Brain clocks capture diversity and disparity in aging and dementia.

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

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.

A Multidimensional, Person-Centered Framework for Functional Assessment in Dementia: Insights from the 'What', 'How', 'To Whom', and 'How Much' Questions.

Dementia is a syndrome characterized by cognitive and neuropsychiatric symptoms associated with progressive functional decline (FD). FD is a core diagnostic criterion for dementia, setting the threshold between its prodromal stages and the full-blown disease. The operationalization of FD continues to generate a great deal of controversy. For instance, the threshold of FD for the diagnosis of dementia varies across diagnostic criteria, supporting the need for standardization of this construct. Moreover, there is a need to reconsider how we are measuring FD to set boundaries between normal aging, mild cognitive impairment, and dementia. In this paper, we propose a multidimensional framework that addresses outstanding issues in the assessment of FD: i) What activities of daily living (ADLs) are necessary to sustain an independent living in aging? ii) How to assess FD in individuals with suspected neurocognitive disorders? iii) To whom is the assessment directed? and iv) How much does FD differentiate healthy aging from mild and major neurocognitive disorders? Importantly, the To Whom Question introduces a person-centered approach that regards patients and caregivers as active agents in the assessment process of FD. Thus, once impaired ADLs have been identified, patients can indicate how significant such impairments are for them in daily life. We envisage that this new framework will guide future strategies to enhance functional assessment and treatment of patients with dementia and their caregivers.

Brain health in diverse settings: How age, demographics and cognition shape brain function.

Diversity in brain health is influenced by individual differences in demographics and cognition. However, most studies on brain health and diseases have typically controlled for these factors rather than explored their potential to predict brain signals. Here, we assessed the role of individual differences in demographics (age, sex, and education; n = 1298) and cognition (n = 725) as predictors of different metrics usually used in case-control studies. These included power spectrum and aperiodic (1/f slope, knee, offset) metrics, as well as complexity (fractal dimension estimation, permutation entropy, Wiener entropy, spectral structure variability) and connectivity (graph-theoretic mutual information, conditional mutual information, organizational information) from the source space resting-state EEG activity in a diverse sample from the global south and north populations. Brain-phenotype models were computed using EEG metrics reflecting local activity (power spectrum and aperiodic components) and brain dynamics and interactions (complexity and graph-theoretic measures). Electrophysiological brain dynamics were modulated by individual differences despite the varied methods of data acquisition and assessments across multiple centers, indicating that results were unlikely to be accounted for by methodological discrepancies. Variations in brain signals were mainly influenced by age and cognition, while education and sex exhibited less importance. Power spectrum activity and graph-theoretic measures were the most sensitive in capturing individual differences. Older age, poorer cognition, and being male were associated with reduced alpha power, whereas older age and less education were associated with reduced network integration and segregation. Findings suggest that basic individual differences impact core metrics of brain function that are used in standard case-control studies. Considering individual variability and diversity in global settings would contribute to a more tailored understanding of brain function.

Short-term memory binding is insensitive to the socioeconomic status of older adults with and without mild cognitive impairment.

Objective: The Visual Short-Term Memory Binding (VSTMB) Test is a useful tool in the assessment of Alzheimer's disease (AD). Research has suggested that short-term memory binding is insensitive to the sociocultural characteristics of the assessed individuals. Such earlier studies addressed this influence by considering years of education. The current study aims to determine the influence of sociocultural factors via a measure of Socioeconomic Status (SES) which provides a more holistic approach to these common confounders. Methods: A sample of 126 older adults, both with (n = 59) and without (n = 67) amnestic mild cognitive impairment (aMCI), underwent assessment using a neuropsychological protocol including VSTMB test. All participants were classified as either high SES or low SES, employing the Standard Demographic Classification from the European Society for Opinion and Marketing Research. Results: ANOVA/ANCOVA models confirmed that performance of healthy and aMCI participants on traditional neuropsychological tests were sensitive to SES whereas the VSTMB Test was not. The results add to the growing array of evidence suggesting that there are cognitive abilities which are unaffected by socioeconomic factors, regardless of clinical condition. Conclusions: The lack of sensitivity to sociocultural factors previously reported for the VSTMB test is accompanied by a lack of sensitivity to socioeconomic factors thus broadening the scope of this test to aid in the detection of dementia across populations with different backgrounds. Future studies should take these findings forward and explore the potential influences of AD biomarkers (A/T/N) on the association between cognitive functions and demographic variables.

Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole-brain modeling.

INTRODUCTION: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost-effective technique for studying dementia globally, but lacks mechanistic models and produces non-replicable results. METHODS: We developed a generative whole-brain model that combines EEG source-level metaconnectivity, anatomical priors, and a perturbational approach. This model was applied to Global South participants (AD, bvFTD, and healthy controls). RESULTS: Metaconnectivity outperformed pairwise connectivity and revealed more viscous dynamics in patients, with altered metaconnectivity patterns associated with multimodal disease presentation. The biophysical model showed that connectome disintegration and hypoexcitability triggered altered metaconnectivity dynamics and identified critical regions for brain stimulation. We replicated the main results in a second subset of participants for validation with unharmonized, heterogeneous recording settings. DISCUSSION: The results provide a novel agenda for developing mechanistic model-inspired characterization and therapies in clinical, translational, and computational neuroscience settings.

Characterization of the genetic diversity, structure, and admixture of 7 Chilean chicken breeds.

The Mapuche fowl is an autochthonous breed raised in Chile and represents an important zoogenetic resource for the local economy. This study aimed at investigating the genetic diversity, relationship and population structure of 96 local Chilean chickens derived from 3 ecotype of Mapuche fowl (Kollonka, Ketro, and Kollonka de aretes), 2 ecotype Chilean (Trintre, Cogote pelado) and 2 breeds (Light Brahma and Barred Plymouth Rock) using 12 microsatellite markers. In total, 113 alleles were detected in all populations, with a mean of 7.6 alleles per population. In all population chicken breeds, the observed and expected heterozygosity ranged from 0.91 to 0.98 and from 0.69 to 0.79. Furthermore, all populations showed significant deviations from Hardy-Weinberg expectations. Across each population, the global heterozygosity deficit (FIT) was -0.174, population differentiation index (FST) was 0.073, and the global inbreeding of individuals within breed (FIS) was -0.267. The phylogenetic relationships of chickens were examined using neighbor-joining trees constructed at the level of population. The highest Nei's standard genetic distance value of 0.559 was observed between Barred Plymouth Rock and Light Brahma, whereas the minimum value (0.099) was found between Kollonka and Trintre. The neighbor-joining tree constructed at population level revealed 2 main clusters, with Light Brahma, Barred Plymouth Rock, Ketro and Kollonka de aretes in 1 cluster, and Kollonka, Trintre and Cogote pelado breeds in the second cluster. Based on the results of the STRUCTURE analysis, the most likely number of clustering of the population evaluated was at K = 3, with Light Brahma and Barred Plymouth Rock breeds forming their own distinct clusters, while Kollonka, Ketro, Kollonka de aretes, Trintre and Cogote pelado breeds clustered together. This study represents the first report of genetic diversity in these populations in Chile. These results can be used as baseline genetic information for genetic conservation program, for instance, to control inbreeding and to implement further genetic studies in local Chilean chickens.

The BrainLat project, a multimodal neuroimaging dataset of neurodegeneration from underrepresented backgrounds.

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.

Assessing attentional bias to emotions in adolescent offenders and nonoffenders.

Emotional processing is a cognitive function essential for the interaction of humans with their environment and the development of adaptive behaviors. Adolescent offenders (AOs) express difficulty in cognitive processes linked to emotional processing, which is a response consistently observed during the endogenous (i.e., controlled) control of attention. Less remains understood of the extent to which such atypical responses extend beyond controlled attention and influence exogenous mechanisms (i.e., automatic). This study explores this hypothesis using the recently devised emotional Flanker paradigm. It recruited a group of 39 male AOs and 39 nonoffenders from Barranquilla, Colombia. Assessment consists of an emotional Flanker paradigm administered along with traditional neurocognitive and social cognition tasks. The AOs displayed the well-known attentional bias to threat and a relatively atypical response to emotional targets in which they detected emotions, particularly negative ones, faster than did nonoffenders. Frontal lobe functions account for these effects but not sociodemographic variables nor general cognitive abilities. The results are interpreted in light of evidence suggesting that youngsters with high levels of antisocial behaviors (e.g., callous-unemotional traits) present an enhanced orientation toward distressing stimuli, which is explained by lifelong experiences (e.g., histories of abuse). The findings suggest that environmental influences seemingly exist in the development of these traits, but additional research is required to elucidate the role of cognitive and environmental factors in the development of antisocial behavior.

Eficacia y seguridad de la combinación de dosis fija montelukast-desloratadina 10 mg/5 mg cápsula en adultos mexicanos con rinitis alérgica persistente: Estudio controlado, aleatorizado, doble ciego y multicéntrico / Efficacy and safety of fixed-dose combination of montelukast-desloratadine 10 mg/5 mg capsule in Mexican adults with persistent allergic rhinitis: A double blind, randomized, controlled and multicenter study

Objetivo: El objetivo del presente estudio fue evaluar la eficacia y seguridad de la combinación de dosis fija montelukast/desloratadina 10mg/5mg cápsula versus la combinación de montelukast/loratadina 10 mg/10 mg tableta en adultos con diagnóstico de rinitis alérgica persistente. Material y métodos: El presente fue un estudio clínico aleatorizado, controlado, doble ciego, prospectivo, longitudinal, multicéntrico, con brazos paralelos. Sujetos con diag nóstico de rinitis alérgica persistente que cumplieran criterios de elegibilidad y firmaran consentimiento informado fueron enrolados para recibir uno de los dos tratamientos cada 24 horas vía oral durante 6 semanas. La eficacia se estableció mediante la evaluación clínica a través de escalas clínicas validadas en idioma español, siendo la variable primaria de eficacia la diferencia de puntuación del cuestionario SNOT-20 al final del tratamiento, mientras que la frecuencia y características de los eventos adversos fue considerada la variable de seguridad. Resultados: Se aleatorizaron 86 pacientes, 74 de ellos fueron analizados por protocolo. Los cuestionarios sobre síntomas de la enfermedad e indicadores de calidad de vida con ambos tratamientos mostraron que más del 90% de los pacientes no presentaron síntomas o solo fueron leves al final del estudio, por lo que ambos tratamientos me joraron significativamente (p < 0.05) la sintomatología de la enfermedad. Los eventos adversos presentados fueron leves a moderados. Conclusiones: El presente estudio demostró que la eficacia de montelukast/deslora tadina 10mg/5mg no es inferior al medicamento comparador. Por tanto, el tratamiento de prueba representa una alternativa eficaz y segura para el tratamiento de segunda línea de la rinitis alérgica persistente en pacientes que las monoterapias o primeras líneas de tratamiento no ofrecen mejoría clínicamente relevante.

Objective: The objective of the present study was to evaluate the efficacy and safety of the fixed dose combination of montelukast/desloratadine 10 mg/5 mg capsule versus the combination of montelukast/loratadine 10 mg/10 mg tablet in adults diagnosed with persistent allergic rhinitis. Materials and methods: The present study was a multicenter, controlled, prospective, longitudinal, randomized, double-blind clinical trial with parallel arms. Patients diagnosed with persistent allergic rhinitis who met eligibility criteria and signed informed consent were enrolled in the study to receive one of the two treatments every 24 hours orally for 6 weeks. Efficacy was established by clinical evaluation through clinical scales vali dated in Spanish, being the primary efficacy variable the difference in the score of the SNOT-20 (Sino-Nasal Outcome Test) questionnaire at the end of treatment; and the frequency and characteristics of adverse events were considered the safety variable. Results: 86 patients were randomized, 74 of which were analyzed per protocol. Ques tionnaires about the symptoms of the disease and quality of life indicators with both treatments showed that more than 90% of patients had mild symptoms or no symptoms at all at the end of the study. So, both treatments significantly improved (p < 0.05) the symptoms of the disease. Adverse events were mild to moderate. Conclusions: The present study showed that the efficacy of montelukast/desloratadine 10 mg/5 mg is not inferior to the comparator. Therefore, the study treatment represents an effective and safe alternative for the second-line treatment of persistent allergic rhinitis in patients in whom monotherapies or first-line treatments don't offer clinically relevant improvement.

The limitations and challenges in the assessment of executive dysfunction associated with real-world functioning: The opportunity of serious games.

Nowadays, there is a broad range of methods for detecting and evaluating executive dysfunction ranging from clinical interview to neuropsychological evaluation. Nevertheless, a critical issue of these assessments is the lack of correspondence of the neuropsychological test's results with real-world functioning. This paper proposes serious games as a new framework to improve the neuropsychological assessment of real-world functioning. We briefly discuss the contribution and limitations of current methods of evaluation of executive dysfunction (paper-and-pencil tests, naturalistic observation methods, and Information and Communications Technologies) to inform on daily life functioning. Then, we analyze what are the limitations of these methods to predict real-world performance: (1) A lack of appropriate instruments to investigate the complexity of real-world functioning, (2) the vast majority of neuropsychological tests assess well-structured tasks, and (3) measurement of behaviors are based on simplistic data collection and statistical analysis. This work shows how serious games offer an opportunity to develop more efficient tools to detect executive dysfunction in everyday life contexts. Serious games provide meaningful narrative stories and virtual or real environments that immerse the user in natural and social environments with social interactions. In those highly interactive game environments, the player needs to adapt his/her behavioral performance to novel and ill-structured tasks which are suited for collecting user interaction evidence. Serious games offer a novel opportunity to develop better tools to improve diagnosis of the executive dysfunction in everyday life contexts. However, more research is still needed to implement serious games in everyday clinical practice.

Source space connectomics of neurodegeneration: One-metric approach does not fit all.

Brain functional connectivity in dementia has been assessed with dissimilar EEG connectivity metrics and estimation procedures, thereby increasing results' heterogeneity. In this scenario, joint analyses integrating information from different metrics may allow for a more comprehensive characterization of brain functional interactions in different dementia subtypes. To test this hypothesis, resting-state electroencephalogram (rsEEG) was recorded in individuals with Alzheimer's Disease (AD), behavioral variant frontotemporal dementia (bvFTD), and healthy controls (HCs). Whole-brain functional connectivity was estimated in the EEG source space using 101 different types of functional connectivity, capturing linear and nonlinear interactions in both time and frequency-domains. Multivariate machine learning and progressive feature elimination was run to discriminate AD from HCs, and bvFTD from HCs, based on joint analyses of i) EEG frequency bands, ii) complementary frequency-domain metrics (e.g., instantaneous, lagged, and total connectivity), and iii) time-domain metrics with different linearity assumption (e.g., Pearson correlation coefficient and mutual information). <10% of all possible connections were responsible for the differences between patients and controls, and atypical connectivity was never captured by >1/4 of all possible connectivity measures. Joint analyses revealed patterns of hypoconnectivity (patientsHCs) in both groups was mainly identified in frontotemporal regions. These atypicalities were differently captured by frequency- and time-domain connectivity metrics, in a bandwidth-specific fashion. The multi-metric representation of source space whole-brain functional connectivity evidenced the inadequacy of single-metric approaches, and resulted in a valid alternative for the selection problem in EEG connectivity. These joint analyses reveal patterns of brain functional interdependence that are overlooked with single metrics approaches, contributing to a more reliable and interpretable description of atypical functional connectivity in neurodegeneration.

Comparación del efecto de omeprazol como monoterapia y su combinación con bicarbonato de sodio en el tratamiento de la pirosis moderada a severa: ensayo clínico controlado, aleatorizado y doble ciego / Comparison of the effect of omeprazole monotherapy and its combination with sodium bicarbonate in the treatment of moderate to severe heartburn: a double-blind, randomized controlled clinical trial

Heartburn occurs in 75% of patients with digestive discomfort of any origin and is one of the main symptoms of gastroesophageal reflux disease. Treatment focuses on lifestyle modification and symptomatology management with various drugs; when heartburn is moderate to severe, a proton pump inhibitor is more suitable. Omeprazole (OMZ) combined with sodium bicarbonate (BC) has demonstrated significant and sustained suppression of acid secretion. The objective was to compare the effect of sequential OMZ/BC therapy compared to OMZ monotherapy for the improvement of heartburn in Mexican individuals. The study was a double-blind, randomized, controlled, multicenter clinical study including 277 subjects with moderate to severe heartburn. Patients received 7 days of OMZ/BC and 7 days of OMZ (OMZ/BC7) or 14 days of OMZ (OMZ14). The primary endpoint was defined as the change in the number of days a week that the patient has heartburn, it was evaluated at 14 days. Both treatments reduced time (days) with heartburn by less than 4 days (OMZ14 3.9 vs. 4.2 days OMZ/BC7), as well as duration, number of events and intensity of heartburn. The treatments improved the quality of life, and the control of the symptoms. The proportion of adverse events was lower with OMZ/BC. The non-inferiority of OMZ/BC7 with respect to OMZ14 was verified.

La pirosis se presenta en el 75% de los pacientes con molestias digestivas de cualquier origen y es uno de los principales síntomas de la enfermedad por reflujo gastroesofágico. El tratamiento se enfoca en la modificación del estilo de vida y el manejo de la sintomatología con diversos fármacos; cuando la pirosis es moderada a severa, un inhibidor de la bomba de protones es más adecuado. El omeprazol (OMZ) combinado con bicarbonato de sodio (BC) ha demostrado supresión significativa y sostenida de la secreción ácida. El objetivo fue comparar el efecto de la terapia secuencial de OMZ/BC en comparación con el tratamiento continuo de OMZ para la mejoría de la pirosis en individuos mexicanos. Estudio clínico multicéntrico, doble ciego, controlado, aleatorizado que incluyó 277 sujetos con pirosis moderada a severa. Los pacientes recibieron 7 días de OMZ/BC y 7 días de OMZ (OMZ/BC7) o 14 días de OMZ (OMZ14). La variable primaria fue definida como el cambio del número de días a la semana que el paciente presenta pirosis, se evaluó a los 14 días. Ambos tratamientos redujeron los días con pirosis en menos 4 días (OMZ14 3,9 vs. 4,2 días OMZ/BC7), así como la duración, el número de eventos e intensidad de la pirosis. Los tratamientos mejoraron los indicadores de calidad de vida, y el control del padecimiento. La proporción de eventos adversos fue menor con OMZ/BC. Se comprobó la no-inferioridad de OMZ/BC7 respecto OMZ14.

Prevalence of Mild Cognitive Impairment in Southern Regions of Colombia.

Background: Recent reports suggest that by 2050 there will be an increase of around 310% of cases affected by dementia in Latin American countries. A previous study in a Southern region reported one of the highest prevalences of dementia in Latin America. Objective: To investigate the prevalence of mild cognitive impairment associated with low education, rurality, and demographic characteristics. Methods: A cross-sectional study recruited a community-dwelling sample of 823 adults from rural and urban areas of two Southern provinces of Colombia from 2020-2022. Participants were assessed with a neuropsychological protocol validated in Colombia. To obtain general and region-specific prevalence rates, age, sex, schooling, and socioeconomic level were considered and controlled for. Results: Most of the participants reported low education and socioeconomic level, the participation of women was higher. It was determined that the prevalence of mild cognitive impairment (MCI) was 53.6%, with 56.6% in the province of Caquetá followed by 51.9% in the province of Huila. The amnestic MCI represented 42.6%, the amnestic multi-domain was 39%, the non-amnestic 16.55%, and the non-amnestic multi-domain 1.81%. Our participants reported comorbidities such as diabetes and hypertension. We also observed a relationship between exposure to pesticides and MCI. Conclusions: We observed one of the highest prevalences of MCI in Latin America reported to date. Variables such as age, gender, and education proved risk factors for MCI in the explored regions. Our findings are very much in line with recent studies that highlight the influence of non-canonical risk factors of dementia in underrepresented countries from Latin America.

Standardization and diagnostic utility of the Frontal Assessment Battery for healthy people and patients with dementia in the Chilean population.

The Frontal Assessment Battery (FAB) is a screening test that measures executive functions. Although this instrument has been validated in several countries, its diagnostic utility in a Chilean population has not been studied yet. Objectives: This study aimed to (1) adapt FAB in a Chilean population; (2) study the psychometric properties of the FAB in a Chilean population; (3) assess the sociodemographic influence in the performance of the FAB in a sample of healthy controls (HC); and (4) develop normative data for this healthy group. Methods: A HC (n=344) and a group of patients with dementia (n=156) were assessed with the Chilean version of FAB. Results: FAB showed good internal consistency (Cronbach's alpha=0.79) and acceptable validity based on the relationship with other variables. Factor analysis showed the unidimensionality of the instrument. Significant differences were found in the total FAB value between the HC and dementia groups. With the matched sample, the established cutoff point was 13.5, showing a sensitivity of 80.8% and a specificity of 90.4%. Regression analysis showed that education and age significantly predicted FAB performance in the healthy group. Finally, normative data are provided. Conclusions: This study shows that FAB is a useful tool to discriminate between healthy people and people with dementia. However, further studies are needed to explore the capacity of the instrument to characterize the dysexecutive syndrome in people with dementia in the Chilean population.

A Bateria de Avaliação Frontal (FAB) é um teste de rastreio que mede as funções executivas. Embora esse instrumento tenha sido validado em vários países, sua utilidade diagnóstica em uma população chilena ainda não foi estudada. Objetivos: (1) Adaptar a FAB para uma população chilena; (2) estudar as propriedades psicométricas da FAB em uma população chilena; (3) avaliar a influência sociodemográfica no desempenho da FAB em uma amostra de controles saudáveis; e (4) desenvolver dados normativos para este último grupo. Métodos: Um grupo controle saudável (n=344) e um grupo de pacientes com demência (n=156) foram avaliados com a versão chilena da FAB. Resultados: A FAB apresentou boa consistência interna (alfa de Cronbach=0,79) e validade aceitável com base na relação com outras variáveis. A análise fatorial mostrou a unidimensionalidade do instrumento. Diferenças significativas foram encontradas no valor total da FAB entre os grupos controle saudável e demência. Com a amostra pareada, o ponto de corte estabelecido foi de 13,5, que apresentou sensibilidade de 80,8% e especificidade de 90,4%. A análise de regressão mostrou que a escolaridade e a idade predisseram significativamente o desempenho da FAB no grupo saudável. Finalmente, os dados normativos são fornecidos. Conclusões: O presente estudo mostrou que a FAB é uma ferramenta útil para discriminar entre pessoas saudáveis e aquelas com demência. No entanto, mais estudos são necessários para explorar a capacidade do instrumento para caracterizar a síndrome disexecutiva em pessoas com demência na população chilena.

Dementia ConnEEGtome: Towards multicentric harmonization of EEG connectivity in neurodegeneration.

The proposal to use brain connectivity as a biomarker for dementia phenotyping can be potentiated by conducting large-scale multicentric studies using high-density electroencephalography (hd- EEG). Nevertheless, several barriers preclude the development of a systematic "ConnEEGtome" in dementia research. Here we review critical sources of variability in EEG connectivity studies, and provide general guidelines for multicentric protocol harmonization. We describe how results can be impacted by the choice for data acquisition, and signal processing workflows. The implementation of a particular processing pipeline is conditional upon assumptions made by researchers about the nature of EEG. Due to these assumptions, EEG connectivity metrics are typically applicable to restricted scenarios, e.g., to a particular neurocognitive disorder. "Ground truths" for the choice of processing workflow and connectivity analysis are impractical. Consequently, efforts should be directed to harmonizing experimental procedures, data acquisition, and the first steps of the preprocessing pipeline. Conducting multiple analyses of the same data and a proper integration of the results need to be considered in additional processing steps. Furthermore, instead of using a single connectivity measure, using a composite metric combining different connectivity measures brings a powerful strategy to scale up the replicability of multicentric EEG connectivity studies. These composite metrics can boost the predictive strength of diagnostic tools for dementia. Moreover, the implementation of multi-feature machine learning classification systems that include EEG-based connectivity analyses may help to exploit the potential of multicentric studies combining clinical-cognitive, molecular, genetics, and neuroimaging data towards a multi-dimensional characterization of the dementia.

Systematic Review: Genetic, Neuroimaging, and Fluids Biomarkers for Frontotemporal Dementia Across Latin America Countries.

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.

Attentional bias during emotional processing: Behavioral and electrophysiological evidence from an Emotional Flanker Task.

Threatening stimuli seem to capture attention more swiftly than neutral stimuli. This attention bias has been observed under different experimental conditions and with different types of stimuli. It remains unclear whether this adaptive behaviour reflects the function of automatic or controlled attention mechanisms. Additionally, the spatiotemporal dynamics of its neural correlates are largely unknown. The present study investigates these issues using an Emotional Flanker Task synchronized with EEG recordings. A group of 32 healthy participants saw response-relevant images (emotional scenes from IAPS or line drawings of objects) flanked by response-irrelevant distracters (i.e., emotional scenes flanked by line drawings or vice versa). We assessed behavioural and ERP responses drawn from four task conditions (Threat-Central, Neutral-Central, Threat-Peripheral, and Neutral-Peripheral) and subjected these responses to repeated-measures ANOVA models. When presented as response-relevant targets, threatening images attracted faster and more accurate responses. They did not affect response accuracy to targets when presented as response-irrelevant flankers. However, response times were significantly slower when threatening images flanked objects than when neutral images were shown as flankers. This result replicated the well-known Emotional Flanker Effect. Behavioural responses to response-relevant threatening targets were accompanied by significant modulations of ERP activity across all time-windows and regions of interest and displayed some meaningful correlations. The Emotional Flanker Effect was accompanied by a modulation over parietal and central-parietal regions within a time-window between 550-690ms. Such a modulation suggests that the attentional disruption to targets caused by response-irrelevant threatening flankers appears to reflect less neural resources available, which are seemingly drawn away by distracting threatening flankers. The observed spatiotemporal dynamics seem to concur with understanding of the important adaptive role attributed to threat-related attention bias.

Dementia in Latin America: Paving the way toward a regional action plan.

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.