Clinical manifestations of geriatric depression in a memory clinic: Toward a proposed subtyping of geriatric depression

BACKGROUND: As the older population increases so does the number of older psychiatric patients. Elderly psychiatric patients manifest certain specific and unique characteristics. Different subtypes of depressive syndromes exist in late-life depression, and many of these are associated with cognitive impairment. MATERIALS AND METHODS: A total of 109 depressive patients and 30 normal subjects matched by age and educational level were evaluated using a neuropsychiatric interview and an extensive neuropsychological battery. Depressive patients were classified into four different groups by SCAN 2.1 (schedules for clinical assessment in Neuropsychiatry): major depression disorder (n: 34), dysthymia disorder (n: 29), subsyndromal depression (n: 28), and depression due to mild dementia of Alzheimer's type (n: 18). RESULTS: We found significant associations (p<.05) between depressive status and demographic or clinical factors that include marital status (OR: 3.4, CI: 1.2-9.6), level of daily activity (OR: 5.3, CI: 2-14), heart disease (OR: 12.5, CI: 1.6-96.3), and high blood cholesterol levels (p:.032). Neuropsychological differences were observed among the four depressive groups and also between depressive patients and controls. Significant differences were observed in daily life activities and caregivers' burden between depressive patients and normal subjects. CONCLUSION: Geriatric depression is associated with heart disease, high cholesterol blood levels, marital status, and daily inactivity. Different subtypes of geriatric depression have particular clinical features, such as cognitive profiles, daily life activities, and caregivers' burden, that can help to differentiate among them. LIMITATIONS: The cohort referred to a memory clinic with memory complaints is a biased sample, and the results cannot be generalized to other non-memory symptomatic cohorts.Fil: Dillon, Carol. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; ArgentinaFil: MacHnicki, Gerardo. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; ArgentinaFil: Serrano, Cecilia M.. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; ArgentinaFil: Rojas, Galeno. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; ArgentinaFil: Vazquez, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; ArgentinaFil: Allegri, Ricardo Francisco. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Alterations to cerebral perfusion, metabolite profiles, and neuronal morphology in the hippocampus and cortex of male and female mice during chronic exposure to a high-salt diet

Excess dietary salt reduces resting cerebral blood flow (CBF) and vascular reactivity, which can limit the fueling of neuronal metabolism. It is hitherto unknown whether metabolic derangements induced by high-salt-diet (HSD) exposure during adulthood are reversed by reducing salt intake. In this study, male and female mice were fed an HSD from 9 to 16 months of age, followed by a normal-salt diet (ND) thereafter until 23 months of age. Controls were continuously fed either ND or HSD. CBF and metabolite profiles were determined longitudinally by arterial spin labeling magnetic resonance imaging and magnetic resonance spectroscopy, respectively. HSD reduced cortical and hippocampal CBF, which recovered after dietary salt normalization, and affected hippocampal but not cortical metabolite profiles. Compared to ND, HSD increased hippocampal glutamine and phosphocreatine levels and decreased creatine and choline levels. Dietary reversal only allowed recovery of glutamine levels. Histology analyses revealed that HSD reduced the dendritic arborization and spine density of cortical and hippocampal neurons, which were not recovered after dietary salt normalization. We conclude that sustained HSD exposure throughout adulthood causes permanent structural and metabolic alterations to the mouse brain that are not fully normalized by lowering dietary salt during aging

Multivariate word properties in fluency tasks reveal markers of Alzheimer’s dementia

Version of Record online: 12 October 2023INTRODUCTION Verbal fluency tasks are common in Alzheimer's disease (AD) assessments. Yet, standard valid response counts fail to reveal disease-specific semantic memory patterns. Here, we leveraged automated word-property analysis to capture neurocognitive markers of AD vis-à-vis behavioral variant frontotemporal dementia (bvFTD). METHODS Patients and healthy controls completed two fluency tasks. We counted valid responses and computed each word's frequency, granularity, neighborhood, length, familiarity, and imageability. These features were used for group-level discrimination, patient-level identification, and correlations with executive and neural (magnetic resonanance imaging [MRI], functional MRI [fMRI], electroencephalography [EEG]) patterns. RESULTS Valid responses revealed deficits in both disorders. Conversely, frequency, granularity, and neighborhood yielded robust group- and subject-level discrimination only in AD, also predicting executive outcomes. Disease-specific cortical thickness patterns were predicted by frequency in both disorders. Default-mode and salience network hypoconnectivity, and EEG beta hypoconnectivity, were predicted by frequency and granularity only in AD. DISCUSSION Word-property analysis of fluency can boost AD characterization and diagnosis. Highlights We report novel word-property analyses of verbal fluency in AD and bvFTD. Standard valid response counts captured deficits and brain patterns in both groups. Specific word properties (e.g., frequency, granularity) were altered only in AD. Such properties predicted cognitive and neural (MRI, fMRI, EEG) patterns in AD. Word-property analysis of fluency can boost AD characterization and diagnosis.National Institutes of Health, National Institutes of Aging, Grant/Award Numbers: R01AG057234, R01AG075775; ANID: FONDECYT Regular, Grant/Award Numbers: 1210176, 1210195, 1220995; FONDAP, Grant/Award Number: 15150012; PIA/ANILLOS, Grant/Award Number: ACT210096; FONDEF, Grant/Award Number: ID20I10152; GBHI, Alzheimer’s Association, and Alzheimer’s Society: Alzheimer’s Association GBHI, Grant/Award Number: ALZ UK-22-865742; Alzheimer’s Association, Grant/Award Number: SG-20-725707; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibáñez, Santiago, Chile, Grant/Award Number: #BL-SRGP2021-01; Programa Interdisciplinario de Investigación Experimental en Comunicación y Cognición (PIIECC), Facultad de Humanidades, USACH; Takeda, Grant/Award Number: CW2680521; Rainwater Charitable Foundation; Tau Consortium; European Commission: H2020-MSCA-IF-GFMULTI-LAND, Grant/Award Number: 10102581

Multimodal mechanisms of human socially reinforced learning across neurodegenerative diseases

Social 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.Fil: Legaz, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Abrevaya, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Dottori, Martín. Universidad de San Andrés; ArgentinaFil: Campo, Cecilia González. Universidad de San Andrés; ArgentinaFil: Birba, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; ArgentinaFil: Martorell Caro, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Aguirre, María Julieta. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; ArgentinaFil: Slachevsky, Andrea. Universidad de Chile.; ChileFil: Aranguiz, Rafael. Instituto Nacional de Geriatría; ChileFil: Serrano, Cecilia Mariela. Unidad Asistencial "Dr. César Milstein"; ArgentinaFil: Gillan, Claire M.. University of California; Estados UnidosFil: Leroi, Iracema. University of California; Estados UnidosFil: García, Adolfo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; Argentina. University of California; Estados Unidos. Trinity College; Estados Unidos. Universidad Nacional de Cuyo; Argentina. Universidad de Santiago de Chile; ChileFil: Fittipaldi, Sol. Universidad de San Andrés; ArgentinaFil: Ibañez, Agustin Mariano. Universidad de San Andrés; Argentina. University of California; Estados Unidos. Trinity College; Estados Unidos. Universidad Adolfo Ibañez; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Plurilingüismo y aprendizaje cooperativo en el diseño de prácticas de Lingüística

Este artículo presenta el trabajo realizado desde el área de Lingüística General de la Universidad de Alicante para ofertar sus prácticas de la asignatura “Lingüística General II”, común a todas las especialidades de lenguas modernas de la Facultad de Filosofía y Letras, en los tres idiomas en que tiene lugar la docencia de dichas clases: castellano, valenciano e inglés. A fin de armonizar los contenidos prácticos de una enseñanza trilingüe, por un lado, y de fomentar la implicación del alumnado en las actividades prácticas y contribuir al desarrollo del aprendizaje colaborativo en el aula, por otro, los profesores de este área de conocimiento, junto con la participación de dos estudiantes, han diseñado veinte prácticas que van desde el análisis del signo lingüístico hasta la Pragmática, pasando por la Fonética, la Morfología, la Sintaxis y el Análisis del Discurso

Activation of p21 limits acute lung injury and induces early senescence after acid aspiration and mechanical ventilation

The p53/p21 pathway is activated in response to cell stress. However, its role in acute lung injury has not been elucidated. Acute lung injury is associated with disruption of the alveolo-capillary barrier leading to acute respiratory distress syndrome (ARDS). Mechanical ventilation may be necessary to support gas exchange in patients with ARDS, however, high positive airway pressures can cause regional overdistension of alveolar units and aggravate lung injury. Here, we report that acute lung injury and alveolar overstretching activate the p53/p21 pathway to maintain homeostasis and avoid massive cell apoptosis. A systematic pooling of transcriptomic data from animal models of lung injury demonstrates the enrichment of specific p53- and p21-dependent gene signatures and a validated senescence profile. In a clinically relevant, murine model of acid aspiration and mechanical ventilation, we observed changes in the nuclear envelope and the underlying chromatin, DNA damage and activation of the Tp53/p21 pathway. Absence of Cdkn1a decreased the senescent response, but worsened lung injury due to increased cell apoptosis. Conversely, treatment with lopinavir/ritonavir led to Cdkn1a overexpression and ameliorated cell apoptosis and lung injury. The activation of these mechanisms was associated with early markers of senescence, including expression of senescence-related genes and increases in senescence-associated heterochromatin foci in alveolar cells. Autopsy samples from lungs of patients with ARDS revealed increased senescence-associated heterochromatin foci. Collectively, these results suggest that acute lung injury activates p53/p21 as an anti-apoptotic mechanism to ameliorate damage, but with the side effect of induction of senescence

Endosymbiosis in trypanosomatids: the genomic cooperation between bacterium and host in the synthesis of essential amino acids is heavily influenced by multiple horizontal gene transfers

Background Trypanosomatids of the genera Angomonas and Strigomonas live in a mutualistic association characterized by extensive metabolic cooperation with obligate endosymbiotic Betaproteobacteria. However, the role played by the symbiont has been more guessed by indirect means than evidenced. Symbiont-harboring trypanosomatids, in contrast to their counterparts lacking symbionts, exhibit lower nutritional requirements and are autotrophic for essential amino acids. To evidence the symbiont’s contributions to this autotrophy, entire genomes of symbionts and trypanosomatids with and without symbionts were sequenced here. Results Analyses of the essential amino acid pathways revealed that most biosynthetic routes are in the symbiont genome. By contrast, the host trypanosomatid genome contains fewer genes, about half of which originated from different bacterial groups, perhaps only one of which (ornithine cyclodeaminase, EC:4.3.1.12) derived from the symbiont. Nutritional, enzymatic, and genomic data were jointly analyzed to construct an integrated view of essential amino acid metabolism in symbiont-harboring trypanosomatids. This comprehensive analysis showed perfect concordance among all these data, and revealed that the symbiont contains genes for enzymes that complete essential biosynthetic routes for the host amino acid production, thus explaining the low requirement for these elements in symbiont-harboring trypanosomatids. Phylogenetic analyses show that the cooperation between symbionts and their hosts is complemented by multiple horizontal gene transfers, from bacterial lineages to trypanosomatids, that occurred several times in the course of their evolution. Transfers occur preferentially in parts of the pathways that are missing from other eukaryotes. Conclusion We have herein uncovered the genetic and evolutionary bases of essential amino acid biosynthesis in several trypanosomatids with and without endosymbionts, explaining and complementing decades of experimental results. We uncovered the remarkable plasticity in essential amino acid biosynthesis pathway evolution in these protozoans, demonstrating heavy influence of horizontal gene transfer events, from Bacteria to trypanosomatid nuclei, in the evolution of these pathways

Herramientas informáticas orientadas a la enseñanza y el aprendizaje

El amplio abanico de posibilidades tecnológicas disponible en la actualidad no siempre es aprovechado al máximo en el contexto educativo. En esta línea de investigación se propone explotar nuevas formas de aplicar los recursos disponibles para facilitar tanto al docente la transmisión del conocimiento así como al alumno poder adquirirlo, buscando desarrollar nuevas herramientas informáticas que simplifiquen el armado del material usado tanto dentro de sus clases así como de referencia para su posterior estudio fuera del aula. También se proponen herramientas orientadas a aportar dinamismo a las explicaciones del docente, aprovechando la disponibilidad de computadoras cada vez más potentes que permiten la obtención de resultados casi instantáneos al realizar tareas complejas, buscando así clases que sean interactivas, donde la participación de los alumnos adquiera un rol protagónico y no solo sean receptores en una comunicación unidireccional.Eje: Tecnología Informática Aplicada en EducaciónRed de Universidades con Carreras en Informática (RedUNCI