“¿Qué es una tortuga? neuropsicología de la demencia semántica”

RESUMEN: La demencia semántica (DS) se caracteriza por la pérdida del conocimiento semántico. Los pacientes presentan un lenguaje fluente con alteración de la comprensión a nivel de palabra y clara anomia. Frecuentemente aparecen trastornos neuropsiquiátricos. La superposición de síntomas cognitivos y neuropsiquiátricos que presenta con otras enfermedades hace muchas veces complejo su diagnóstico. Además, su evaluación suele requerir del lenguaje hablado y muchas veces los pacientes con DS presentan alteración en esta área. Los objetivos fueron: 1º, conocer los principales marcadores cognitivos y neuropsiquiátricos que permiten diferenciar la DS de la Enfermedad de Alzheimer (EA) y la Demencia Frontotemporal variante conductual (DFTvc) así como la DS izquierda de la DS derecha; 2º, diseñar una tarea de dibujo sencilla y rápida como prueba de cribado para evaluar el conocimiento semántico; 3º, testar la hipótesis de la retrogénesis, comparando la adquisición de conocimientos que tiene lugar en los niños y la pérdida objetivada en los pacientes con DS mediante una tarea de dibujo breve. Para ello contamos con una muestra de 87 pacientes (35 DS, 32 EA y 20 DFTvc), y 104 niños de entre 40 y 96 meses. Los pacientes fueron sometido a una evaluación neuropsicológica completa y a una entrevista sobre la presencia de sintomatología neuropsiquiátrica. Además, se les administró una tarea de dibujo diseñada por nuestro grupo. El grupo de niños fue evaluado a través de la misma tarea de dibujo. Resultados: los 4 test cognitivos que más ayudaron al diagnóstico diferencial fueron: a) un test de memoria episódica que incluya aprendizaje y recuperación con pistas semánticas, b) una tarea que evalúa prosopagnosia, c) un test de denominación y d) una prueba que mida la capacidad visoespacial. La agresividad, la dejadez en el autocuidado, los hábitos alimenticios, especialmente el aumento de la ingesta y el cambio en las preferencias alimenticias, fueron los síntomas neuropsiquiátricos que mejor rendimiento alcanzaron para la categorización por grupos. Nuestra propuesta de “una tarea de dibujo breve” permite estimar el conocimiento semántico y podría ser una buena herramienta para el diagnóstico diferencial de la DS. Finalmente, se observó que los ítems que los niños más pequeños dibujaron con un mayor nivel de detalle fueron aquellos que los pacientes con DS más avanzada dibujaron de una manera más completa y viceversa. Conclusiones: A pesar de los últimos avances en biomarcadores y técnicas de neuroimagen, este trabajo demuestra la significativa contribución de una exhaustiva y detallada evaluación cognitiva en el diagnóstico diferencial. Nuestro estudio sugiere la utilidad potencial de una tarea de dibujo breve como prueba de cribado para el conocimiento semántico. Finalmente, la adquisición y pérdida del conocimiento semántico en niños y pacientes con DS mediante una tarea de dibujo apoya la teoría de la retrogénesis.ABSTRACT: Semantic dementia (SD) is characterized by the loss of semantic knowledge. Patients present a fluent language with single-word comprehension deficit and anomia. Neuropsychiatric disorders often appear. The overlap of cognitive and neuropsychiatric symptoms with other diseases often makes their diagnosis complex. In addition, their evaluation usually requires spoken language and many times patients with DS present alteration in this area. The objectives were: 1) to know the main cognitive and neuropsychiatric markers that allow differentiating DS from Alzheimer's disease (AD) and behavioral variant Frontotemporal dementia (vbFTD) as well as left DS from right DS; 2) to design a simple and brief drawing task as a screening test to evaluate semantic knowledge; 3) to verify the retrogenesis hypothesis, comparing the knowledge acquisition that takes place in children and the loss objectified in patients with DS by means of a brief drawing task. We recruited a sample of 87 patients (35 SD, 32 AE and 20 VFTD), and 104 children aged between 40 and 96 months. The patients underwent a complete neuropsychological evaluation and an interview about the presence of neuropsychiatric symptoms. In addition, were administered a drawing task designed by our group. The group of children was evaluated through the same drawing task. Results: the 4 cognitive tests that most helped the differential diagnosis were: a) an episodic memory test that included semantic clues, b) a task that evaluates prosopagnosia, c) a naming test and d) a test that measures visuospatial ability. Aggresion, personal care, eating habits, especially specifically over-eating and altered food preference, were the most powerful items for group categorization. Our proposal of "a brief drawing task" allows to estimate the semantic knowledge and could be a good tool for the differential diagnosis of SD. Finally, it was observed that the items that younger children drew with a higher level of detail were those that patients with more advanced DS drew more completely and vice versa. Conclusions: Despite the latest advances in biomarkers and neuroimaging techniques, this work demonstrates the significant contribution of a comprehensive and detailed cognitive assessment in the differential diagnosis. Our study suggests the potential usefulness of a brief drawing task as a screening test for semantic knowledge. Finally, the acquisition and loss of semantic knowledge in children and patients with DS through a drawing task supports the theory of retrogenesis.Esta tesis ha sido cofinanciada por el Instituto de Investigación Sanitaria del Hospital Universitario Marqués de Valdecilla (IDIVAL) y por el Instituto de Salud Carlos III gracias a un contrato predoctoral de Formación en Investigación de Salud (CNV-194)

Exploring the relationship between deficits in social cognition and neurodegenerative dementia: a systematic review

Background: Neurodegenerative diseases might affect social cognition in various ways depending on their components (theory of mind, emotional processing, attribution bias, and social perception) and the subtype of dementia they cause. This review aims to explore this difference in cognitive function among individuals with different aetiologies of dementia. Methods: The following databases were explored: MEDLINE via PubMed, Cochrane Library, Lilacs, Web of Science, and PsycINFO. We selected studies examining social cognition in individuals with neurodegenerative diseases in which dementia was the primary symptom that was studied. The neurodegenerative diseases included Alzheimer's disease, Lewy body disease and frontotemporal lobar degeneration. The search yielded 2,803 articles. Results: One hundred twenty-two articles were included in the present review. The summarised results indicate that people with neurodegenerative diseases indeed have deficits in social cognitive performance. Both in populations with Alzheimer's disease and in populations with frontotemporal dementia, we found that emotional processing was strongly affected. However, although theory of mind impairment could also be observed in the initial stages of frontotemporal dementia, in Alzheimer's disease it was only appreciated when performing highly complex task or in advanced stages of the disease. Conclusions: Each type of dementia has a differential profile of social cognition deterioration. This review could provide a useful reference for clinicians to improve detection and diagnosis, which would undoubtedly guarantee better interventions.FUNDING: This work was supported by a Juan de la Cierva-Formación contract (ESS) from the Spanish Ministry of Science and Innovation (FJC2019-042390-I/AEI/10.13039/501100011033) and a Miguel Servet contract (RAA) from the Carlos III Health Institute (CP18/00003)

Poorer cognitive function and environmental airborne Mn exposure determined by biomonitoring and personal environmental monitors in a healthy adult population

Background/aim: In the Santander Bay (Cantabria, northern Spain), a ferromanganese alloy plant is located. Our objective was to characterize the Mn personal exposure of adult healthy volunteers living in this highly Mn exposed region, and to determine its association with a poorer cognitive function. Methods: Cross-sectional study analyzing 130 consecutive participants. Cognitive function was assessed by Stroop Color Word, Verbal Fluency tests, Trail Making Test (TMT), Digit Span (WAIS III) and Rey Osterrieth Complex Figure (ROCF) tests and crude scores were standardized according to NEURONORMA norms. Exposure to Mn was assessed in terms of source distance, by Personal Environmental Monitors (PEMs) allowing the separation of fine (PM2.5) and coarse (PM10-2.5) particles (obtaining the bioaccessible fraction by in-vitro bioaccessibility tests), and by biomarkers (blood, hair and fingernails). Age, sex, study level and number of years of residence were predefined as confounding variables and adjusted Mean Differences (MDs) were obtained. Results: Statistically significant lower scores (negative MDs) in all test were observed when living near the industrial emission source, after adjusting for the predefined variables. Regarding PEMs results, statistically significant lower scores in all Stroop parts were obtained in participants with higher levels of Total Mn in All fractions (PM10). For Verbal Fluency tests, negative MDs were obtained for both bioaccessible fractions. Digit Span Backward scores were lower for those with higher levels in the bioaccessible coarse fraction, and negative MDs were also observed for the ROCF Delayed part and the non-bioaccessible fine fraction. As regards to Mn in fingernails, adjusted MDs of -1.60; 95%CI (-2.57 to -0.64) and -1.45; 95%CI (-2.29 to -0.61) for Digit Span Forward and Backward parts were observed. Conclusions: Our results support an association between poorer cognitive function and environmental airborne Mn exposure.This work was supported by the Spanish Ministry of Science, Innovation and Universities through the CTM2017-82636-R Project. This funding source was not involved in the study design; data collection, analysis, or interpretation; the writing of the article; or the decision to submit for publication

Sleep time estimated by an actigraphy watch correlates with CSF tau in cognitively unimpaired elders: the modulatory role of APOE

There is increasing evidence of the relationship between sleep and neurodegeneration, but this knowledge is not incorporated into clinical practice yet. We aimed to test whether a basic sleep parameter, as total sleep estimated by actigraphy for 1 week, was a valid predictor of CSF Alzheimer’s Disease core biomarkers (amyloid-β-42 and –40, phosphorylated-tau-181, and total-tau) in elderly individuals, considering possible confounders and effect modifiers, particularly the APOE ε4 allele. One hundred and twenty-seven cognitively unimpaired volunteers enrolled in the Valdecilla Study for Memory and Brain Aging participated in this study. Seventy percent of the participants were women with a mean age of 65.5 years. After adjustment for covariates, reduced sleep time significantly predicted higher t-tau and p-tau. This association was mainly due to the APOE ε4 carriers. Our findings suggest that total sleep time, estimated by an actigraphy watch, is an early biomarker of tau pathology and that APOE modulates this relationship. The main limitation of this study is the limited validation of the actigraphy technology used. Sleep monitoring with wearables may be a useful and inexpensive screening test to detect early neurodegenerative changes.This work was supported by grants from the Instituto de Salud Carlos III (Fondo de Investigación Sanitario, PI08/0139, PI12/02288, PI16/01652, and PI20/01011), the JPND (DEMTEST PI11/03028), the CIBERNED, and the Siemens Healthineer

Cerebral changes and disrupted gray-matter cortical networks in asymptomatic older adults at risk for Alzheimer's disease

The diagnostic value of cerebrospinal fluid (CSF) biomarkers is well established in Alzheimer's disease, but our current knowledge about how abnormal CSF levels affect cerebral integrity, at local and network levels, is incomplete in asymptomatic older adults. Here, we have collected CSF samples and performed structural magnetic resonance imaging scans in cognitively normal elderly as part of a cross-sectional multicenter study (SIGNAL project). To identify group differences in cortical thickness, white matter volume, and properties of structural networks, participants were split into controls (N = 20), positive amyloid-? (A?1?42 +) (N = 19), and positive phosphorylated tau (N = 18). The A?1?42 + group exhibited thickening of middle temporal regions, while positive phosphorylated tau individuals showed thinning in the superior parietal and orbitofrontal cortices. Subjects with abnormal CSF biomarkers further showed regional white matter atrophy and more segregated cortical networks, the A?1?42 + group showing heightened isolation of cingulate and temporal cortices. Collectively, these findings highlight the relevance of combining structural brain imaging and connectomics for in vivo tracking of Alzheimer's disease lesions in asymptomatic stages.This work was supported by research grants from the Spanish Ministry of Economy and Competitiveness (SAF2011-25463 to J.L.C., PSI2014-55747-R to M.A.), the Carlos III Institute of Health, Spain (PI11/02425 and PI14/01126 to J.F.; PI11/3035 and PI14/1561 to A.L.; PI08/0139, PI12/02288 and PI16/01652 to P.S.J.), jointly funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, “Una manera de hacer Europa”, the Joint Programming in Neurodegenerative Disease Research (DEMTEST to P.S.J.), “Marató TV3” (project 20141210 to J.F. and 20142610 to A.L.), the Regional Ministry of Innovation, Science and Enterprise, Junta de Andalucia (P12- CTS-2327 to J.C.L.), and the CIBERNED program (Signal project)

Accuracy of plasma Abeta40, Abeta42, and p-tau181 to detect CSF Alzheimer's pathological changes in cognitively unimpaired subjects using the Lumipulse automated platform

Background The arrival of new disease-modifying treatments for Alzheimer’s disease (AD) requires the identifca tion of subjects at risk in a simple, inexpensive, and non-invasive way. With tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is neces sary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fuid or PET imaging. With this research, we want to evaluate the performance of plasma Aβ40, Aβ42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform. Methods Both plasma and CSF Aβ40, Aβ42, and p-tau181 have been evaluated in a group of 208 cognitively unim paired subjects with a 30.3% of ApoE4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the diferences in plasma marker values according to amyloid status (A−/+), AD status (consider ing AD+subjects to those A+plus Tau+), and ATN group defned by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and diferent combinations of plasma markers as predictors. Results Aβ42, amyloid ratio, p-tau181, and p-tau181/Aβ42 ratio correlated signifcantly between plasma and CSF. For these markers, the levels were signifcantly diferent in the A+/−, AD+/−, and ATN groups. Amyloid ratio pre dicts amyloid and AD pathology in CSF with an AUC of 0.89. Conclusions Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer’s pathology in cognitively unimpaired subjects