missing data.Significance. The model accurately identified dementia subtypes using measures readily available in underrepresented settings, with a similar performance than advanced biomarkers. This approach, if confirmed and replicated, may potentially complement clinical assessments in developing countries.

Abstract The Latin American Brain Health Institute (BrainLat) has released a unique multimodal neuroimaging dataset of 780 participants from Latin American. The dataset includes 530 patients with neurodegenerative diseases such as Alzheimer’s disease (AD), behavioral variant frontotemporal dementia (bvFTD), multiple sclerosis (MS), Parkinson’s disease (PD), and 250 healthy controls (HCs). This dataset (62.7 ± 9.5 years, age range 21–89 years) was collected through a multicentric effort across five Latin American countries to address the need for affordable, scalable, and available biomarkers in regions with larger inequities. The BrainLat is the first regional collection of clinical and cognitive assessments, anatomical magnetic resonance imaging (MRI), resting-state functional MRI (fMRI), diffusion-weighted MRI (DWI), and high density resting-state electroencephalography (EEG) in dementia patients. In addition, it includes demographic information about harmonized recruitment and assessment protocols. The dataset is publicly available to encourage further research and development of tools and health applications for neurodegeneration based on multimodal neuroimaging, promoting the assessment of regional variability and inclusion of underrepresented participants in research.

INTRODUCTION: Automated speech analysis has emerged as a scalable, cost-effective tool to identify persons with Alzheimers disease dementia (ADD). Yet, most research is undermined by low interpretability and specificity. METHODS: Combining statistical and machine learning analyses of natural speech data, we aimed to discriminate ADD patients from healthy controls (HCs) based on automated measures of domains typically affected in ADD: semantic granularity (coarseness of concepts) and ongoing semantic variability (conceptual closeness of successive words). To test for specificity, we replicated the analyses on Parkinsons disease (PD) patients. RESULTS: Relative to controls, ADD (but not PD) patients exhibited significant differences in both measures. Also, these features robustly discriminated between ADD patients and HC, while yielding near-chance classification between PD patients and HCs. DISCUSSION: Automated discourse-level semantic analyses can reveal objective, interpretable, and specific markers of ADD, bridging well-established neuropsychological targets with digital assessment tools.

The prevalence of dementia in Latin America and the Caribbean is growing rapidly, increasing the burden placed on caregivers. Exacerbated by fragile health-care systems, unstable economies, and extensive inequalities, caregiver burden in this region is among the highest in the world. We reviewed the major challenges to caregiving in Latin America and the Caribbean, and we propose regional and coordinated actions to drive future change. Current challenges include the scarcity of formal long-term care, socioeconomic and social determinants of health disparities, gender-biased burdens, growing dementia prevalence, and the effect of the current COVID-19 pandemic on families affected by dementia. Firstly, we propose local and regional short-term strategic recommendations, including systematic identification of specific caregiver needs, testing of evidence-based local interventions, contextual adaptation of strategies to different settings and cultures, countering gender bias, strengthening community support, provision of basic technology, and better use of available information and communications technology. Additionally, we propose brain health diplomacy (ie, global actions aimed to overcome the systemic challenges to brain health by bridging disciplines and sectors) and convergence science as frameworks for long-term coordinated responses, integrating tools, knowledge, and strategies to expand access to digital technology and develop collaborative models of care. Addressing the vast inequalities in dementia caregiving across Latin America and the Caribbean requires innovative, evidence-based solutions coordinated with the strengthening of public policies.

ABSTRACT Rowland Universal Dementia Assessment Scale (RUDAS) is a cognitive screening that evaluates older people with low educational levels. In Chile, there are no normative data to assess this population. Objective: To obtain normative data on RUDAS in older Chilean people with up to 12 years of schooling, and to determine whether age and schooling years influence a person’s performance on RUDAS and on the items that constitute it. Methods: A group of cognitively healthy people 60 years old or over, with up to 12 schooling years was evaluated (n=135). Multiple regression models were applied to obtain normative data on RUDAS, according to age and schooling years, and to measure the effects of schooling on different items. Results: Regression analysis showed that none of the items had schooling as a significant predictor, except for the visuoconstruction item. The variables age and schooling explained 12.6% (R^2=0.126) of the RUDAS total score variance. The item visuoconstruction was the most associated with the educational level (OR=1,147). Conclusion: This study showed that RUDAS is a recommended instrument for evaluating older people with low educational levels. However, more studies are needed to prove the validity of the RUDAS on Chilean older people.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.

Frontotemporal dementia (FTD) includes a group of clinically, genetically, and pathologically heterogeneous neurodegenerative disorders, affecting the fronto-insular-temporal regions of the brain. Clinically, FTD is characterized by progressive deficits in behavior, executive function, and language and its diagnosis relies mainly on the clinical expertise of the physician/consensus group and the use of neuropsychological tests and/or structural/functional neuroimaging, depending on local availability. The modest correlation between clinical findings and FTD neuropathology makes the diagnosis difficult using clinical criteria and often leads to underdiagnosis or misdiagnosis, primarily due to lack of recognition or awareness of FTD as a disease and symptom overlap with psychiatric disorders. Despite advances in understanding the underlying neuropathology of FTD, accurate and sensitive diagnosis for this disease is still lacking. One of the major challenges is to improve diagnosis in FTD patients as early as possible. In this context, biomarkers have emerged as useful methods to provide and/or complement clinical diagnosis for this complex syndrome, although more evidence is needed to incorporate most of them into clinical practice. However, most biomarker studies have been performed using North American or European populations, with little representation of the Latin American and the Caribbean (LAC) region. In the LAC region, there are additional challenges, particularly the lack of awareness and knowledge about FTD, even in specialists. Also, LAC genetic heritage and cultures are complex, and both likely influence clinical presentations and may modify baseline biomarker levels. Even more, due to diagnostic delay, the clinical presentation might be further complicated by both neurological and psychiatric comorbidity, such as vascular brain damage, substance abuse, mood disorders, among others. This systematic review provides a brief update and an overview of the current knowledge on genetic, neuroimaging, and fluid biomarkers for FTD in LAC countries. Our review highlights the need for extensive research on biomarkers in FTD in LAC to contribute to a more comprehensive understanding of the disease and its associated biomarkers. Dementia research is certainly reduced in the LAC region, highlighting an urgent need for harmonized, innovative, and cross-regional studies with a global perspective across multiple areas of dementia knowledge.

Dementia is becoming increasingly prevalent in Latin America, contrasting with stable or declining rates in North America and Europe. This scenario places unprecedented clinical, social, and economic burden upon patients, families, and health systems. The challenges prove particularly pressing for conditions with highly specific diagnostic and management demands, such as frontotemporal dementia. Here we introduce a research and networking initiative designed to tackle these ensuing hurdles, the Multi-partner consortium to expand dementia research in Latin America (ReDLat). First, we present ReDLat's regional research framework, aimed at identifying the unique genetic, social, and economic factors driving the presentation of frontotemporal dementia and Alzheimer's disease in Latin America relative to the US. We describe ongoing ReDLat studies in various fields and ongoing research extensions. Then, we introduce actions coordinated by ReDLat and the Latin America and Caribbean Consortium on Dementia (LAC-CD) to develop culturally appropriate diagnostic tools, regional visibility and capacity building, diplomatic coordination in local priority areas, and a knowledge-to-action framework toward a regional action plan. Together, these research and networking initiatives will help to establish strong cross-national bonds, support the implementation of regional dementia plans, enhance health systems' infrastructure, and increase translational research collaborations across the continent.

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.

IntroductionExpert knowledge is critical to fight dementia in inequitable regions like Latin American and Caribbean countries (LACs). However, the opinions of aging experts on public policies' accessibility and transmission, stigma, diagnostic manuals, data-sharing platforms, and use of behavioral insights (BIs) are not well known.MethodsWe investigated opinions among health professionals working on aging in LACs (N = 3365) with regression models including expertise-related information (public policies, BI), individual differences (work, age, academic degree), and location.ResultsExperts specified low public policy knowledge (X2  = 41.27, P

Background: Most research initiatives have emerged from high‐income countries (HIC), leaving a gap in understanding the disease's genetic basis in diverse populations like those in Latin American countries (LAC). ReDLat tackles this gap, focusing on LAC's unique genetics and socioeconomic factors to identify specific Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD) risk factors in Mexico, Colombia, Peru, Chile, Argentina, and Brazil. Method: We employed a comprehensive genetic analysis approach, integrating Whole Genome Sequencing (WGS), Exome Sequencing, and SNP arrays to understand the cohort's unique genetic architecture. We conducted ancestry analysis and searched for disease‐causing variants with mendelian inheritance, genome‐wide association studies (GWAS), rare variant enrichment, and evaluation of Polygenic Risk Scores (PRS). Results: We recruited and genotyped an initial cohort of 1046 participants with AD, 423 with FTD, and 855 healthy controls (HC) between 2020 and 2023. Analysis is ongoing, and we expect to sequence ∼600 additional samples in the coming months. Ancestry analysis revealed tri‐continental admixture, except for Brazil, which showed an additional Asian component (Figure 1). Top candidate gene rare variant enrichment associations (SKAT p < 0.05) were TREM2 for FTD and ABCA7 and ABCA1 for AD. GWAS identified a robust association with the APOE locus on chromosome 19 in AD vs. HC.. We tested an AD PRS developed in European populations by Bellenguez et al (2020). on our cohort using 83 single‐nucleotide polymorphisms.. The PRS modestly distinguishes between all patients and HC (p = 2.4 × 10^‐12), AD vs. HC (p = 2.2 × 10^‐12), and even FTD vs. HC (p = 4.3 × 10^‐5), albeit with modest separation between groups, as expected for its application in a genetically admixed population. Conclusion: Our findings represent a pivotal step in understanding the genetic landscape of AD and FTD in admixed populations. They underscore the importance of including diverse populations in genetic research, paving the way for future studies. These findings have the potential to inform more personalized approaches to the diagnosis and treatment of neurodegenerative diseases in diverse global populations, as well as identify novel targets for therapeutic development. [ABSTRACT FROM AUTHOR]

Background: The most common and prevalent dementia worldwide is Alzheimer's disease (AD). AD is a continuum composed of Subjective Cognitive Impairment (SCD), Mild Cognitive Impairment (MCI), and Alzheimer's Disease dementia (ADD) stage. One of the main clinical variables in patients with dementia is performance in functional capacity since its alterations are associated with poor prognosis and disease progression. Functional capacity is measured through activities of daily living (ADL), which are divided into three domains: i) Basic (BADL), ii) Instrumental (IADL), and iii) Advanced (AADL). The study aimed to characterize the performance of the different stages of the AD continuum in the ADL domains and their association with cognitive abilities. Method: A cross‐sectional study of subjects at different stages of the AD continuum was conducted: Healthy Controls (CTR) (n = 17), SCD (n = 77), MCI (n = 30), and ADD (n = 23), who were matched for age, sex, and education. ADLs were estimated using The Technology‐Activities of Daily Living Questionnaire (T‐ADLQ), which assesses the three domains and a total score. T‐ADLQ performance was compared across groups and correlated with cognitive ability instruments (ACE‐III and IFS). Result: The results showed that patients with ADD performed worse on the BADL, IADL, and total ADLs compared to the other three groups. There were no significant differences between the CTR, SCD, and MCI on the BADL, IADL, and total ADLs. However, the AADL, in addition to differentiating the ADD patients from the other three groups, also showed differences between CTR and MCI subjects and between SCD and MCI subjects (Table 1 and Figure 1). The correlation study showed that AADL correlated significantly with global cognitive and executive function assessment (Figure 2). Conclusion: AADL shows progressive functional impairment at different stages of the AD continuum, which is further associated with global cognitive and executive function performances. As one progresses to a more advanced stage of the disease continuum, the performance of ADLs, especially AADLs, worsens, which could indicate a marker of disease progression, allowing for better patient follow‐up. [ABSTRACT FROM AUTHOR]

Background: COVID-19-related restrictions led to an increase in overall loneliness and social isolation. Before the pandemic, care partners reported higher levels of loneliness and higher loneliness prevalence compared to non-care partners. Because of the spread and severity of the infections, and the access to support spread, we expect a different impact of the COVID-19 pandemic on LATAM care partners. Objectives: To describe the loneliness levels of LATAM caregivers and to identify socioeconomic and health factors associated. Design: An international online cross-sectional survey for care partners, embedded within the 'Coping with Loneliness and Isolation during COVID-19' (CLIC) Study conducted between June 2020– and November 2020. Setting: We analysed data from 246 family care partners living in Latin American countries (46% Mexico, 26% Chile,18% Brazil, and 10% from Argentina, Peru, Venezuela, Panama, Guatemala y Costa Rica). Measurements: We assessed loneliness using the 6-items of De Jong Gierveld loneliness Scale. We described the levels of overall, emotional, and social loneliness pre and during Covid, and reported the distribution of care partners who improved, worsened or maintained their levels of loneliness. Moreover, we used longitudinal multiple linear regression models with bootstraps errors of 1,000 iterations to identify factors associated with the levels of overall, emotional, and social loneliness during the pandemic. Results: Participants were mostly women, 50 years and older, in a partnership, highly educated and with finances meeting their needs, with good to excellent physical and mental health. Among the total of care partners, 55% perceived higher overall loneliness, 56% higher emotional loneliness, and 21% higher social loneliness during the pandemic in comparison with pre-COVID-19 levels. Perceived mental health was associated with the overall, emotional, and social loneliness. Conclusions: Regardless of their living and health situation, during the pandemic, loneliness increased in all groups of care partners. These should be taken in consideration when planning public health approaches for crises such as pandemics or other large-scale disruptive events. [ABSTRACT FROM AUTHOR]

Background: Cognitive complaints (CC) refer to a reported experience of cognitive decline and are recognized as a potential precursor to future functional decline and progression to dementia. Identifying individuals with CC may be a valuable opportunity for preventive measures, early detection, and intervention strategies to address dementia risk. However, the characteristics of CC and its associated risk of progression to dementia are highly heterogeneous, influenced significantly by CC identification methods, recruitment approaches, and attrition in longitudinal cohort studies. This study aims to inform the inclusion and attrition processes of the GERO cohort. Method: The GERO cohort is a prospective cohort study of community‐dwelling elderly individuals with CC without dementia, aged 70 or older, living in Santiago, Chile. In this study, two samples were analyzed (dropout and non‐dropout groups) using logistic regression to assess the variables associated with attrition. Binary logistic regression analyses were conducted with dropout as the outcome variable. Prior to the multivariable models, univariate analyses were performed. Result: Out of 17,759 households approached, we successfully recruited 291 participants. Of the individuals initially recruited, 102 participants withdrew before the first follow‐up assessment. The results showed that the non‐dropout group (64.9%) was characterized by being younger (OR: 1.09; 95% CI: 1.04‐1.14), had better cognitive status according to the MoCA test (OR: 0.92; 95% CI: 0.87‐0.98), had better functionality according to the T‐ADLQ (OR: 1.08; 95% CI: 1.04‐1.12), better performance in instrumental ‐IADL‐ (OR: 1.06; 95% CI: 1.03‐1.09) and advanced ‐aADL‐ (OR: 1.03; 95% CI: 1.01‐1.04) dimensions, and better performance on the ECOG test (OR: 2.56; 95% CI: 1.13‐4.53) compared to the dropout group (35.1%). In the multivariate logistic regression model, dropout was associated with the performance of instrumental activities of daily living IADL (OR: 1.05; 95% CI: 1.01‐1.09), whereas the other variables did not exhibit statistical significance (Table 1). Conclusion: The rate of participants included, considering the number of households approached, inform on the difficulties to recruit participants with CC in the community. Functionality in daily life emerged as the key factor associated with the risk of dropout. Furthers research is needed to understand the role of functionality in CC. [ABSTRACT FROM AUTHOR]

Frente a las brechas de acceso a la educación superior, el Gobierno de Chile creó el 2014 un programa de acción afirmativa con el objetivo de restituir el derecho a ese ni- vel educativo: el Programa de Acompañamiento y Acceso Efectivo a la Educación Superior (PACE). A siete años de su implementación, este estudio analiza los principios ligados a la acción afirmativa, que dan origen al programa, junto a la transformación de sus alcances y sustentos, argumentando que existiría una contradicción entre la acción afirmativa y el propósito explícitamente declarado de la restitución de un derecho social. Dentro del mismo análisis, se postula que la evolución de ciertos criterios de focalización podría dar cuenta de una inflexión desde el paradigma neoliberal hacia un nuevo paradigma de lo público. Para estos efectos, el estudio propone un análisis de documentos gubernamentales desde una perspectiva socio-histórica de la política, pudiendo aportar a las decisiones educativas dentro del contexto político nacional y latinoamericano.