Person: Slachevsky Conchol, Andrea
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Slachevsky Conchol
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Andrea
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Andrea María Slachevsky Conchol
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Publication 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 Conchol, Andrea; Yokoyama, Jennifer; Possin, Katherine; Ndhlovu, Lishomwa; Al‑Rousan, Tala; Corley, Michael; Kosik, Kenneth; Muniz, Graciela; Miranda, J. Jaime; Ibanez, AgustinGlobal 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.Publication 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 Conchol, AndreaIntroduction: 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 valuesPublication 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 Conchol, 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, AgustínThe 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.Publication 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 Conchol, AndreaThe 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.Publication Validation of Picture Free and Cued Selective Reminding Test for Illiteracy in Lima, Perú(2022) Montesinos, Rosa; Parodi, José; Díaz, Mónica; Herrera, Eder; Valeriano, Elizabeth; Soto, Ambar; Delgado, Carolina; Slachevsky Conchol, Andrea; Custodio, NiltonDementia in Latin America is a crucial public health problem. Identifying brief cognitive screening (BCS) tools for the primary care setting is crucial, particularly for illiterate individuals. We evaluated tool performance characteristics and validated the free and total recall sections of the Free and Cued Selective Reminding Test-Picture version (FCSRT-Picture) to discriminate between 63 patients with early Alzheimer's disease dementia (ADD), 60 amnestic mild cognitive impairment (aMCI) and 64 cognitively healthy Peruvian individuals with illiteracy from an urban area. Clinical, functional, and cognitive assessments were performed. FCSRT-Picture performance was assessed using receiver operating characteristic curve analyses. The mean ± standard deviation scores were 7.7 ± 1.0 in ADD, 11.8 ± 1.6 in aMCI, and 29.5 ± 1.8 in controls. The FCSRT-Picture had better performance characteristics for distinguishing controls from aMCI compared with several other BCS tools, but similar characteristics between controls and early ADD. The FCSRT-Picture is a reliable BCS tool for illiteracy in Perú.Publication Multimodal mechanisms of human sociallyreinforced learning across neurodegenerative diseases(2022) Legaz, Agustina; Abrevaya, Sofía; Dottori, Martín; González, Cecilia; Birba, Agustina; Martorell, Miguel; Aguirre, Julieta; Slachevsky Conchol, Andrea; Aranguiz, Rafael; Serrano, Cecilia; Gillan, Claire; Leroi, Iracema; García, Adolfo; Fittipaldi, Sol; Ibañez, AgustínSocial feedback can selectively enhance learning in diverse domains. Relevant neurocognitive mechanisms have been studied mainly in healthy persons, yielding correlational findings. Neurodegenerative lesion models, coupled with multimodal brain measures, can complement standard approaches by revealing direct multidimensional correlates of the phenomenon. To this end, we assessed socially reinforced and non-socially reinforced learning in 40 healthy participants as well as persons with behavioural variant frontotemporal dementia (n = 21), Parkinson's disease (n = 31) and Alzheimer's disease (n = 20). These conditions are typified by predominant deficits in social cognition, feedback-based learning and associative learning, respectively, although all three domains may be partly compromised in the other conditions. We combined a validated behavioural task with ongoing EEG signatures of implicit learning (medial frontal negativity) and offline MRI measures (voxel-based morphometry). In healthy participants, learning was facilitated by social feedback relative to non-social feedback. In comparison with controls, this effect was specifically impaired in behavioural variant frontotemporal dementia and Parkinson's disease, while unspecific learning deficits (across social and non-social conditions) were observed in Alzheimer's disease. EEG results showed increased medial frontal negativity in healthy controls during social feedback and learning. Such a modulation was selectively disrupted in behavioural variant frontotemporal dementia. Neuroanatomical results revealed extended temporo-parietal and fronto-limbic correlates of socially reinforced learning, with specific temporo-parietal associations in behavioural variant frontotemporal dementia and predominantly fronto-limbic regions in Alzheimer's disease. In contrast, non-socially reinforced learning was consistently linked to medial temporal/hippocampal regions. No associations with cortical volume were found in Parkinson's disease. Results are consistent with core social deficits in behavioural variant frontotemporal dementia, subtle disruptions in ongoing feedback-mechanisms and social processes in Parkinson's disease and generalized learning alterations in Alzheimer's disease. This multimodal approach highlights the impact of different neurodegenerative profiles on learning and social feedback. Our findings inform a promising theoretical and clinical agenda in the fields of social learning, socially reinforced learning and neurodegeneration.Publication Multi-feature computational framework for combined signatures of dementia in underrepresented settings(2022) Moguilner, Sebastián; Birba, Agustina; Fittipaldi, Sol; Gonzalez, Cecilia; Tagliazucchi, Enzo; Reyes, Pablo; Matallana, Diana; Parra, Mario; Slachevsky Conchol, Andrea; Farías, Gonzalo; Cruzat, Josefina; García, Adolfo; Eyre, Harris; La Joie, Renaud; Rabinovici, Gil; Whelan, Robert; Ibáñez, AgustínObjective.The differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's 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