Cultural validity of cognitive markers for Alzheimer's disease (AD) : evidence for global strategies

Background: Availability of culture-free cognitive tests with marker properties for AD has proved a barrier to global harmonization strategies. The European Neurodegenerative Diseases Working Group suggested that the Short-Term Memory Binding Test (STMBT) and the Free and Cued Selective Reminding Test (FCSRT) are useful tests for the early detection of AD (Costa et al., 2017). Yassuda et al. (2019) showed that STMB is insensitive to age and education among healthy Brazilian adults. Parra et al. (2019) suggested that these tests should enter global strategies to aid the early detection of AD. Evidence is still needed to ascertain that such a validity translates to the assessment of affected individuals from underrepresented populations. The current study aimed to shed new light on such an outstanding question. Methods: We recruited 64 healthy controls (HC), 60 patients with Mild Cognitive Impairment (MCI), and 63 patients with mild AD from [Lima at the regional area health clinics of the “Dirección Regional de Salud (DIRESA)” of the “Gobierno Regional del Callao” between June 2018 and May 2019]. They were all illiterate. We considered Illiterate individuals who (1) attended no school or were enrolled for less than one year and (2) could not read or write (a booklet was given which showed a simple sentence). We assessed them with the STMBT, the visual FCSRT, and a brief clinical-neuropsychological protocol. Results: The assessment confirmed the healthy (CDR=0.0, pFAQ=2.2, BDI=5.9), MCI (CDR=0.5, pFAQ=3.7, BDI=6.2), and dementia (CDR=1.3, pFAQ=16.5, BDI=7.2) status of our groups. Significant between-group differences were found with both the STMBT (F(2,184)=590.1, p>>MCI>>>AD. ROC analysis with STMB revealed AUC=0.98 for HC vs. MCI, AUC=1.00 for HC vs. AD, and AUC=0.97 for MCI vs. AD. For the visual FCSRT, an AUC=1.00 was found for HC vs (MCI & AD), and AUC=0.99 for MCI vs AD. Conclusion: The two cognitive markers recently recommended for harmonisation of neuropsychological assessment in neurodegenerative dementias in Europe seem suitable to support such practices in illiterate populations. Parra et al. (2019) recently suggested that only global strategies will help meet global challenges. Here we provide evidence of cognitive markers for AD that can reliably enter such strategies

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

Objetivo. El diagnóstico diferencial de la variante conductual de la demencia frontotemporal (bvFTD) y La enfermedad de Alzheimer (EA) sigue siendo un desafío en grupos subrepresentados y subdiagnosticados, incluidos los latinos, ya que los biomarcadores avanzados rara vez están disponibles. Directrices recientes para el estudio de demencia destacan el papel fundamental de los biomarcadores. Por lo tanto, nuevos complementarios rentables Se requieren enfoques en entornos clínicos. Acercarse. Desarrollamos un marco novedoso basado en un clasificador de aprendizaje automático que aumenta el gradiente, ajustado por la optimización bayesiana, en una función múltiple enfoque multimodal (que combina imágenes demográficas, neuropsicológicas y de resonancia magnética) (IRM) y electroencefalografía/datos de conectividad de IRM funcional) para caracterizar neurodegeneración utilizando la armonización del sitio y la selección de características secuenciales. Evaluamos 54 DFTvc y 76 pacientes con EA y 152 controles sanos (HC) de un consorcio latinoamericano (ReDLat). Resultados principales. El modelo multimodal arrojó una alta clasificación de área bajo la curva (pacientes con DFTvc frente a HC: 0,93 (±0,01); pacientes con EA frente a HC: 0,95 (±0,01); DFTvv frente a EA pacientes: 0,92 (±0,01)). El enfoque de selección de características filtró con éxito información no informativa marcadores multimodales (de miles a decenas). Resultados. Probado robusto contra multimodal heterogeneidad, variabilidad sociodemográfica y datos faltantes. Significado. El modelo con precisión subtipos de demencia identificados utilizando medidas fácilmente disponibles en entornos subrepresentados, con un rendimiento similar al de los biomarcadores avanzados. Este enfoque, si se confirma y replica, puede complementar potencialmente las evaluaciones clínicas en los países en desarrollo.Q1Q1Abstract Objective. 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.https://orcid.org/0000-0001-6529-7077https://scholar.google.com/citations?hl=es&user=kaGongoAAAAJ&view_op=list_works&sortby=pubdatehttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000055000Revista Internacional - IndexadaS

Comparing moral judgments of patients with frontotemporal dementia and frontal stroke

Importance Several clinical reports have stated that patients with prefrontal lesions or patients with the behavioral variant of frontotemporal dementia share social cognition impairments. Moral reasoning is impaired in both conditions but there have been few investigations that directly compare this domain in the 2 groups. Observations This work compared the moral judgments of these patient groups using a task designed to disentangle the contributions of intentions and outcomes in moral judgment. For both disorders, patients judged scenarios where the protagonists believed that they would cause harm but did not as being more permissible than the control group. Moreover, patients with frontotemporal dementia judged harmful outcomes in the absence of harmful intentions as less permissible than the control participants. There were no differences between the 2 conditions. Conclusions and Relevance Both disorders involved impairments in integrating intention and outcome information for moral judgment. This study was the first, to our knowledge, to directly compare a social cognition domain in 2 frontal pathologies with different etiology. Our results highlighted the importance of comparing patients with vascular lesions and patients with neurodegenerative diseases

Apathy, executive function, and emotion recognition re the main drivers of functional ompairment in behavioral variant of Frontotemporal Dementia

Health and self-regulatio

Validation of Picture Free and Cued Selective Reminding Test for Illiteracy in Lima, Peru

Dementia 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 Peru

The 'when' matters : evidence from memory markers in the clinical continuum of Alzheimer's disease

Objective: Cognitive assessment able to detect impairments in the early neuropathological stages of Alzheimer's disease (AD) are urgently needed. The Visual Short-Term Memory Binding Task (VSTMBT) and the Free and Cued Selective Reminding Test (FCSRT) have been recommended by the Neurodegenerative Disease Working Group as promising tests to aid in the early detection of AD. In this study, we investigated their complementary value across the clinical stages of the AD continuum. Methods: 117 older adults with subjective cognitive complaint (SCC), 79 with mild cognitive impairment (MCI), 31 patients with AD dementia (ADD) and 37 cognitively unimpaired (CU) subjects, underwent assessment with the VSTMBT and the Picture version of the Spanish FCSRT. Results: After controlling for multiple comparisons, significant differences were found across groups. The VSTMBT was the only test that ‘marginally’ differentiated between CU and SCC (d = 0.47, p = 0.052). Moreover, whereas the FCSRT showed a gradient (CU = SCC) > MCI > ADD, the VSTMBT gradient was CU > SCC > (MCI = ADD) suggesting that conjunctive binding deficits assessed by the latter may be sensitive to the very early stages of the disease. Conclusions: Our results suggest that the VSTMBT and the FCSRT are sensitive to the clinical continuum of AD. Whereas the former detects changes in the early prodromal stages, the latter is more sensitive to the advanced prodromal stages of AD. These novel tests can aid in the early detection, monitor disease progression and response to treatment, and thus support drug development programs

Dementia in Latin America:Assessing the present and envisioning the future

The demographic structure of Latin American countries (LAC) is fast approaching that of developing countries, and the predicted prevalence of dementia in the former already exceeds the latter. Dementia has been declared a global challenge, yet regions around the world show differences in both the nature and magnitude of such a challenge. This article provides evidence and insights on barriers which, if overcome, would enable the harmonization of strategies to tackle the dementia challenge in LAC. First, we analyze the lack of available epidemiologic data, the need for standardizing clinical practice and improving physician training, and the existing barriers regarding resources, culture, and stigmas. We discuss how these are preventing timely care and research. Regarding specific health actions, most LAC have minimal mental health facilities and do not have specific mental health policies or budgets specific to dementia. In addition, local regulations may need to consider the regional context when developing treatment and prevention strategies. The support needed nationally and internationally to enable a smooth and timely transition of LAC to a position that integrates global strategies is highlighted. We focus on shared issues of poverty, cultural barriers, and socioeconomic vulnerability. We identify avenues for collaboration aimed to study unique populations, improve valid assessment methods, and generate opportunities for translational research, thus establishing a regional network. The issues identified here point to future specific actions aimed at tackling the dementia challenge in LAC.Alzheimer's Society UK grants AS-R42303 AS-SF-14-008 CONICYT-Fondecyt 117001

Dementia and COVID-19 in New Zealand, Chile, and Germany: A Research Agenda for Cross-Country Learning for Resilience in Health Care Systems

The COVID-19 pandemic has revealed existing gaps in policies, systems and services, stressing the need for concerted global action on healthy aging. Similar to the COVID-19 pandemic, dementia is a challenge for health systems on a global scale. Our hypothesis is that translational potential lies in cross-country learning by involving three high-income countries with distinct geo political-cultural-social systems in Latin America (Chile), the South Pacific (New Zealand) and Eu rope (Germany). Our vision is that such cross-country learning will lead to providing adequate, equitable and sustainable care and support for families living with dementia during a pandemic and beyond. We are proposing a vision for research that takes a multi-disciplinary, strength-based approach at the intersection of health care research, disaster research, global health research and dementia research. We present some insights in support of our hypothesis and proposed research agenda. We anticipate that this research has the potential to contribute towards strengthening and transforming health care systems in times of crises and beyond

Self-Motion Holds a Special Status in Visual Processing

Agency plays an important role in self-recognition from motion. Here, we investigated whether our own movements benefit from preferential processing even when the task is unrelated to self-recognition, and does not involve agency judgments. Participants searched for a moving target defined by its known shape among moving distractors, while continuously moving the computer mouse with one hand. They thereby controlled the motion of one item, which was randomly either the target or any of the distractors, while the other items followed pre-recorded motion pathways. Performance was more accurate and less prone to degradation as set size increased when the target was the self-controlled item. An additional experiment confirmed that participant-controlled motion was not physically more salient than motion recorded offline. We found no evidence that self-controlled items captured attention. Taken together, these results suggest that visual events are perceived more accurately when they are the consequences of our actions, even when self-motion is task irrelevant

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

PUBLISHED 25 August 2022Objective. 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.Sebastian Moguilner, Agustina Birba, Sol Fittipaldi, Cecilia Gonzalez-Campo, Enzo Tagliazucchi, Pablo Reyes, Diana Matallana, Mario A Parra, Andrea Slachevsky, Gonzalo Farías, Josefina Cruzat, Adolfo García, Harris A Eyre, Renaud La Joie, Gil Rabinovici, Robert Whelan and Agustín Ibáñe