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1. Multiplex Nodal Modularity: A novel network metric for the regional analysis of amnestic mild cognitive impairment during a working memory binding task

Author

Campbell-Cousins, Avalon, Guazzo, Federica, Bastin, Mark, Parra, Mario A., and Escudero, Javier

Subjects
Quantitative Biology - Neurons and Cognition, Computer Science - Social and Information Networks, Physics - Biological Physics
Abstract

Modularity is a well-established concept for assessing community structures in various single and multi-layer networks, including those in biological and social domains. Biological networks, such as the brain, are known to exhibit group structure at a variety of scales -- local, meso, and global scale. Modularity, while useful in describing mesoscale brain organization, is limited as a metric to a global scale describing the overall strength of community structure. This approach, while valuable, overlooks important localized variations in community structure at the node level. To address this limitation, we extended modularity to individual nodes. This novel measure of nodal modularity ($nQ$) captures both meso and local scale changes in modularity. We hypothesized that $nQ$ illuminates granular changes in the brain due to diseases such as Alzheimer's disease (AD), which are known to disrupt the brain's modular structure. We explored $nQ$ in multiplex networks of a visual short-term memory binding task in fMRI and DTI data in the early stages of AD. Observed changes in $nQ$ in fMRI and DTI networks aligned with known trajectories of AD and were linked to common biomarkers of the disease, including amyloid-$\beta$ and tau. Additionally, $nQ$ clearly differentiated MCI from MCI converters showing indications that $nQ$ may be a useful diagnostic tool for characterizing disease stages. Our findings demonstrate the utility of $nQ$ as a measure of localized group structure, providing novel insights into temporal and disease related variability at the node level. Given the widespread application of modularity as a global measure, $nQ$ represents a significant advancement, providing a granular measure of network organization applicable to a wide range of disciplines., Comment: 37 pages, 11 figures, this is to be submitted to PLOS ONE for publication

Published
2025

2. Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations

Author

Moguilner, Sebastian, Baez, Sandra, Hernandez, Hernan, Migeot, Joaquín, Legaz, Agustina, Gonzalez-Gomez, Raul, Farina, Francesca R, Prado, Pavel, Cuadros, Jhosmary, Tagliazucchi, Enzo, Altschuler, Florencia, Maito, Marcelo Adrián, Godoy, María E, Cruzat, Josephine, Valdes-Sosa, Pedro A, Lopera, Francisco, Ochoa-Gómez, John Fredy, Hernandez, Alfredis Gonzalez, Bonilla-Santos, Jasmin, Gonzalez-Montealegre, Rodrigo A, Anghinah, Renato, d’Almeida Manfrinati, Luís E, Fittipaldi, Sol, Medel, Vicente, Olivares, Daniela, Yener, Görsev G, Escudero, Javier, Babiloni, Claudio, Whelan, Robert, Güntekin, Bahar, Yırıkoğulları, Harun, Santamaria-Garcia, Hernando, Lucas, Alberto Fernández, Huepe, David, Di Caterina, Gaetano, Soto-Añari, Marcio, Birba, Agustina, Sainz-Ballesteros, Agustin, Coronel-Oliveros, Carlos, Yigezu, Amanuel, Herrera, Eduar, Abasolo, Daniel, Kilborn, Kerry, Rubido, Nicolás, Clark, Ruaridh A, Herzog, Ruben, Yerlikaya, Deniz, Hu, Kun, Parra, Mario A, Reyes, Pablo, García, Adolfo M, Matallana, Diana L, Avila-Funes, José Alberto, Slachevsky, Andrea, Behrens, María I, Custodio, Nilton, Cardona, Juan F, Barttfeld, Pablo, Brusco, Ignacio L, Bruno, Martín A, Sosa Ortiz, Ana L, Pina-Escudero, Stefanie D, Takada, Leonel T, Resende, Elisa, Possin, Katherine L, de Oliveira, Maira Okada, Lopez-Valdes, Alejandro, Lawlor, Brian, Robertson, Ian H, Kosik, Kenneth S, Duran-Aniotz, Claudia, Valcour, Victor, Yokoyama, Jennifer S, Miller, Bruce, and Ibanez, Agustin

Subjects
Health Services and Systems, Health Sciences, Neurosciences, Neurodegenerative, Minority Health, Alzheimer's Disease Related Dementias (ADRD), Clinical Research, Alzheimer's Disease, Acquired Cognitive Impairment, Brain Disorders, Bioengineering, Vascular Cognitive Impairment/Dementia, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Behavioral and Social Science, Dementia, Cerebrovascular, Basic Behavioral and Social Science, Health Disparities, Neurological, Humans, Male, Brain, Female, Aged, Magnetic Resonance Imaging, Electroencephalography, Middle Aged, Alzheimer Disease, Cognitive Dysfunction, Aged, 80 and over, Health Status Disparities, Socioeconomic Factors, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

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.

Published
2024

3. Graph Permutation Entropy: Extensions to the Continuous Case, A step towards Ordinal Deep Learning, and More

Author

Roy, Om, Campbell-Cousins, Avalon, Carrasco, John Stewart Fabila, Parra, Mario A, and Escudero, Javier

Subjects
Nonlinear Sciences - Chaotic Dynamics
Abstract

Nonlinear dynamics play an important role in the analysis of signals. A popular, readily interpretable nonlinear measure is Permutation Entropy. It has recently been extended for the analysis of graph signals, thus providing a framework for non-linear analysis of data sampled on irregular domains. Here, we introduce a continuous version of Permutation Entropy, extend it to the graph domain, and develop a ordinal activation function akin to the one of neural networks. This is a step towards Ordinal Deep Learning, a potentially effective and very recently posited concept. We also formally extend ordinal contrasts to the graph domain. Continuous versions of ordinal contrasts of length 3 are also introduced and their advantage is shown in experiments. We also integrate specific contrasts for the analysis of images and show that it generalizes well to the graph domain allowing a representation of images, represented as graph signals, in a plane similar to the entropy-complexity one. Applications to synthetic data, including fractal patterns and popular non-linear maps, and real-life MRI data show the validity of these novel extensions and potential benefits over the state of the art. By extending very recent concepts related to permutation entropy to the graph domain, we expect to accelerate the development of more graph-based entropy methods to enable nonlinear analysis of a broader kind of data and establishing relationships with emerging ideas in data science.

Published
2024

4. FAST functional connectivity implicates P300 connectivity in working memory deficits in Alzheimer's disease

Author

Roy, Om, Moshfeghi, Yashar, Ibanez, Agustin, Lopera, Francisco, Parra, Mario A, and Smith, Keith M

Subjects
Quantitative Biology - Neurons and Cognition, Electrical Engineering and Systems Science - Signal Processing
Abstract

Measuring transient functional connectivity is an important challenge in Electroencephalogram (EEG) research. Here, the rich potential for insightful, discriminative information of brain activity offered by high temporal resolution is confounded by the inherent noise of the medium and the spurious nature of correlations computed over short temporal windows. We propose a novel methodology to overcome these problems called Filter Average Short-Term (FAST) functional connectivity. First, long-term, stable, functional connectivity is averaged across an entire study cohort for a given pair of Visual Short Term Memory (VSTM) tasks. The resulting average connectivity matrix, containing information on the strongest general connections for the tasks, is used as a filter to analyse the transient high temporal resolution functional connectivity of individual subjects. In simulations, we show that this method accurately discriminates differences in noisy Event-Related Potentials (ERPs) between two conditions where standard connectivity and other comparable methods fail. We then apply this to analyse activity related to visual short-term memory binding deficits in two cohorts of familial and sporadic Alzheimer's disease. Reproducible significant differences were found in the binding task with no significant difference in the shape task in the P300 ERP range. This allows new sensitive measurements of transient functional connectivity, which can be implemented to obtain results of clinical significance., Comment: Published in Network Neuroscience (2024) by MIT Press

Published
2024
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5. Author Correction: The BrainLat project, a multimodal neuroimaging dataset of neurodegeneration from underrepresented backgrounds

Author

Prado, Pavel, Medel, Vicente, Gonzalez-Gomez, Raul, Sainz-Ballesteros, Agustín, Vidal, Victor, Santamaría-García, Hernando, Moguilner, Sebastian, Mejia, Jhony, Slachevsky, Andrea, Behrens, Maria Isabel, Aguillon, David, Lopera, Francisco, Parra, Mario A., Matallana, Diana, Maito, Marcelo Adrián, Garcia, Adolfo M., Custodio, Nilton, Funes, Alberto Ávila, Piña-Escudero, Stefanie, Birba, Agustina, Fittipaldi, Sol, Legaz, Agustina, and Ibañez, Agustín

Published
2024
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6. Author Correction: Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations

Author

Moguilner, Sebastian, Baez, Sandra, Hernandez, Hernan, Migeot, Joaquín, Legaz, Agustina, Gonzalez-Gomez, Raul, Farina, Francesca R., Prado, Pavel, Cuadros, Jhosmary, Tagliazucchi, Enzo, Altschuler, Florencia, Maito, Marcelo Adrián, Godoy, María E., Cruzat, Josephine, Valdes-Sosa, Pedro A., Lopera, Francisco, Ochoa-Gómez, John Fredy, Hernandez, Alfredis Gonzalez, Bonilla-Santos, Jasmin, Gonzalez-Montealegre, Rodrigo A., Anghinah, Renato, d’Almeida Manfrinati, Luís E., Fittipaldi, Sol, Medel, Vicente, Olivares, Daniela, Yener, Görsev G., Escudero, Javier, Babiloni, Claudio, Whelan, Robert, Güntekin, Bahar, Yırıkoğulları, Harun, Santamaria-Garcia, Hernando, Lucas, Alberto Fernández, Huepe, David, Di Caterina, Gaetano, Soto-Añari, Marcio, Birba, Agustina, Sainz-Ballesteros, Agustin, Coronel-Oliveros, Carlos, Yigezu, Amanuel, Herrera, Eduar, Abasolo, Daniel, Kilborn, Kerry, Rubido, Nicolás, Clark, Ruaridh A., Herzog, Ruben, Yerlikaya, Deniz, Hu, Kun, Parra, Mario A., Reyes, Pablo, García, Adolfo M., Matallana, Diana L., Avila-Funes, José Alberto, Slachevsky, Andrea, Behrens, María I., Custodio, Nilton, Cardona, Juan F., Barttfeld, Pablo, Brusco, Ignacio L., Bruno, Martín A., Sosa Ortiz, Ana L., Pina-Escudero, Stefanie D., Takada, Leonel T., Resende, Elisa, Possin, Katherine L., de Oliveira, Maira Okada, Lopez-Valdes, Alejandro, Lawlor, Brian, Robertson, Ian H., Kosik, Kenneth S., Duran-Aniotz, Claudia, Valcour, Victor, Yokoyama, Jennifer S., Miller, Bruce, and Ibanez, Agustin

Published
2024
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8. Biomarkers for dementia in Latin American countries: Gaps and opportunities.

Author

Parra, Mario, Orellana, Paulina, Leon, Tomas, Victoria, Cabello, Henriquez, Fernando, Gomez, Rodrigo, Avalos, Constanza, Damian, Andres, Slachevsky, Andrea, Ibañez, Agustin, Zetterberg, Henrik, Tijms, Betty, Yokoyama, Jennifer, Piña-Escudero, Stefanie, Cochran, J, Matallana, Diana, Acosta, Daisy, Allegri, Ricardo, Arias-Suárez, Bianca, Barra, Bernardo, Behrens, Maria, Brucki, Sonia, Busatto, Geraldo, Caramelli, Paulo, Castro-Suarez, Sheila, Contreras, Valeria, Custodio, Nilton, Dansilio, Sergio, la Cruz-Puebla, Myriam, de Souza, Leonardo, Diaz, Monica, Duque, Lissette, Farías, Gonzalo, Ferreira, Sergio, Guimet, Nahuel, Kmaid, Ana, Lira, David, Lopera, Francisco, Meza, Beatriz, Miotto, Eliane, Nitrini, Ricardo, Nuñez, Alberto, ONeill, Santiago, Ochoa, John, Pintado-Caipa, Maritza, Resende, Elisa, Risacher, Shannon, Rojas, Luz, Sabaj, Valentina, Schilling, Lucas, Sellek, Allis, Sosa, Ana, Takada, Leonel, Teixeira, Antonio, Unaucho-Pilalumbo, Martha, and Duran-Aniotz, Claudia

Subjects
Humans, Latin America, Dementia
Abstract

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.

Published
2023

9. Multi-feature computational framework for combined signatures of dementia in underrepresented settings.

Author

Moguilner, Sebastian, Birba, Agustina, Fittipaldi, Sol, Gonzalez-Campo, Cecilia, Tagliazucchi, Enzo, Reyes, Pablo, Matallana, Diana, Parra, Mario, Slachevsky, Andrea, Farías, Gonzalo, Cruzat, Josefina, García, Adolfo, Eyre, Harris, La Joie, Renaud, Rabinovici, Gil, Whelan, Robert, and Ibáñez, Agustín

Subjects
feature selection, harmonization, machine learning, multimodal neuroimaging, neurodegeneration, Alzheimer Disease, Bayes Theorem, Biomarkers, Brain, Frontotemporal Dementia, Humans, Magnetic Resonance Imaging, Neuropsychological Tests
Abstract

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.

Published
2022

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

Author

Hernandez, Hernan, Baez, Sandra, Medel, Vicente, Moguilner, Sebastian, Cuadros, Jhosmary, Santamaria-Garcia, Hernando, Tagliazucchi, Enzo, Valdes-Sosa, Pedro A., Lopera, Francisco, OchoaGómez, John Fredy, González-Hernández, Alfredis, Bonilla-Santos, Jasmin, Gonzalez-Montealegre, Rodrigo A., Aktürk, Tuba, Yıldırım, Ebru, Anghinah, Renato, Legaz, Agustina, Fittipaldi, Sol, Yener, Görsev G., Escudero, Javier, Babiloni, Claudio, Lopez, Susanna, Whelan, Robert, Lucas, Alberto A Fernández, García, Adolfo M., Huepe, David, Caterina, Gaetano Di, Soto-Añari, Marcio, Birba, Agustina, Sainz-Ballesteros, Agustin, Coronel, Carlos, Herrera, Eduar, Abasolo, Daniel, Kilborn, Kerry, Rubido, Nicolás, Clark, Ruaridh, Herzog, Ruben, Yerlikaya, Deniz, Güntekin, Bahar, Parra, Mario A., Prado, Pavel, and Ibanez, Agustin

Published
2024
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11. The BrainLat project, a multimodal neuroimaging dataset of neurodegeneration from underrepresented backgrounds

Author

Prado, Pavel, Medel, Vicente, Gonzalez-Gomez, Raul, Sainz-Ballesteros, Agustín, Vidal, Victor, Santamaría-García, Hernando, Moguilner, Sebastian, Mejia, Jhony, Slachevsky, Andrea, Behrens, Maria Isabel, Aguillon, David, Lopera, Francisco, Parra, Mario A., Matallana, Diana, Maito, Marcelo Adrián, Garcia, Adolfo M., Custodio, Nilton, Funes, Alberto Ávila, Piña-Escudero, Stefanie, Birba, Agustina, Fittipaldi, Sol, Legaz, Agustina, and Ibañez, Agustín

Published
2023
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14. Dementia in Latin America: Paving the way toward a regional action plan.

Author

Parra, Mario Alfredo, Baez, Sandra, Sedeño, Lucas, Gonzalez Campo, Cecilia, Santamaría-García, Hernando, Aprahamian, Ivan, Bertolucci, Paulo Hf, Bustin, Julian, Camargos Bicalho, Maria Aparecida, Cano-Gutierrez, Carlos, Caramelli, Paulo, Chaves, Marcia LF, Cogram, Patricia, Beber, Bárbara Costa, Court, Felipe A, de Souza, Leonardo Cruz, Custodio, Nilton, Damian, Andres, de la Cruz, Myriam, Diehl Rodriguez, Roberta, Brucki, Sonia Maria Dozzi, Fajersztajn, Lais, Farías, Gonzalo A, De Felice, Fernanda G, Ferrari, Raffaele, de Oliveira, Fabricio Ferreira, Ferreira, Sergio T, Ferretti, Ceres, Figueredo Balthazar, Marcio Luiz, Ferreira Frota, Norberto Anizio, Fuentes, Patricio, García, Adolfo M, Garcia, Patricia J, de Gobbi Porto, Fábio Henrique, Duque Peñailillo, Lissette, Engler, Henry Willy, Maier, Irene, Mata, Ignacio F, Gonzalez-Billault, Christian, Lopez, Oscar L, Morelli, Laura, Nitrini, Ricardo, Quiroz, Yakeel T, Guerrero Barragan, Alejandra, Huepe, David, Pio, Fabricio Joao, Suemoto, Claudia Kimie, Kochhann, Renata, Kochen, Silvia, Kumfor, Fiona, Lanata, Serggio, Miller, Bruce, Mansur, Leticia Lessa, Hosogi, Mirna Lie, Lillo, Patricia, Llibre Guerra, Jorge, Lira, David, Lopera, Francisco, Comas, Adelina, Avila-Funes, José Alberto, Sosa, Ana Luisa, Ramos, Claudia, Resende, Elisa de Paula França, Snyder, Heather M, Tarnanas, Ioannis, Yokoyama, Jenifer, Llibre, Juan, Cardona, Juan Felipe, Possin, Kate, Kosik, Kenneth S, Montesinos, Rosa, Moguilner, Sebastian, Solis, Patricia Cristina Lourdes, Ferretti-Rebustini, Renata Eloah de Lucena, Ramirez, Jeronimo Martin, Matallana, Diana, Mbakile-Mahlanza, Lingani, Marques Ton, Alyne Mendonça, Tavares, Ronnielly Melo, Miotto, Eliane C, Muniz-Terrera, Graciela, Muñoz-Nevárez, Luis Arnoldo, Orozco, David, Okada de Oliveira, Maira, Piguet, Olivier, Pintado Caipa, Maritza, Piña Escudero, Stefanie Danielle, Schilling, Lucas Porcello, Rodrigues Palmeira, André Luiz, Yassuda, Mônica Sanches, Santacruz-Escudero, Jose Manuel, Serafim, Rodrigo Bernardo, Smid, Jerusa, Slachevsky, Andrea, Serrano, Cecilia, Soto-Añari, Marcio, Takada, Leonel Tadao, Grinberg, Lea Tenenholz, Teixeira, Antonio Lucio, and Barbosa, Maira Tonidandel

Subjects
Latin America, biomarkers, clinical trials, dementia, epidemiology, evidence-based recommendations, genetics, knowledge to action framework, networking and translational research, nonpharmacological interventions, Dementia, Clinical Research, Brain Disorders, Aging, Acquired Cognitive Impairment, Prevention, Neurological, Clinical Sciences, Neurosciences, Geriatrics
Abstract

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.

Published
2021

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

Author

Duran-Aniotz, Claudia, Orellana, Paulina, Rodriguez, Tomas Leon, Henriquez, Fernando, Cabello, Victoria, Aguirre-Pinto, María F, Escobedo, Tamara, Takada, Leonel T, Pina-Escudero, Stefanie D, Lopez, Oscar, Yokoyama, Jennifer S, Ibanez, Agustin, Parra, Mario A, and Slachevsky, Andrea

Subjects
Biological Psychology, Psychology, Rare Diseases, Brain Disorders, Frontotemporal Dementia (FTD), Acquired Cognitive Impairment, Behavioral and Social Science, Aging, Basic Behavioral and Social Science, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Research, Neurosciences, Dementia, Genetics, Neurodegenerative, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Neurological, Mental health, Good Health and Well Being, frontotemporal dementia, genetics, neuroimaging, fluid biomarkers, Latin America, Clinical Sciences, Clinical sciences, Biological psychology
Abstract

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.

Published
2021

17. The impact of SARS‐CoV‐2 in dementia across Latin America: A call for an urgent regional plan and coordinated response

Author

Ibanez, Agustin, Santamaria‐Garcia, Hernando, Barragan, Alejandra Guerrero, Kornhuber, Alexander, Ton, Alyne Mendonca Marques, Slachevsky, Andrea, Teixeira, Antonio Lucio, Meza, Beatriz Marcela Mar, Serrano, Cecilia M, Cano, Carlos, Gonzalez, Carolina Arias, Gonzalez‐Billault, Christian, Butler, Christopher, Bustin, Julian, Duran‐Aniotz, Claudia, Acosta, Daisy, Matallana, Diana L, Acosta‐Alvear, Diego, Trépel, Dominic, De Paula França Resende, Elisa, Oliveira, Fabricio Ferreira, Ibanez, Francisco, De Felice, Fernanda G, Navarrete, Gorka, Tarnanas, Ioannis, Meier, Irene B, Smid, Jerusa, Llibre‐Guerra, Jorge, Llibre‐Rodriguez, Juan J, Fajersztajn, Laís, Takada, Leonel Tadao, Duque, Lissette, de Oliveira, Maira Okada, Bicalho, Maria Aparecida Camargos, Behrens, María Isabel, Pintado‐Caipa, Maritza, Parra, Mario, Wilson, Maxwell Z, De La Cruz Puebla, Myriam, Custodio, Nilton, Santibanez, Rodrigo, Serafim, Rodrigo Bernardo, Tavares, Ronnielly Melo, Escudero, Stefanie Danielle Piña, Rodriguez, Tomas Leon, Dawson, Walter, Miller, Bruce L, and Kosik, Kenneth S

Subjects
Emerging Infectious Diseases, Brain Disorders, Prevention, Acquired Cognitive Impairment, Dementia, Neurological, Reduced Inequalities, coronavirus, dementia, health system, Latin American and Caribbean countries, SARS-CoV-2, SARS‐CoV‐2
Abstract

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.

Published
2020

18. Complex tensor factorisation with PARAFAC2 for the estimation of brain connectivity from the EEG

Author

Spyrou, Loukianos, Parra, Mario, and Escudero, Javier

Subjects
Computer Science - Computational Engineering, Finance, and Science, Quantitative Biology - Neurons and Cognition
Abstract

Objective: The coupling between neuronal populations and its magnitude have been shown to be informative for various clinical applications. One method to estimate brain connectivity is with electroencephalography (EEG) from which the cross-spectrum between different sensor locations is derived. We wish to test the efficacy of tensor factorisation in the estimation of brain connectivity. Methods: Complex tensor factorisation based on PARAFAC2 is used to decompose the EEG into scalp components described by the spatial, spectral, and complex trial profiles. An EEG model in the complex domain was derived that shows the suitability of PARAFAC2. A connectivity metric was also derived on the complex trial profiles of the extracted components. Results: Results on a benchmark EEG dataset confirmed that PARAFAC2 can estimate connectivity better than traditional tensor analysis such as PARAFAC within a range of signal-to-noise ratios. The analysis of EEG from patients with mild cognitive impairment or Alzheimer's disease showed that PARAFAC2 identifies loss of brain connectivity better than traditional approaches and agreeing with prior pathological knowledge. Conclusion: The complex PARAFAC2 algorithm is suitable for EEG connectivity estimation since it allows to extract meaningful coupled sources and provides better estimates than complex PARAFAC. Significance: A new paradigm that employs complex tensor factorisation has demonstrated to be successful in identifying brain connectivity and the location of couples sources for both a benchmark and a real-world EEG dataset. This can enable future applications and has the potential to solve some the issues that deteriorate the performance of traditional connectivity metrics.

Published
2017

19. Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need.

Author

Babulal, Ganesh M, Quiroz, Yakeel T, Albensi, Benedict C, Arenaza-Urquijo, Eider, Astell, Arlene J, Babiloni, Claudio, Bahar-Fuchs, Alex, Bell, Joanne, Bowman, Gene L, Brickman, Adam M, Chételat, Gaël, Ciro, Carrie, Cohen, Ann D, Dilworth-Anderson, Peggye, Dodge, Hiroko H, Dreux, Simone, Edland, Steven, Esbensen, Anna, Evered, Lisbeth, Ewers, Michael, Fargo, Keith N, Fortea, Juan, Gonzalez, Hector, Gustafson, Deborah R, Head, Elizabeth, Hendrix, James A, Hofer, Scott M, Johnson, Leigh A, Jutten, Roos, Kilborn, Kerry, Lanctôt, Krista L, Manly, Jennifer J, Martins, Ralph N, Mielke, Michelle M, Morris, Martha Clare, Murray, Melissa E, Oh, Esther S, Parra, Mario A, Rissman, Robert A, Roe, Catherine M, Santos, Octavio A, Scarmeas, Nikolaos, Schneider, Lon S, Schupf, Nicole, Sikkes, Sietske, Snyder, Heather M, Sohrabi, Hamid R, Stern, Yaakov, Strydom, Andre, Tang, Yi, Terrera, Graciela Muniz, Teunissen, Charlotte, Melo van Lent, Debora, Weinborn, Michael, Wesselman, Linda, Wilcock, Donna M, Zetterberg, Henrik, O'Bryant, Sid E, and International Society to Advance Alzheimer's Research and Treatment, Alzheimer's Association

Subjects
International Society to Advance Alzheimer's Research and Treatment, Alzheimer's Association, Humans, Alzheimer Disease, Biomedical Research, Aged, Continental Population Groups, Ethnic Groups, Healthcare Disparities, Biomarkers, Alzheimer's disease, Alzheimer's related dementias, Diversity, Ethnicity, Ethnoracial, Translational, Underserved, Geriatrics, Clinical Sciences, Neurosciences
Abstract

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.

Published
2019

22. Locating Temporal Functional Dynamics of Visual Short-Term Memory Binding using Graph Modular Dirichlet Energy

Author

Smith, Keith, Ricaud, Benjamin, Shahid, Nauman, Rhodes, Stephen, Starr, John M., Ibanez, Agustin, Parra, Mario A., Escudero, Javier, and Vandergheynst, Pierre

Subjects
Quantitative Biology - Neurons and Cognition
Abstract

Visual short-term memory binding tasks are a promising early marker for Alzheimer's disease (AD). To uncover functional deficits of AD in these tasks it is meaningful to first study unimpaired brain function. Electroencephalogram recordings were obtained from encoding and maintenance periods of tasks performed by healthy young volunteers. We probe the task's transient physiological underpinnings by contrasting shape only (Shape) and shape-colour binding (Bind) conditions, displayed in the left and right sides of the screen, separately. Particularly, we introduce and implement a novel technique named Modular Dirichlet Energy (MDE) which allows robust and flexible analysis of the functional network with unprecedented temporal precision. We find that connectivity in the Bind condition is less integrated with the global network than in the Shape condition in occipital and frontal modules during the encoding period of the right screen condition. Using MDE we are able to discern driving effects in the occipital module between 100-140ms, coinciding with the P100 visually evoked potential, followed by a driving effect in the frontal module between 140-180ms, suggesting that the differences found constitute an information processing difference between these modules. This provides temporally precise information over a heterogeneous population in promising tasks for the detection of AD.

Published
2016
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23. Comparison of Network Analysis Approaches on EEG Connectivity in Beta during Visual Short-Term Memory Binding Tasks

Author

Smith, Keith, Azami, Hamed, Parra, Mario A., Escudero, Javier, and Starr, John M.

Subjects
Quantitative Biology - Neurons and Cognition
Abstract

We analyse the electroencephalogram signals in the beta band of working memory representation recorded from young healthy volunteers performing several different Visual Short-Term Memory (VSTM) tasks which have proven useful in the assessment of clinical and preclinical Alzheimer's disease. We compare network analysis using Maximum Spanning Trees (MSTs) with network analysis obtained using 20% and 25% connection thresholds on the VSTM data. MSTs are a promising method of network analysis negating the more classical use of thresholds which are so far chosen arbitrarily. However, we find that the threshold analyses outperforms MSTs for detection of functional network differences. Particularly, MSTs fail to find any significant differences. Further, the thresholds detect significant differences between shape and shape-colour binding tasks when these are tested in the left side of the display screen, but no such differences are detected when these tasks are tested for in the right side of the display screen. This provides evidence that contralateral activity is a significant factor in sensitivity for detection of cognitive task differences., Comment: Proceeds from the IEEE Engineering in Medicine and Biology Conference 2015

Published
2016
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24. Cluster-Span Threshold: An unbiased threshold for binarising weighted complete networks in functional connectivity analysis

Author

Smith, Keith, Azami, Hamed, Parra, Mario A., Starr, John M., and Escudero, Javier

Subjects
Quantitative Biology - Neurons and Cognition
Abstract

We propose a new unbiased threshold for network analysis named the Cluster-Span Threshold (CST). This is based on the clustering coefficient, C, following logic that a balance of `clustering' to `spanning' triples results in a useful topology for network analysis and that the product of complementing properties has a unique value only when perfectly balanced. We threshold networks by fixing C at this balanced value, rather than fixing connection density at an arbitrary value, as has been the trend. We compare results from an electroencephalogram data set of volunteers performing visual short term memory tasks of the CST alongside other thresholds, including maximum spanning trees. We find that the CST holds as a sensitive threshold for distinguishing differences in the functional connectivity between tasks. This provides a sensitive and objective method for setting a threshold on weighted complete networks which may prove influential on the future of functional connectivity research., Comment: conference paper from the IEEE Engineering in Medicine and Biology Conference 2015

Published
2016
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27. Saturated Fatty Acids in Wool as Markers Related to Intramuscular Fat Content in Lambs.

Author

Inostroza, Karla, Larama, Giovanni, Díaz-Matus de la Parra, Mario, Bravo, Silvana, Rodríguez, Romina, Guerrero, Ana, and Cancino-Baier, David

Subjects
SATURATED fatty acids, NEAR infrared spectroscopy, MEAT quality, CONSUMER preferences, DISCRIMINANT analysis, ERECTOR spinae muscles
Abstract

Simple Summary: Intramuscular fat (IMF) is related to meat quality and consumer preferences. Several analytical methods involving solvents have been developed to determine IMF and are used to validate rapid and nondestructive new technologies, such as tomography, Raman spectroscopy and NIR. The current study assessed the fatty acid (FA) composition of wool and its relationship to IMF in the Longissimus lumborum muscle of lambs. Wool has the potential for non-invasive sampling, reflecting the animal's metabolism over the past 2 or 3 weeks, and can be stored for long periods of time. The results of this experiment suggest that saturated FA in wool could potentially be used to determine the IMF of lamb. The aim of this study was to identify Longissimus lumborum (LL) muscle from lambs with high IMF content (≥3%) using wool FA. The FA composition was characterized in two sections of wool from Suffolk Down lambs, and its relationship with IMF content assessed. One hundred and forty lambs of similar body weight, body condition score, and age were selected. IMF content from LL muscle, and the wool fat and FA composition of the wool were determined. The proportions of FAs in the wool of lambs with low IMF were 51.96 ± 7.3% of saturated, 31.96 ± 7.7% polyunsaturated, and 16.08 ± 2.3% monounsaturated. Similar proportions of FAs were observed in wool samples of lambs with high IMF. Significant differences were found only in the SFA proportion between groups (p < 0.05). The predominant FAs in the wool samples were C16:0, C17:0, C18:0, C18:1n9c and C18:2n6c, representing over 60% of total FA methyl esters. Correlations were found between the wool FAs C16:1, C17:0, C18:0, C18:1n9c, C24:0, and C22:6n3 in wool samples divided into two sections. Discriminant analysis identified SFAs, particularly FAs C22:0 and C24:0, as potential candidate for predicting lambs with high IMF content with an accuracy of over 92%. These results provide to our knowledge evidence that IMF content could potentially be determined using wool FAs as a non-invasive method. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City

Author

Sosa, Ana Luisa, primary, Brucki, Sonia MD, additional, Crivelli, Lucia, additional, Lopera, Francisco Javier, additional, Acosta, Daisy M, additional, Acosta‐Uribe, Juliana, additional, Aguilar, Diego, additional, Aguilar‐Navarro, Sara G, additional, Allegri, Ricardo F, additional, Bertolucci, Paulo HF, additional, Calandri, Ismael L, additional, Carrillo, Maria C, additional, Mendez, Patricio Alexis Chrem, additional, Cornejo‐Olivas, Mario, additional, Custodio, Nilton, additional, Damian, Andrés, additional, de Souza, Leonardo Cruz, additional, Duran‐Aniotz, Claudia, additional, García, Adolfo M, additional, García‐Peña, Carmen, additional, Gonzales, Mitzi M, additional, Grinberg, Lea T, additional, Ibanez, Agustin M, additional, Illanes‐Manrique, Maryenela Zaida, additional, Jack, Clifford R, additional, Leon‐Salas, Jorge Mario, additional, Llibre‐Guerra, Jorge J, additional, Luna‐Muñoz, José, additional, Matallana, Diana, additional, Miller, Bruce L, additional, Naci, Lorina, additional, Parra, Mario A, additional, Pericak‐Vance, Margaret, additional, Piña‐Escudero, Stefanie D, additional, França Resende, Elisa de Paula, additional, Ringman, John M, additional, Sevlever, Gustavo, additional, Slachevsky, Andrea, additional, Suemoto, Claudia Kimie, additional, Valcour, Victor, additional, Villegas‐Lanau, Andres, additional, Yassuda, Mônica S, additional, Mahinrad, Simin, additional, and Sexton, Claire, additional

Published
2024
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29. The Mediterranean diet is not associated with neuroimaging or cognition in middle‐aged adults: a cross‐sectional analysis of the PREVENT dementia programme

Author

Gregory, Sarah, primary, Buller‐Peralta, Ingrid, additional, Bridgeman, Katie, additional, Góngora, Vanessa De La Cruz, additional, Dounavi, Maria‐Eleni, additional, Low, Audrey, additional, Ntailianis, Georgios, additional, O'Brien, John, additional, Parra, Mario A., additional, Ritchie, Craig W., additional, Ritchie, Karen, additional, Shannon, Oliver M., additional, Stevenson, Emma J., additional, and Muniz‐Terrera, Graciela, additional

Published
2024
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31. Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole‐brain modeling

Author

Coronel‐Oliveros, Carlos, primary, Gómez, Raúl Gónzalez, additional, Ranasinghe, Kamalini, additional, Sainz‐Ballesteros, Agustín, additional, Legaz, Agustina, additional, Fittipaldi, Sol, additional, Cruzat, Josephine, additional, Herzog, Rubén, additional, Yener, Gorsev, additional, Parra, Mario, additional, Aguillon, David, additional, Lopera, Francisco, additional, Santamaria‐Garcia, Hernando, additional, Moguilner, Sebastián, additional, Medel, Vicente, additional, Orio, Patricio, additional, Whelan, Robert, additional, Tagliazucchi, Enzo, additional, Prado, Pavel, additional, and Ibañez, Agustín, additional

Published
2024
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34. Prevalence of Mild Cognitive Impairment in Southern Regions of Colombia

Author

Bonilla-Santos, Jasmin, primary, González-Hernández, Alfredis, additional, Cala-Martínez, Dorian Yisela, additional, Gómez-Morales, Duván Fernando, additional, Calceto-Garavito, Laura Natalia, additional, Forero-Aldana, Arnulfo Eduardo, additional, González-Montealegre, Rodrigo Alberto, additional, Cardona Cumaco, Yeing Alexandra, additional, Rojas-Bernal, Luz Angela, additional, Zabaleta-Orozco, Mario Alberto, additional, and Parra, Mario Alfredo, additional

Published
2023
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37. GERO Cohort Protocol, Chile, 2017–2022: Community-based Cohort of Functional Decline in Subjective Cognitive Complaint elderly

Author

Slachevsky, Andrea, Zitko, Pedro, Martínez-Pernía, David, Forno, Gonzalo, Court, Felipe A., Lillo, Patricia, Villagra, Roque, Duran-Aniotz, Claudia, Parrao, Teresa, Assar, Rodrigo, Orellana, Paulina, Toledo, Carolina, Rivera, Rodrigo, Ibañez, Agustín, Parra, Mario A., González-Billault, Christian, Amieva, Helena, and Thumala, Daniela

Published
2020
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40. Harmonized multi‐metric and multi‐centric assessment of EEG source space connectivity for dementia characterization

Author

Prado, Pavel, primary, Mejía, Jhony A., additional, Sainz‐Ballesteros, Agustín, additional, Birba, Agustina, additional, Moguilner, Sebastian, additional, Herzog, Rubén, additional, Otero, Mónica, additional, Cuadros, Jhosmary, additional, Z‐Rivera, Lucía, additional, O'Byrne, Daniel Franco, additional, Parra, Mario, additional, and Ibáñez, Agustín, additional

Published
2023
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44. Abnormal Functional Hierarchies of EEG Networks in Familial and Sporadic Prodromal Alzheimer's Disease During Visual Short-Term Memory Binding

Author

Smith, Keith M., Starr, John M., Escudero, Javier, Ibáñez, Agustín M, and Parra, Mario Alfredo

Subjects
Aging, Working memory, RC0321, Alzheimer's Disease, electrophysiology, brain networks
Abstract

Alzheimer's Disease (AD) shows both complex alterations of functional dependencies between brain regions and a decreased ability to perform Visual Short-Term Memory Binding (VSTMB) tasks. Recent advances in network neuroscience toward understanding the complexity of hierarchical brain function here enables us to establish a link between these two phenomena. Here, we study data on two types of dementia at Mild Cognitive Impairment (MCI) stage—familial AD patients (E280A mutation of the presenilin-1 gene) and elderly MCI patients at high risk of sporadic AD, both with age-matched controls. We analyzed Electroencephalogram (EEG) signals recorded during the performance of Visual Short-Term Memory (VSTM) tasks by these participants. Functional connectivity was computed using the phase-lag index in Alpha and Beta; and network analysis was employed using network indices of hierarchical spread (degree variance) and complexity. Hierarchical characteristics of EEG functional connectivity networks revealed abnormal patterns in familial MCI VSTMB function and sporadic MCI VSTMB function. The middle-aged familial MCI binding network displayed a larger degree variance in lower Beta compared to healthy controls (p = 0.0051, Cohen's d = 1.0124), while the elderly sporadic MCI binding network displayed greater hierarchical complexity in Alpha (p = 0.0140, Cohen's d = 1.1627). Characteristics in healthy aging were not shown to differ. These results indicate that activity in MCI exhibits cross-frequency network reorganization characterized by increased heterogeneity of node roles in the functional hierarchy. Aging itself is not found to cause VSTM functional hierarchy differences.

Published
2022
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45. Tracing brain amyloid-β in asymptomatic older adults relying on a memory marker for Alzheimer's disease

Author

Parra, Mario A., Gazes, Yunglin, Habeck, Christian, and Stern, Yaakov

Subjects
RC0321
Abstract

Recent approaches to the early diagnosis of Alzheimer’s disease (AD) are aimed at detecting neuropathological signatures of this type of dementia in still healthy older adults. Should these efforts prove fruitful, strategies then focus on identifying the cognitive and functional decline that ensue. These approaches have proved both little effective and costly. In the present study, we investigated the hypothesis that effective cognitive markers for AD could help detect among still healthy older adults who would have likely started to accumulate the neuropathological changes pursued by costly neuroimaging procedures. A sample of 39 healthy older adults was recruited and assessed with an extensive neuropsychological and neuroimaging protocol. As the memory marker, we used the Visual Short-Term Memory Binding Task. Using existing data, participants were divided in two groups depending on whether or not they displayed the typical binding profile seen in AD subjects (i.e., strong binders – SB and weak binders - WB). The results show that in addition to the increased binding cost seen in WB, SB and WB could only be differentiated by the amount of Amyloid- accumulated in brain regions known to be involved in this cognitive function. No other neuropsychological tests proved informative, and neither volumetric nor cortical thickness metrics provided meaningful neuropathological signals. Our findings have significant implications for our understanding of the transition from normal ageing to preclinical AD and methodological approaches currently used to ascertain it. These are discussed at length.

Published
2022

46. Short-term memory conjunctive binding in Alzheimer's disease : a systematic review and meta-analysis

Author

Cecchini, Mario Amore, Parra, Mario A., Brazzelli, Miriam, Logie, Robert H., and Sala, Sergio Della

Subjects
RC0321, BF
Abstract

Objective: Short-term memory (STM) binding tests assess the ability to temporarily hold conjunctions between surface features, such as objects and their colors (i.e., feature binding condition), relative to the ability to hold the individual features (i.e., single feature condition). Impairments in performance of these tests have been considered cognitive markers of Alzheimer's disease (AD). The objective of the present study was to conduct a meta-analysis of results from STM binding tests used in the assessment of samples mapped along the AD clinical continuum. Methods: We searched PubMed, Scopus and Web of Science for articles that assessed patients with AD (from preclinical to dementia) using the STM binding tests and compared their results with those of controls. From each relevant article, we extracted the number of participants, the mean and standard deviations from single feature and of feature binding conditions. Results across studies were combined using standardized mean differences (effect sizes) to produce overall estimates of effect. Results: The feature binding condition of the STM binding showed large effects in all stages of AD. However, small sample sizes across studies, the presence of moderate to high heterogeneity and cross-sectional, case-controls designs decreased our confidence in the current evidence. Conclusions: To be considered as a cognitive marker for AD, properly powered longitudinal designs and studies that clearly relate conjunctive memory tests with biomarkers (amyloid and tau) are still needed.

Published
2022

47. Treatment effects on event-related EEG potentials and oscillations in Alzheimer's disease

Author

Yener, Görsev, Hünerli-Gündüz, Duygu, Yıldırım, Ebru, Aktürk, Tuba, Başar-Eroğlu, Canan, Bonanni, Laura, Del Percio, Claudio, Farina, Francesca, Ferri, Raffaele, Güntekin, Bahar, Hajós, Mihály, Ibáñez, Agustín, Jiang, Yang, Lizio, Roberta, Lopez, Susanna, Noce, Giuseppe, Parra, Mario, Randall, Fiona, Stocchi, Fabrizio, Babiloni, Claudio, Yener, Görsev, Hünerli-Gündüz, Duygu, Yıldırım, Ebru, Aktürk, Tuba, Başar-Eroğlu, Canan, Bonanni, Laura, Del Percio, Claudio, Farina, Francesca, Ferri, Raffaele, Güntekin, Bahar, Hajós, Mihály, Ibáñez, Agustín, Jiang, Yang, Lizio, Roberta, Lopez, Susanna, Noce, Giuseppe, Parra, Mario, Randall, Fiona, Stocchi, Fabrizio, and Babiloni, Claudio

Abstract

Alzheimer's disease dementia (ADD) is the most diffuse neurodegenerative disorder belonging to mild cognitive impairment (MCI) and dementia in old persons. This disease is provoked by an abnormal accumulation of amyloid-beta and tauopathy proteins in the brain. Very recently, the first disease-modifying drug has been licensed with reserve (i.e., Aducanumab). Therefore, there is a need to identify and use biomarkers probing the neurophysiological underpinnings of human cognitive functions to test the clinical efficacy of that drug. In this regard, event-related electroencephalographic potentials (ERPs) and oscillations (EROs) are promising candidates. Here, an Expert Panel from the Electrophysiology Professional Interest Area of the Alzheimer's Association and Global Brain Consortium reviewed the field literature on the effects of the most used symptomatic drug against ADD (i.e., Acetylcholinesterase inhibitors) on ERPs and EROs in ADD patients with MCI and dementia at the group level. The most convincing results were found in ADD patients. In those patients, Acetylcholinesterase inhibitors partially normalized ERP P300 peak latency and amplitude in oddball paradigms using visual stimuli. In these same paradigms, those drugs partially normalize ERO phase-locking at the theta band (4-7 Hz) and spectral coherence between electrode pairs at the gamma (around 40 Hz) band. These results are of great interest and may motivate multicentric, double-blind, randomized, and placebo-controlled clinical trials in MCI and ADD patients for final cross-validation.

Published
2022

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

Author

Grandi, Fabrissio, primary, Martínez-Pernía, David, additional, Parra, Mario, additional, Olavarria, Loreto, additional, Huepe, David, additional, Alegria, Patricia, additional, Aliaga, Álvaro, additional, Lillo, Patricia, additional, Delgado, Carolina, additional, Tenorio, Marcela, additional, Rosas, Ricardo, additional, López, Oscar, additional, Becker, James, additional, and Slachevsky, Andrea, additional

Published
2022
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50. Memory markers can help trace the Alzheimer’s disease continuum: Evidence from the GERO Cohort

Author

Forno, Gonzalo, Parra, Mario A, Lillo, Patricia, Villagra, Roque, Parrao, Teresa, Thumala, Daniela, and Slachevsky, Andrea

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, RC0321, Neurology (clinical), Geriatrics and Gerontology
Abstract

Background: Cognitive assessments able to detect impairments as early as neuropathological changes that occur in neurodegenerative diseases initiate are urgently needed. The Visual Short-Term Memory Binding Test (VSTMBT) and the Free and Cued Selective Reminding Test (FCRST) have been recently recommended by the Neurodegenerative Diseases Working Group (Costa et al., 2017) as promising preclinical markers of AD. They have never been used before to assess elderlies with cognitive complain recruited from the community. Method: A total of 271 subjects (37 healthy controls (HC), 112 subjective cognitive complain (SCC), 96 mild cognitive impairment (MCI) and 26 Alzheimer's disease dementia (ADD)), recruited from Geroscience Center for Brain Health and Metabolism (GERO) Cohort and the Memory and Neuropsychiatric Clinic (CMYN), underwent assessment with the VSTMBT and the Visual Version of the FCRST (FCRST-Visual). Two memory loads were used for the VSTMBT (low and high). The ability of these tests to discriminate between groups. Result: Significant differences were found between HC, MCI and ADD using the VSTMBT and the FCRST-Visual version. Notably, the STMB was the only test that "marginally" differentiated between HC from SCC (p = 0.055). Moreover, whereas the FCRST-Visual showed a gradient (HC = SCC) > MCI > AD, the VSTMBT's gradient was HC > (SCC = MCI = ADD) suggesting that the function assessed by the latter test may be sensitive to the very early stages of the disease dropping to levels that cannot decline further. Conclusion: Our results suggest that the VSTMBT and FCSRT are sensitive to the early stages of dementia. Whereas the former detects changes in the early subjective stages, the latter is more sensitive to later objective stages of cognitive decline. The latter but not the former could help monitor disease progression. These results raise important questions about the usefulness of cognitive screening tools to detect and monitor disease progression and to separate normal and abnormal ageing trajectories. We propose the need of cognitive assessments that detect subtle differences as early as neuropathological changes occur in the brain, which will lead to the development of new "cognitive biomarkers" for dementia.

Published
2021
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