Andrea María Slachevsky Conchol

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Slachevsky Chonchol, Andrea

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Slachevsky Chonchol

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Andrea

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Andrea María Slachevsky Conchol

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The impacts of social determinants of health and cardiometabolic factors on cognitive and functional aging in Colombian underserved populations
(2023) Santamaria, Hernando; Moguilner, Sebastian; Rodriguez, Odir; Botero, Felipe; Pina, Stefanie; O’Donovan, Gary; Albala, Cecilia; Matallana, Diana; Schulte, Michael; Slachevsky Chonchol, Andrea; Yokoyama, Jennifer; Possin, Katherine; Ndhlovu, Lishomwa; Al‑Rousan, Tala; Corley, Michael; Kosik, Kenneth; Muniz, Graciela; Miranda, J. Jaime; Ibanez, Agustin
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.
The first genome-wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease
(2024) Dalmasso, Maria; De Rojas, Itziar; Olivar, Natividad; Muchnik, Carolina; Angel, Bárbara; Gloger, Sergio; Sanchez, Mariana; Chacón, María; Aránguiz, Rafael; Orellana, Paulina; Cuesta, Carolina; Galeano, Pablo; Campanelli, Lorenzo; Novack, Gisela; Martinez, Luis; Medel, Nancy; Lisso, Julieta; Sevillano, Zulma; Irureta, Nicolás; Castaño, Eduardo; Montrreal, Laura; Thoenes, Michaela; Hanses, Claudia; Heilmann-Heimbach, Stefanie; Kairiyama, Claudia; Mintz, Inés; Villella, Ivana; Rueda, Fabiana; Romero, Amanda; Wukitsevits, Nancy; Quiroga, Ivana; Gona, Cristian; Lamber, Jean-Charles; Solis, Patricia; Politis, Daniel; Mangone, Carlos; Gonzalez, Christian; Boada, Mercè; Tàrraga, Lluís; Slachevsky Chonchol, Andrea
Introduction: Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. Methods: We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta-analysis and tested their genetic risk score (GRS) performance in this admixed population. Results: We detected apolipoprotein E ε4 as the single genome-wide significant signal (odds ratio = 2.93 [2.37-3.63], P = 2.6 × 10-23 ). The meta-analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD-GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose. Discussion: We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations. Highlights: This is the first genome-wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile. Trans-ethnic meta-analysis reveals four new loci involving lysosomal function in AD. This is the first independent replication for TREM2L, IGH-gene-cluster, and ADAM17 loci. A genetic risk score (GRS) developed in Europeans performed well in this population. The higher the Native American ancestry the lower the GRS values
The BrainLat project, a multimodal neuroimaging dataset of neurodegeneration from underrepresented backgrounds
(2023) Prado, Pavel; Medel, Vicente; Gonzalez, Raul; Sainz, Agustín; Vidal , Victor; Santamaría, Hernando; Moguilner, Sebastian; Mejia, Jhony; Slachevsky Chonchol, Andrea; Behrens, Maria; Aguillon, David; Lopera, Francisco; Parra, Mario; Matallana,Diana; Maito, Marcelo; Garcia, Adolfo; Custodio, Nilton; Ávila, Alberto; Piña, Stefanie; Birba, Agustina; Fittipaldi, Sol; Legaz, Agustina; Ibañez, Agustín
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.
Classification of Alzheimer’s disease and frontotemporal dementia using routine clinical and cognitive measures across multicentric underrepresented samples: a cross sectional observational study
(2023) Maito, Marcelo Adrián; Santamaría-García, Hernando; Moguilner, Sebastián; Possin, Katherine L.; Godoy, María E.; Avila-Funes, José Alberto; Behrens, Maria Isabel; Brusco, Ignacio L. Maira Okada de Oliveira,b,r,s,ae Stefanie D. Pina-Escuder; Bruno, Martín A.; Cardona, Juan F.; Custodio, Nilton; García, Adolfo M.; Javandel, Shireen; Lopera, Francisco; Matallana, Diana L.; Miller, Bruce; Okada de Oliveira, Maira; Pina Escudero, Stefanie; Slachevsky Chonchol, Andrea; Ana L Sosa Ortiz; Takada, Leonel T.; Tagliazuchi, Enzo; Valcour, Victor; Yokoyama, Jennifer S.; Ibañez, Agustín
Background Global 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. Methods This 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). Findings A 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. Interpretation Results 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.
Biomarkers for dementia in Latin American countries: Gaps andopportunities
(2023) Parra, Mario A.; Orellana, Paulina; León, Tomas; Victoria, Cabello G.; Henriquez, Fernando; Gomez, Rodrigo; Avalos, Constanza; Damian, Andres; Slachevsky Chonchol, Andrea; Ibañez, Agustin; Zetterberg, Henrik; Tijms, Betty M.; Yokoyama, Jennifer S.; Piña-Escudero, Stefanie D.; Cochran, Nicholas; Matallana, Diana L.; Acosta, Daisy; Allegri, Ricardo; Arias-Suáres, Bianca P.; Barra, Bernardo; Behrens, María Isabel; Brucki, Sonia M.D.; Busatto, Geraldo; Caramelli, Paulo; Castro-Suarez, Sheila; Contreras, Valeria; Custodio, Nilton; Dansilio, Sergio; De la Cruz-Puebla, Myriam; Cruz de Souza, Leonado; Díaz, Monica M.; Duque, Lissette; Farias, Gonzalo A.; Ferreira, Sergio T.; Magrath Guimet, Nahuel; Kmaid, Ana; Lira, David; Lopera, Francisco; Mar Meza, Beatriz; Miotto, Eliane C.
Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC)countries remains a serious barrier. Here, we reported a survey to explore the ongo-ing work, needs, interests, potential barriers, and opportunities for future studiesrelated to biomarkers. The results show that neuroimaging is the most used biomarker(73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cere-brospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears toundermine the implementation of biomarkers in clinical or research settings, followedby insufficient infrastructure and training. The survey revealed that despite the abovebarriers, 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 allowedus to propose an action plan that addresses the recommendations for a biomarkerframework recently proposed by regional experts.
Standardization and diagnostic utility of the Frontal Assessment Battery for healthy people and patients with dementia in the Chilean population
(2022) Grandi, Fabrissio; Martínez, David; Parra, Mario; Olavarria, Loreto; Huepe, David; Alegría, Patricia; Aliaga, Álvaro; Lillo, Patricia; Delgado, Carolina; Tenorio, Marcela; Rosas, Ricardo; López, Oscar; Becker, James; Slachevsky Chonchol, Andrea
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.
Multimodal Neurocognitive Markers of Naturalistic Discourse Typify Diverse Neurodegenerative Diseases
(2022) Birba, Agustina; Fittipaldi, Sol; Cediel Escobar, Judith C.; Gonzalez Campo, Cecilia; Legaz, Agustina; Galiani, Agostina; Díaz Rivera, Mariano N.; Martorell Caro, Miquel; Alifano, Florencia; Piña-Escudero, Stefanie D.; Cardona, Juan Felipe; Neely, Alejandra; Forno, Gonzalo; Carpinella , Mariela; Slachevsky Chonchol, Andrea; Serrano, Cecilia; Sedeño, Lucas; Ibáñez, Agustín; García, Adolfo M.
Neurodegeneration has multiscalar impacts, including behavioral, neuroanatomical, and neurofunctional disruptions. Can disease-differential alterations be captured across such dimensions using naturalistic stimuli? To address this question, we assessed comprehension of four naturalistic stories, highlighting action, nonaction, social, and nonsocial events, in Parkinson's disease (PD) and behavioral variant frontotemporal dementia (bvFTD) relative to Alzheimer's disease patients and healthy controls. Text-specific correlates were evaluated via voxel-based morphometry, spatial (fMRI), and temporal (hd-EEG) functional connectivity. PD patients presented action-text deficits related to the volume of action-observation regions, connectivity across motor-related and multimodal-semantic hubs, and frontal hd-EEG hypoconnectivity. BvFTD patients exhibited social-text deficits, associated with atrophy and spatial connectivity patterns along social-network hubs, alongside right frontotemporal hd-EEG hypoconnectivity. Alzheimer's disease patients showed impairments in all stories, widespread atrophy and spatial connectivity patterns, and heightened occipitotemporal hd-EEG connectivity. Our framework revealed disease-specific signatures across behavioral, neuroanatomical, and neurofunctional dimensions, highlighting the sensitivity and specificity of a single naturalistic task. This investigation opens a translational agenda combining ecological approaches and multimodal cognitive neuroscience for the study of neurodegeneration.
Allostatic-Interoceptive Overload in Frontotemporal Dementia
(2022) Birba, Agustina; Santamaría-García, Hernando; Prado, Pavel; Cruzat, Josefina; Sainz Ballesteros , Agustín; Legaz , Agustina; Fittipaldi, Sol; Duran-Aniotz , Claudia; Slachevsky Chonchol, Andrea; Santibañez , Rodrigo; Sigman , Mariano; M. García , Adolfo; Whelan , Robert; Moguilner , Sebastián; Ibáñez , Agustín
Background : The predictive coding theory of allostatic-interoceptive load states that brain networks mediating autonomic regulation and interoceptive-exteroceptive balance regulate the internal milieu to anticipate future needs and environmental demands. These functions seem to be distinctly compromised in behavioral variant frontotemporal dementia (bvFTD), including alterations of the allostatic-interoceptive network (AIN). Here, we hypothesize that bvFTD is typified by an allostatic-interoceptive overload. Methods : We assessed resting-state heartbeat evoked potential (rsHEP) modulation as well as its behavioral and multimodal neuroimaging correlates in patients with bvFTD relative to healthy control subjects and patients with Alzheimer’s disease (N = 94). We measured 1) resting-state electroencephalography (to assess the rsHEP, prompted by visceral inputs and modulated by internal body sensing), 2) associations between rsHEP and its neural generators (source location), 3) cognitive disturbances (cognitive state, executive functions, facial emotion recognition), 4) brain atrophy, and 5) resting-state functional magnetic resonance imaging functional connectivity (AIN vs. control networks). Results : Relative to healthy control subjects and patients with Alzheimer’s disease, patients with bvFTD presented more negative rsHEP amplitudes with sources in critical hubs of the AIN (insula, amygdala, somatosensory cortex, hippocampus, anterior cingulate cortex). This exacerbated rsHEP modulation selectively predicted the patients’ cognitive profile (including cognitive decline, executive dysfunction, and emotional impairments). In addition, increased rsHEP modulation in bvFTD was associated with decreased brain volume and connectivity of the AIN. Machine learning results confirmed AIN specificity in predicting the bvFTD group. Conclusions : Altogether, these results suggest that bvFTD may be characterized by an allostatic-interoceptive overload manifested in ongoing electrophysiological markers, brain atrophy, functional networks, and cognition.
Normalization of Rowland Universal Dementia Assessment Scale (RUDAS) in Chilean older people
(2023) Sepúlveda-Ibarra, Consuelo; Henríquez Chaparro, Fernando; Marcittum Anthony; Soto, Guillermo; Slachevsky Chonchol, Andrea
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.
Multidimensional inhibitory signatures of sentential negation in behavioral variant frontotemporal dementia
(2023) Díaz-Rivera, Mariano N.; Birba, Agustina; Fittipaldi, Sol; Mola, Débora; Morera, Yurena; Vega, Manuel de; Moguilner, Sebastian; Lillo, Patricia; Slachevsky Chonchol, Andrea; González Campo, Cecilia; Ibáñez, Agustín; García, Adolfo M.
Background Processing of linguistic negation has been associated to inhibitory brain mechanisms. However, no study has tapped this link via multimodal measures in patients with core inhibitory alterations, a critical approach to reveal direct neural correlates and potential disease markers. Methods Here we examined oscillatory, neuroanatomical, and functional connectivity signatures of a recently reported Go/No-go negation task in healthy controls and behavioral variant frontotemporal dementia (bvFTD) patients, typified by primary and generalized inhibitory disruptions. To test for specificity, we also recruited persons with Alzheimer's disease (AD), a disease involving frequent but nonprimary inhibitory deficits. Results In controls, negative sentences in the No-go condition distinctly involved frontocentral delta (2–3 Hz) suppression, a canonical inhibitory marker. In bvFTD patients, this modulation was selectively abolished and significantly correlated with the volume and functional connectivity of regions supporting inhibition (e.g. precentral gyrus, caudate nucleus, and cerebellum). Such canonical delta suppression was preserved in the AD group and associated with widespread anatomo-functional patterns across non-inhibitory regions. Discussion These findings suggest that negation hinges on the integrity and interaction of spatiotemporal inhibitory mechanisms. Moreover, our results reveal potential neurocognitive markers of bvFTD, opening a new agenda at the crossing of cognitive neuroscience and behavioral neurology.