Effective connectivity of the locus coeruleus in patients with late-life Major Depressive Disorder or mild cognitive impairment.

INTRODUCTION: We compared effective connectivity from the locus coeruleus (LC) during the resting-state in patients with late-life Major Depressive Disorder (MDD), individuals with amnestic Mild Cognitive Impairment (aMCI), and Healthy Controls (HCs). PARTICIPANTS: 23 patients with late-life MDD, 22 patients with aMCI, and 28 HCs. MATERIAL AND METHODS: Participants were assessed in two time-points, 2 years apart. They underwent a resting-state functional magnetic resonance imaging and a high-resolution anatomical acquisition, as well as clinical assessments. Functional imaging data were analyzed with dynamic causal modeling, and parametric empirical Bayes model was used to map effective connectivity between 7 distinct nodes: 4 from the locus coeruleus and 3 regions displaying gray matter decreases during the two-year follow-up period. RESULTS: Longitudinal analysis of structural data identified three clusters of larger over-time gray matter volume reduction in patients (MDD+aMCI vs. HCs): the right precuneus, and the visual association and parahippocampal cortices. aMCI patients showed decreased effective connectivity from the left rostral to caudal portions of the LC, while connectivity from the left rostral LC to the parahippocampal cortex increased. In MDD, there was a decline in effective connectivity across LC caudal seeds, and increased connectivity from the left rostral to the left caudal LC seed over time. Connectivity alterations with cortical regions involved cross-hemisphere increases and same-hemisphere decreases. CONCLUSIONS: Our discoveries provide insight into the dynamic changes in effective connectivity in individuals with late-life MDD and aMCI, also shedding light on the mechanisms potentially contributing to the onset of neurodegenerative disorders.

Hospitalización a domicilio para pacientes quirúrgicos ante una pandemia por SARS-CoV-2: nuestra experiencia / Hospitalization at home for surgical patients in the face of a SARS-CoV-2 pandemic: our experience

Introducción: La hospitalización a domicilio para pacientes quirúrgicos (HaDQ) es una al-ternativa a la hospitalización convencional para pacientes quirúrgicos estables clínicamente, que precisen procedimientos de enfermería complejos por intensidad, frecuencia o carac-terísticas, y control por especialista quirúrgico en el domicilio.Método: Estudio transversal, descriptivo y retrospectivo de la actividad de la HADQ de nuestro hospital durante los primeros seis me-ses del 2020, para analizar la repercusión de la pandemia por SARS-CoV-2 en la unidad. Se distinguen tres periodos: prepandemia (enero-febreo), confinamiento (marzo-abril), poscon-finamiento (mayo-junio). Se diferencian dos grupos: A (HaD convencional) y B (despistaje preoperatorio COVID19). Se recogieron diver-sas variables: mes, tipo, estancia (HaD y hospi-tal), procedimientos, reingresos, domicilio, tipo visitas, COVID+. Se realizó un análisis estadís-tico descriptivo cuantitativo y cualitativo de los resultados obtenidosResultados: Ingresaron 345 pacientes, 225 en el grupo A (fase Pre (34%), fase C (40%), y fase Pos (25%)), y 120 en el B (fase C (75%), fase Pos (25%)). El confinamiento (fase C) fue el pe-ríodo más activo de la HADQ, tanto por número de ingresos (53%), como por la complejidad del grupo A que requería más procedimientos (71%) y más visitas domiciliarias (52%). Tam-bién aumentaron los pacientes de zona de no cobertura (42%), que implicaron visitas médicas y de enfermería en Hospital de Día (HD) (21%), y aumento de consultas telefónicas médicas (36%). En la fase Pos disminuyeron un 37% los ingresos del grupo A.Conclusiones: La HaDQ se reorganizó por la pandemia para atender a más pacientes quirúr-gicos, siendo un recurso asistencial esencial, especialmente durante el confinamiento. (AU)

Introduction: The HaDQ is an alternative to conventional hospitalization for clinically stable surgical patients who require complex nursing procedures due to intensity, frequency or char-acteristics, and control by a surgical specialist at home.Method: Cross-sectional, descriptive and ret-rospective study of the HADQ activity of our hospital during the first six months of 2020, to analyze the impact of the SARSCov2 pandemic in the unit. Three periods are distinguished: pre-pandemic (Jan-Feb), lockdown (Mar-Apr), post-lockdown (May-Jun). Two groups are differen-tiated: A (conventional HaD) and B (COVID19 preoperative screening). Various variables were collected: month, type, stay (HaD and hospi-tal), procedures, readmissions, address, type of visits, covid+. A quantitative and qualitative descriptive statistical analysis of the results ob-tained was carried out.Results: 345 patients were admitted, 225 in group A (phase Pre (34%), Phase C (40%), and phase Post (25%)), and 120 in group B (Phase C (75%), phase Post (25%)). %)). The confinement (phase C) was the most active period of the HADQ, both due to the number of admissions (53%), and the complexity of group A, which re-quired more procedures (71%) and more home visits (52%). There was also an increase in pa-tients from the non-coverage area (42%), which involved medical and nursing visits at the Day Hospital (HD) (21%), and an increase in medi-cal telephone consultations (36%). In the phase Post, the income of group A decreased by 37%.Conclusions: The HaDQ was reorganized due to the pandemic to care for more surgical pa-tients, being an essential care resource, espe-cially during confinement. (AU)

Platelet miRNA Biosignature Discriminates between Dementia with Lewy Bodies and Alzheimer's Disease.

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer's disease (AD), and presents pathological and clinical overlap with both AD and Parkinson's disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD.

Lower Locus Coeruleus MRI intensity in patients with late-life major depression.

BACKGROUND: The locus coeruleus (LC) is the major noradrenergic source in the central nervous system. Structural alterations in the LC contribute to the pathophysiology of different neuropsychiatric disorders, which may increase to a variable extent the likelihood of developing neurodegenerative conditions. The characterization of such alterations may therefore help to predict progression to neurodegenerative disorders. Despite the LC cannot be visualized with conventional magnetic resonance imaging (MRI), specific MRI sequences have been developed to infer its structural integrity. METHODS: We quantified LC signal Contrast Ratios (LCCRs) in late-life major depressive disorder (MDD) (n = 37, 9 with comorbid aMCI), amnestic Mild Cognitive Impairment (aMCI) (n = 21, without comorbid MDD), and healthy controls (HCs) (n = 31), and also assessed the putative modulatory effects of comorbidities and other clinical variables. RESULTS: LCCRs were lower in MDD compared to aMCI and HCs. While no effects of aMCI comorbidity were observed, lower LCCRs were specifically observed in patients taking serotonin/norepinephrine reuptake inhibitors (SNRIs). CONCLUSION: Our results do not support the hypothesis that lower LCCRs characterize the different clinical groups that may eventually develop a neurodegenerative disorder. Conversely, our results were specifically observed in patients with late-life MDD taking SNRIs. Further research with larger samples is warranted to ascertain whether medication or particular clinical features of patients taking SNRIs are associated with changes in LC neurons.

Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson's Disease.

Lewy body diseases (LBD) including dementia with Lewy bodies (DLB) and Parkinson disease (PD) are characterized by alpha-synuclein pathology. DLB is difficult to diagnose and peripheral biomarkers are urgently needed. Therefore, we analyzed the expression of five alpha-synuclein gene (SNCA) transcripts, SNCAtv1, SNCAtv2, SNCAtv3, SNCA126, and SNCA112, in 45 LBD and control temporal cortex samples and in the blood of 72 DLB, 59 PD, and 54 control subjects. The results revealed overexpression of SNCAtv1 and SNCA112 in DLB, and SNCAtv2 in PD temporal cortices. In DLB blood, diminution of all SNCA transcripts was observed. SNCAtv1 and SNCAtv2 were diminished in PD with disease onset before 70 years. SNCAtv3, driven by its own promoter, showed opposite expression in early DLB and PD, suggesting that its amount may be an early, DLB specific biomarker. Correlation between blood transcript levels and disease duration was positive in DLB and negative in PD, possibly reflecting differences in brain alpha-synuclein aggregation rates associated with differences in disease courses. In conclusion, SNCA transcripts showed a disease-specific increase in the brain and were diminished in blood of LBD patients. SNCAtv3 expression was decreased in early DLB and increased in early PD and could be a biomarker for early DLB diagnosis.

Errorless Learning Therapy in Semantic Variant of Primary Progressive Aphasia.

BACKGROUND: The semantic variant of primary progressive aphasia (svPPA) is characterized by a progressive loss of semantic knowledge impairing the ability to name and to recognize the meaning of words. OBJECTIVE: We aimed to evaluate the immediate and short-term effect of errorless learning speech therapy on the naming and recognition of commonly used words in patients with svPPA. METHODS: Eight participants diagnosed with svPPA received 16 sessions of intensive errorless learning speech therapy. Naming and word comprehension tasks were evaluated at baseline, immediately postintervention, and at follow-up after 1, 3, and 6 months. These evaluations were performed using two item sets (a trained list and an untrained list). RESULTS: In the naming tasks, patients showed a significant improvement in trained items immediately after the intervention, but that improvement decayed progressively when therapy ended. No improvements were found either in trained comprehension or in untrained tasks. CONCLUSION: Errorless learning therapy could improve naming ability in patients with svPPA. This effect may be due to the relative preservation of episodic memory, but the benefit is not maintained over time, presumably because there is no consolidation.

Active bilingualism delays the onset of mild cognitive impairment.

Lifelong bilingualism may contribute to cognitive reserve (CR) in neurodegenerative diseases as shown by a delay of the age at symptom onset in bilinguals with Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). However, some studies have failed to show this bilingual advantage, suggesting that it might depend on the type and degree of bilingualism. In the present study, we tested the hypothesis that active bilingualism, defined as the continuous use of the two languages as opposed to second language exposition only, may protect against cognitive decline. Moreover, we investigated whether bilingualism as a CR factor may be explained by an advantage within the executive control (EC) system. To do so, we collected clinical measures (age at onset of cognitive symptoms, age at the first medical visit for cognitive impairments, and age at diagnosis) in patients with MCI and patients with AD with different degrees of language experience and usage of Catalan and Spanish. Additionally, all participants were tested on four EC tasks and one long-term memory recognition task. First, results from multiple regression analyses showed that active bilingualism was a significant predictor of delay in the age at onset for all the clinical measures in MCI, but not AD patients. Second, the effect of active bilingualism was independent of occupation, educational level and job attainment across the individuals' lifespan. Finally, although we did not find an effect of active bilingualism across all EC tasks, we did find an effect for conflict resolution. These results are discussed in the context of CR hypotheses, suggesting that compensatory mechanisms may play a role in protecting against cognitive decline.

Exploratory study on microRNA profiles from plasma-derived extracellular vesicles in Alzheimer's disease and dementia with Lewy bodies.

BACKGROUND: Because of the increasing life expectancy in our society, aging-related neurodegenerative disorders are one of the main issues in global health. Most of these diseases are characterized by the deposition of misfolded proteins and a progressive cognitive decline. Among these diseases, Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common types of degenerative dementia. Although both show specific features, an important neuropathological and clinical overlap between them hampers their correct diagnosis. In this work, we identified molecular biomarkers aiming to improve the misdiagnosis between both diseases. METHODS: Plasma extracellular vesicles (EVs) -from DLB, AD and healthy controls- were isolated using size-exclusion chromatography (SEC) and characterized by flow cytometry, Nanoparticle Tracking Analysis (NTA) and cryo-electron microscopy. Next Generation Sequencing (NGS) and related bibliographic search was performed and a selected group of EV-associated microRNAs (miRNAs) was analysed by qPCR. RESULTS: Results uncovered two miRNAs (hsa-miR-451a and hsa-miR-21-5p) significantly down-regulated in AD samples respect to DLB patients, and a set of four miRNAs (hsa-miR-23a-3p, hsa-miR-126-3p, hsa-let-7i-5p, and hsa-miR-151a-3p) significantly decreased in AD respect to controls. The two miRNAs showing decreased expression in AD in comparison to DLB provided area under the curve (AUC) values of 0.9 in ROC curve analysis, thus suggesting their possible use as biomarkers to discriminate between both diseases. Target gene analysis of these miRNAs using prediction online tools showed accumulation of phosphorylation enzymes, presence of proteasome-related proteins and genes involved in cell death among others. CONCLUSION: Our data suggest that plasma-EV associated miRNAs may reflect a differential profile for a given dementia-related disorder which, once validated in larger cohorts of patients, could help to improve the differential diagnosis of DLB versus AD.

A unique common ancestor introduced P301L mutation in MAPT gene in frontotemporal dementia patients from Barcelona (Baix Llobregat, Spain).

The County of Baix Llobregat (Barcelona, Catalonia, Spain) presents a high prevalence of familial frontotemporal dementia (FTD) in the presence of P301L mutation in the MAPT gene. To evaluate a possible unique founder effect of P301L, and its age, the analysis of 20 single-nucleotide polymorphisms covering 50 kb and 12 single-nucleotide polymorphisms located along 30 Mb around the mutation was performed by developing 2 multiplex single-base extension reactions. In addition, families with affected and healthy individuals from France and Italy were analyzed. The FTD-affected individuals from Barcelona carried the same 50-kb haplotype linked to P301L mutation, suggesting a unique common ancestor, as opposed to French patients. Italian patients are also probably descendants of a unique ancestor, which would be different from that of Barcelona. Diversity of 30-Mb haplotypes found in Barcelona and the inference of the mutation age in these populations, among other reasons, suggest that prevalence of FTD linked to P301L MAPT mutation is the result of a locally originated mutation.

Comprehensive proteomic profiling of plasma-derived Extracellular Vesicles from dementia with Lewy Bodies patients.

Proteins and nucleic acids contained in extracellular vesicles (EVs) are considered a feasible source of putative biomarkers for physiological and pathological conditions. Within the nervous system, not only neurons but also other brain cells are able to produce EVs, which have been involved in their physiological processes and also in the development and course of several neurodegenerative diseases. Among these, dementia with Lewy bodies (DLB) is the second cause of dementia worldwide, though most cases are missed or misdiagnosed as Alzheimer's disease (AD) due to the important clinical and pathological overlap between both diseases. In an attempt to find reliable biomarkers for DLB diagnosis, our group characterized the proteome of plasma-derived EVs from DLB patients compared to aged-matched healthy controls (HCs) using two different proteomic LC-MS/MS approaches. Remarkably, we found that gelsolin and butyrylcholinesterase were differentially identified between DLB and HCs. Further validation of these results using conventional ELISA techniques, and including an additional group of AD patients, pointed to decreased levels of gelsolin in plasma-EVs from DLB compared to HCs and to AD samples. Thus, gelsolin may be considered a possible biomarker for the differentiation between DLB and AD.

[Preliminary multicentric study on the nutritional status in hospitalization at home (HaD) with the same informational application of nutritional assessment]. / Estudio multicéntrico preliminar sobre el estado nutricional en hospitalización a domicilio (HaD) con una misma aplicación informática de valoración nutricional.

INTRODUCTION: the prevalence of hospital malnutrition is high and involves an increase in health care costs. Home hospitalization (HH) allows better clinically stable patient control after an acute illness by a highly specialized health care team. OBJECTIVE: to know the nutritional condition of home hospitalization patients using a computer application that allows the implementation of early nutritional measures at home and improves post-hospital control of these patients. MATERIAL AND METHODS: prospective multicenter study of the nutritional condition of patients in four different home hospitalization centers during a period of two consecutive months in 2016. Variables were collected: home hospitalization, age, gender, reason for admission, associated morbidity, origin, diagnosis, social assessment, previous nutritional support, height, weight, weight loss, time of weight loss, total proteins, albumin, lymphocytes, cholesterol, body mass index (BMI), nutritional condition, type and degree of malnutrition. Nutritional condition was assessed using the application HEN-Persan and results were statistically analyzed using the SPSS 21.0 software. RESULTS: no significant differences were found between the four centers. In home hospitalization patients, 36% presented a normal nutritional screening and 87% presented some degree of malnutrition, while combined malnutrition prevailed (63%). Depending on the nutritional degree, 36% of patients had mild malnutrition, 27% presented moderate malnutrition and 35% had severe malnutrition. CONCLUSIONS: a computer application allows for an immediate, secure and reliable nutritional assessment in home hospitalization that helps introduce early nutritional measures and improve post-hospital control of patients.

INTRODUCCIÓN: la malnutrición hospitalaria tiene una elevada prevalencia y comporta un incremento del coste sanitario. La hospitalización a domicilio (HaD) permite el control en el domicilio de un episodio hospitalario agudo estable clínicamente por un equipo sanitario especializado.Objetivo: conocer el estado nutricional de los pacientes que ingresen en HaD con una misma aplicación informática (app) para poder instaurar medidas nutricionales precoces en el domicilio y mejorar la evolución posthospitalaria de los pacientes. MATERIAL Y METODOLOGÍA: estudio multicéntrico prospectivo y descriptivo del estado nutricional en cuatro unidades de HaD, durante un periodo de dos meses consecutivos durante el año 2016. Se recogieron las variables: unidad de HaD, edad, sexo, motivo de ingreso, patología asociada, procedencia, diagnóstico, valoración social, soporte nutricional previo, talla, peso, pérdida de peso, tiempo de la pérdida de peso, proteínas totales, albúmina, linfocitos, colesterol, índice de masa corporal (IMC), estado nutricional según el IMC, riesgo nutricional, tipo y grado de desnutrición. Se realizó la valoración nutricional con la app HEN-Persan y se analizaron los resultados estadísticamente con el programa informático SPSS 21.0. RESULTADOS: no existen diferencias significativas entre las cuatro unidades. Globalmente, el 36% de pacientes ingresados en HaD presentaban un estado nutricional normal. El 87% presentaba algún tipo de malnutrición, predominando la desnutrición de tipo mixta (63%). Según el grado,fue leve (36%), moderada (27%) y grave (35%). CONCLUSIONES: la utilización de una app permite tener una valoración nutricional inmediata, de manera fácil, segura y fiable en HaD, para poder introducir medidas nutricionales precoces y mejorar la evolución posthospitalaria de los pacientes.

Estudio multicéntrico preliminar sobre el estado nutricional en hospitalización a domicilio (HaD) con una misma aplicación informática de valoración nutricional / Preliminary multicentric study on the nutritional status in hospitalization at home (HaD) with the same informational application of nutritional assessment

Introducción: la malnutrición hospitalaria tiene una elevada prevalencia y comporta un incremento del coste sanitario. La hospitalización a domicilio (HaD) permite el control en el domicilio de un episodio hospitalario agudo estable clínicamente por un equipo sanitario especializado. Objetivo: conocer el estado nutricional de los pacientes que ingresen en HaD con una misma aplicación informática (app) para poder instaurar medidas nutricionales precoces en el domicilio y mejorar la evolución posthospitalaria de los pacientes. Material y metodología: estudio multicéntrico prospectivo y descriptivo del estado nutricional en cuatro unidades de HaD, durante un periodo de dos meses consecutivos durante el año 2016. Se recogieron las variables: unidad de HaD, edad, sexo, motivo de ingreso, patología asociada, procedencia, diagnóstico, valoración social, soporte nutricional previo, talla, peso, pérdida de peso, tiempo de la pérdida de peso, proteínas totales, albúmina, linfocitos, colesterol, índice de masa corporal (IMC), estado nutricional según el IMC, riesgo nutricional, tipo y grado de desnutrición. Se realizó la valoración nutricional con la app HEN-Persan y se analizaron los resultados estadísticamente con el programa informático SPSS 21.0. Resultados: no existen diferencias significativas entre las cuatro unidades. Globalmente, el 36% de pacientes ingresados en HaD presentaban un estado nutricional normal. El 87% presentaba algún tipo de malnutrición, predominando la desnutrición de tipo mixta (63%). Según el grado, fue leve (36%), moderada (27%) y grave (35%). Conclusiones: la utilización de una app permite tener una valoración nutricional inmediata, de manera fácil, segura y fiable en HaD, para poder introducir medidas nutricionales precoces y mejorar la evolución posthospitalaria de los pacientes

Introduction: the prevalence of hospital malnutrition is high and involves an increase in health care costs. Home hospitalization (HH) allows better clinically stable patient control after an acute illness by a highly specialized health care team. Objective: to know the nutritional condition of home hospitalization patients using a computer application that allows the implementation of early nutritional measures at home and improves post-hospital control of these patients. Material and methods: prospective multicenter study of the nutritional condition of patients in four different home hospitalization centers during a period of two consecutive months in 2016. Variables were collected: home hospitalization, age, gender, reason for admission, associated morbidity, origin, diagnosis, social assessment, previous nutritional support, height, weight, weight loss, time of weight loss, total proteins, albumin, lymphocytes, cholesterol, body mass index (BMI), nutritional condition, type and degree of malnutrition. Nutritional condition was assessed using the application HEN-Persan and results were statistically analyzed using the SPSS 21.0 software. Results: no significant differences were found between the four centers. In home hospitalization patients, 36% presented a normal nutritional screening and 87% presented some degree of malnutrition, while combined malnutrition prevailed (63%). Depending on the nutritional degree, 36% of patients had mild malnutrition, 27% presented moderate malnutrition and 35% had severe malnutrition. Conclusions: a computer application allows for an immediate, secure and reliable nutritional assessment in home hospitalization that helps introduce early nutritional measures and improve post-hospital control of patients

Glucocerebrosidase mRNA is Diminished in Brain of Lewy Body Diseases and Changes with Disease Progression in Blood.

Parkinson disease (PD) and dementia with Lewy bodies (DLB) are Lewy body diseases characterized by abnormal alpha-synuclein deposits and overlapping pathological features in the brain. Several studies have shown that glucocerebrosidase (GBA) deficiency is involved in the development of LB diseases. Here, we aimed to find out if this deficiency starts at the transcriptional level, also involves alternative splicing, and if GBA expression changes in brain are also detectable in blood of patients with LB diseases. The expression of three GBA transcript variants (GBAtv1, GBAtv2 and GBAtv5) was analyzed in samples from 20 DLB, 25 PD and 17 control brains and in blood of 20 DLB, 26 PD patients and 17 unaffected individuals. Relative mRNA expression was determined by real-time PCR. Expression changes were evaluated by the ΔΔCt method. In brain, specific expression profiles were identified in the temporal cortex of DLB and in the caudate nucleus of PD. In blood, significant GBA mRNA diminution was found in both DLB and PD patients. Early PD and early-onset DLB patients showed lowest GBA levels which were normal in PD patients with advanced disease and DLB patients who developed disease after 70 years of age. In conclusion, disease group specific GBA expression profiles were found in mostly affected areas of LBD. In blood, GBA expression was diminished in LB diseases, especially in patients with early onset DLB and in patients with early PD. Age of disease onset exerts an opposite effect on GBA expression in DLB and PD.

Frontotemporal Dementia Caused by the P301L Mutation in the MAPT Gene: Clinicopathological Features of 13 Cases from the Same Geographical Origin in Barcelona, Spain.

BACKGROUND/AIMS: We identified and studied 13 patients carrying the P301L mutation in the MAPT gene from the same area (Baix Llobregat County) in Barcelona, Spain. METHODS: The demographic and clinical features were reviewed retrospectively. Detailed neuropathological characterization was obtained in 9 subjects. To investigate the origin of the P301L mutation in these families, 20 single nucleotide polymorphisms (SNPs) in the MAPT gene were analyzed. RESULTS: The mean age at disease onset was 51 years and the mean disease duration was 7 years. The most common initial symptoms were behavioral changes (54%), followed by language disturbances (31%) and memory loss (15%). 46% developed parkinsonism. Neuropathology showed an extensive neuronal and glial 4-repeat (4R) tauopathy with "mini-Pick"-like bodies in the dentate gyrus as the characteristic underlying pathology in all cases. In 1 subject, additional 4R globular glial inclusions were observed. All the mutation carriers showed the same haplotype for the SNPs analyzed, suggesting a common ancestor. CONCLUSION: These findings suggest a relative homogeneous clinicopathological phenotype in P301L MAPT mutation carriers in our series. This phenotype might help in the differential diagnosis from other tauopathies and be a morphological hint for genetic testing. The haplotype analysis results suggest a founder effect of the P301L mutation in this area.

GBA Mutations Are Associated With Earlier Onset and Male Sex in Dementia With Lewy Bodies.

BACKGROUND: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are Lewy body diseases characterized by similar pathological features. Several studies have shown a relation between alterations in the glucocerebrosidase gene (GBA) and the development of LB diseases. Here, we explored the role of GBA mutations in Spanish DLB patients. METHODS: GBA mRNA sequences were analyzed in a neuropathological (50 DLB, 43 PD, and 34 control brains) and in a clinical cohort (47 DLB patients and 131 unaffected individuals). RESULTS: Sixteen GBA mutation carriers were identified, 5 of which were brains with pure DLB. The most common mutation, E326K, was strongly associated with pure DLB and PD with dementia. GBA mutations were overrepresented in men and associated with earlier DLB onset. CONCLUSIONS: GBA mutations are also an important risk factor for DLB development in the Spanish population, are associated with earlier disease onset, and are more prevalent in men. © 2015 International Parkinson and Movement Disorder Society.

Cognitive impairment in ALS patients and validation of the Spanish version of the ALS-CBS test.

Our aim was to develop and validate the Spanish version of the Amyotrophic Lateral Sclerosis Cognitive Behavioural Screen (ALS-CBS) and investigate behavioural/cognitive impairment in our ALS patients. We enrolled 50 patients with definite or probable ALS, evaluated by the Motor Neuron Disease Unit (using El Escorial criteria) and Dementia Unit, and assessed with the Spanish ALS-CBS. The patients' cognitive/behavioural status was classified according to current criteria. Patients were classified into each diagnostic category: ALS-no impairment, 36%; ALS-mild cognitive impairment, 34%; ALS-mild behavioural impairment, 6%; ALS-mild cognitive/behavioural impairment, 12%; ALS-frontotemporal dementia, 12%. Cognitive impairment was more common in bulbar (90.9%) than spinal (48.7%) forms (p < 0.012). The Spanish ALS-CBS was validated. Performance to differentiate normal vs. impaired individuals was: 1) cognition (cut-off 15; AUC, 84.7%): sensitivity 86.2%, specificity 62%, positive predictive value 75.8%, negative predictive value 76.5%; 2) behaviour (cut-off 36; AUC, 83.3%): sensitivity 93.3%, specificity 74.3%, positive predictive value 61%, negative predictive value 96.3%. Performance to differentiate between patients with and without dementia: 1) cognition (cut-off 8; AUC, 87.3%): sensitivity 83.3%, specificity 75%, positive predictive value 31.3%, negative predictive value 97.1%; 2) behaviour (cut-off 35; AUC, 80.9%): sensitivity 83.3%, specificity 69%, positive predictive value 25%, negative predictive value 96.7%. In conclusion, cognitive impairment is common in ALS patients, particularly in bulbar forms. The Spanish version of the ALS-CBS is useful for screening cognitive/behavioural impairment in this population.

Severe hyperammonemia in late-onset ornithine transcarbamylase deficiency triggered by steroid administration.

Ornithine transcarbamylase deficiency (OTCD) is a rare X-linked disorder of urea synthesis leading to hyperammonemia. Several late-onset cases have been reported. Undiagnosed and untreated patients are at the risk of death or suffering from irreversible sequelae. We describe a 56-year-old patient who presented with acute encephalopathy after steroid treatment. Hyperammonemia due to OTCD was diagnosed and a mutation was found. This allowed us to diagnose two other family members with unexplained encephalopathy who are now asymptomatic on a low-protein diet. OTCD should be considered in any patient with hyperammonemic encephalopathy and immediate treatment should be given to avoid a fatal outcome. We emphasize the need to examine other family members if the diagnosis is confirmed, in order to prevent further life-threatening episodes of encephalopathy or neonatal coma of newborn.

Demencia y diabetes: ¿relación casual o causal? / Dementia and diabetes: Casual or causal relationship?

Diversos estudios han mostrado la existencia de una asociación epidemiológica entre la diabetes mellitus (DM) y la demencia. Aunque esta asociación es más evidente para la demencia vascular, también se ha descrito entre DM y enfermedad de Alzheimer (EA). En esta revisión se evalúan las diversas hipótesis que pueden explicar la asociación entre DM y demencia. La hiperglucemia aguda, la microangiopatía como consecuencia de la hiperglucemia crónica, la hipoglucemia y la resistencia a la insulina son mecanismos potencialmente implicados en la relación entre diabetes y deterioro cognitivo. Respecto a la última, se ha propuesto el término de diabetes 3 como la situación que se da cuando la hiperinsulinemia en respuesta a la resistencia a la insulina comporta una disminución de la insulina efectiva cerebral, conllevando una mala regulación de la enzima degradante de la insulina y una acumulación de beta-amiloide. Así pues, la EA podría estar condicionada, al menos en parte, por una resistencia cerebral a la insulina. Existen diversos estudios que aportan el concepto de que un mejor control metabólico, especialmente en edades no muy avanzadas de la vida, comporta un mayor rendimiento cognitivo. No existe una clara evidencia de si el uso de alguna familia farmacológica en concreto para el tratamiento de la DM es mejor que otra. Es importante que los médicos responsables del control metabólico de los pacientes con DM conozcan su posible asociación con la demencia e incorporen la exploración de la cognición en las visitas de control de los pacientes con DM (AU)

Several studies have reported the existence of an epidemiological association between diabetes mellitus (DM) and dementia. Although this association is more evident for vascular dementia, it is also described in Alzheimer's disease (AD). In this review we evaluate the different hypotheses that may explain the association between DM and dementia. We can consider the existence of a diabetes type 3 as the situation that occurs when hyperinsulinemia in response to insulin resistance leads to a decrease of the brain insulin and a poor regulation of insulin-degrading enzyme; thus, beta-amyloid accumulates, among other mechanisms, by the decline of its degradation by insulin-degrading enzyme. Consequently, AD may be related, at least in part, to a brain insulin resistance. There are several studies that prove the concept that a better metabolic control, especially in not very old people, is associated with an increased cognitive performance. It is not known whether the use of any specific drug for the treatment of DM is better than any other. It is important for physicians responsible for the metabolic control of diabetic patients to know this possible association, and to explore cognition in the control visits of patients with DM (AU)

[Dementia and diabetes: casual or causal relationship?]. / Demencia y diabetes: ¿relación casual o causal?

Several studies have reported the existence of an epidemiological association between diabetes mellitus (DM) and dementia. Although this association is more evident for vascular dementia, it is also described in Alzheimer's disease (AD). In this review we evaluate the different hypotheses that may explain the association between DM and dementia. We can consider the existence of a diabetes type 3 as the situation that occurs when hyperinsulinemia in response to insulin resistance leads to a decrease of the brain insulin and a poor regulation of insulin-degrading enzyme; thus, beta-amyloid accumulates, among other mechanisms, by the decline of its degradation by insulin-degrading enzyme. Consequently, AD may be related, at least in part, to a brain insulin resistance. There are several studies that prove the concept that a better metabolic control, especially in not very old people, is associated with an increased cognitive performance. It is not known whether the use of any specific drug for the treatment of DM is better than any other. It is important for physicians responsible for the metabolic control of diabetic patients to know this possible association, and to explore cognition in the control visits of patients with DM.

Prevalence of altered passive eruption in orthodontically treated and untreated patients.

BACKGROUND: Some authors have reported that after orthodontic treatment (OT), a "gummy smile" might develop. Nevertheless, there are no studies in the literature that investigate whether OT increases the presence of altered passive eruption (APE). The primary aim of this cross-sectional study is to evaluate the prevalence of APE after OT (OT group) and compare it with patients who never received OT (control group). A secondary aim is to identify which variables are related to APE. METHODS: The study population consisted of 190 patients (95 patients each in the control and OT groups), providing 1,140 anterior teeth for the clinical examination. The following clinical parameters were assessed: presence or absence of APE, clinical crown length, and gingival biotype, which was divided into three categories: thin-scalloped, thick-flat, and thick-scalloped. RESULTS: Twenty-eight patients (29.5%) were diagnosed with APE in the control group and 40 (42.1%) in the OT group, although this difference was not statistically significant (P = 0.07). Furthermore, 34 (75.6%) patients with thick-flat biotype were diagnosed with APE, whereas 30 (31.3%) and four (8.2%) with thick-scalloped and thin-scalloped biotypes, respectively, had APE. These differences were statistically significant (P <0.001). CONCLUSIONS: It was concluded that: 1) the prevalence of APE is higher after OT but not to a statistically significant degree and 2) APE is more common in individuals with a thick-flat gingival biotype.