Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimer's disease.

Autosomal dominant Alzheimer's disease (ADAD) is genetically determined, but variability in age of symptom onset suggests additional factors may influence cognitive trajectories. Although apolipoprotein E (APOE) genotype and educational attainment both influence dementia onset in sporadic AD, evidence for these effects in ADAD is limited. To investigate the effects of APOE and educational attainment on age-related cognitive trajectories in ADAD, we analyzed data from 675 Presenilin-1 E280A mutation carriers and 594 non-carriers. Here we show that age-related cognitive decline is accelerated in ADAD mutation carriers who also have an APOE e4 allele compared to those who do not and delayed in mutation carriers who also have an APOE e2 allele compared to those who do not. Educational attainment is protective and moderates the effect of APOE on cognition. Despite ADAD mutation carriers being genetically determined to develop dementia, age-related cognitive decline may be influenced by other genetic and environmental factors.

Evaluación del Miedo a la Recurrencia del cáncer en español: el Cuestionario de Miedo a la Recurrencia del Cáncer y Escala General del Miedo a la Recurrencia del Cáncer: un estudio piloto / Assessment of fear of cancer recurrence in Spanish: Fear of Recurrence Questionnaire and he General Scale of Fear of Cancer Recurrence: A pilot study

El objetivo de este estudio es la elaboración de un cuestionario de evaluación del miedo a la recurrencia del cáncer en español. Método: se presenta un estudio piloto de diseño correlacional trasversal elaborado en dos fases: 1) creación del cuestionario del miedo a la recurrencia del cáncer (CMRC) y de la Escala General del Miedo a la Recurrencia del Cáncer (EGMRC); 2) evaluación de sus propiedades psicométricas. Resultados: para la elaboración de los cuestionarios se utilizó el acuerdo entre expertos medido por la V de Aiken. El CMRC queda finalmente configurado con 8 ítems que se responden con una escala tipo Likert de 0-4 y un Alfa de Cronbach de 0,85. La EGMRC de una sola pregunta que se responde con una escala de 0-100 correlaciona hasta un 0,84 con el CMRC. Se utilizó una muestra de 50 mujeres supervivientes de cáncer ginecológico seleccionadas en el Hospital Universitario Clínico San Carlos de Madrid. Ambas escalas correlacionan con el nivel de ansiedad de las pacientes y la función emocional de calidad de vida. No se hallan correlaciones con los niveles de depresión. Conclusiones: El CMRC y la EGMRC son dos instrumentos que pueden ser válidos para la evaluación del miedo a la recurrencia del cáncer en pacientes supervivientes de cáncer ginecológico (AU)

The objective of this study is the elaboration of a questionnaire for the evaluation of the fear of recurrence of cancer in Spanish. Method: A pilot study with a cross-sectional correlational design is presented, elaborated in two phases: 1) creation of the Fear Cancer recurrence Questionnaire (CMRC) and the General Scale of Fear of Cancer Recurrence (EGMRC); 2) evaluation of their psychometric properties. Results: for the elaboration of the questionnaires, the agreement between experts was used, measured by Aiken’s V. The CMRC questionnaire is finally configured with 8 items that are answered with a Likert-type scale of 0-4 and a Cronbach’s Alpha of 0.851. The EGMRC consists of a single question that is answered with a scale of 0-100 correlates up to 0.84 with the CMRC. A sample of 50 female survivors of gynecological cancer selected from the Hospital Universitario Clínico San Carlos in Madrid was used. Both scales correlate with the level of anxiety of the patients and the emotional function of quality of life. No correlations with levels of depression were found. Conclusions: The CMRC and the EGMRC are two instruments that may be valid for the evaluation of FCR in Spanish for survivors of gynecological cancer (AU)

Associations between plasma neurofilament light, in vivo brain pathology, and cognition in non-demented individuals with autosomal-dominant Alzheimer's disease.

BACKGROUND: Neurofilament light (NfL) is a promising biomarker of early neurodegeneration in Alzheimer's disease (AD). We examined whether plasma NfL was associated with in vivo amyloid beta and tau, and cognitive performance in non-demented presenilin-1 (PSEN1) E280A mutation carriers. METHODS: Twenty-five mutation carriers and 19 non-carriers (age range: 28 to 49 years) were included in this study. Participants underwent 11C Pittsburgh compound B (PiB)-PET (positron emission tomography), flortaucipir-PET, blood sampling, and cognitive testing. RESULTS: Mutation carriers exhibited higher plasma NfL levels than non-carriers. In carriers, higher NfL levels were related to greater regional tau burden and worse cognition, but not amyloid beta load. When we adjusted for age, a proxy of disease progression, elevated plasma NfL levels were only correlated with worse memory recall. CONCLUSIONS: Findings support an association between plasma NfL, cognition, and tau pathology in non-demented individuals at genetic risk for developing AD dementia. Plasma NfL may be useful for selecting individuals at increased risk and tracking disease progression in AD.

The INECO Frontal Screening for the Evaluation of Executive Dysfunction in Cerebral Small Vessel Disease: Evidence from Quantitative MRI in a CADASIL Cohort from Colombia.

OBJECTIVES: Executive dysfunction is a predominant cognitive symptom in cerebral small vessel disease (SVD). The Institute of Cognitive Neurology Frontal Screening (IFS) is a well-validated screening tool allowing the rapid assessment of multiple components of executive function in Spanish-speaking individuals. In this study, we examined performance on the IFS in subjects with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an inherited condition leading to the early onset of SVD. We further explored associations between performance on the IFS and magnetic resonance imaging (MRI) markers of SVD. METHODS: We recruited 24 asymptomatic CADASIL subjects and 23 noncarriers from Colombia. All subjects underwent a research MRI and a neuropsychological evaluation, including the IFS. Structural MRI markers of SVD were quantified in each subject, together with an SVD Sum Score representing the overall burden of cerebrovascular alterations. General linear model, correlation, and receiver operating characteristic curve analyses were used to explore group differences on the IFS and relationships with MRI markers of SVD. RESULTS: CADASIL subjects had a significantly reduced performance on the IFS Total Score. Performance on the IFS correlated with all quantified markers of SVD, except for brain atrophy and perivascular spaces enlargement. Finally, while the IFS Total Score was not able to accurately discriminate between carriers and noncarriers, it showed adequate sensitivity and specificity in detecting the presence of multiple MRI markers of SVD. CONCLUSIONS: These results suggest that the IFS may be a useful screening tool to assess executive function and disease severity in the context of SVD.

Determinación de anticuerpos anti beta 2 glicoproteina I en pacientes con síndrome antifosfolípido / Anti- ß2 glycoprotein antibodies in patients with antiphospholipid syndrome

El objetivo de este estudio fue comparar la presencia de anticuerpos anti-B2glicoproteína I (anti-B2GPI) con las pruebas convencionales de laboratorio de anticuerpos anticardiolipina (aCL) y anticoagulante lúpico, y con las manifestaciones clínicas del síndrome antifosfolípido (SAF).Se incluyeron en el estudio 80 mujeres con SAF; 35 de ellas de la consulta de Reumatología y las otras 45 con historia de aborto recurrente espontáneo (ARE); 5 mujeres de la consulta de Reumatología sin SAF, 27 mujeres con ARE, sin SAF y un grupo control de 20 mujeres sanas en edad reproductiva. Se investigaron la presencia de anticuerpos IgG e IgM anticardiolipina (aCL) e IgG anti-B2GPI por la técnica de ELISA, y el anticoagulante lúpico por la determinación del tiempo parcial de tromboplastina activado. Adicionalmente, se registraron las manifestaciones clínicas asociadas al SAF.De las pacientes con SAF, 25.7 por ciento del grupo de Reumatología (9/35) y 4.4 por ciento de las pacientes con ARE (2/45) fueron positivas para anticuerpos anti-?2GPI, mientras que ninguna de las mujeres sin SAF, ni de las mujeres del grupo control, fue positiva. La asociación entre la presencia de anti-B2GPI y los anticuerpos IgG e IgM aCL mostró una diferencia significativa en los títulos de 3+ (altamente positivos) en contraste con los individuos negativos para anti-B2GPI. La positividad del anticoagulante lúpico también se correlacionó con la presencia de anticuerpos anti-B2GPI. No hubo diferencia significativa entre las diversas manifestaciones clínicas del SAF y la presencia de dichos anticuerpos.En conclusión, la determinación de anticuerpos anti-B2GPI tiene una alta especificidad en pacientes con SAF pero no se asoció con ninguna manifestación clínica en particular.

El objetivo de este estudio fue comparar la presencia de anticuerpos anti- ß2glicoproteína I (anti-ß2GPI) con las pruebas convencionales de laboratorio de anticuerpos anticardiolipina (aCL) y anticoagulante lúpico, y con las manifestaciones clínicas del síndrome antifosfolípido (SAF). Se incluyeron en el estudio 80 mujeres con SAF; 35 de ellas de la consulta de Reumatología y las otras 45 con historia de aborto recurrente espontáneo (ARE); 5 mujeres de la consulta de Reumatología sin SAF, 27 mujeres con ARE, sin SAF y un grupo control de 20 mujeres sanas en edad reproductiva. Se investigaron la presencia de anticuerpos IgG e IgM anticardiolipina (aCL) e IgG anti-ß2GPI por la técnica de ELISA, y el anticoagulante lúpico por la determinación del tiempo parcial de tromboplastina activado. Adicionalmente, se registraron las manifestaciones clínicas asociadas al SAF. De las pacientes con SAF, 25.7% del grupo de Reumatología (9/35) y 4.4% de las pacientes con ARE (2/45) fueron positivas para anticuerpos anti- ß2GPI, mientras que ninguna de las mujeres sin SAF, ni de las mujeres del grupo control, fue positiva. La asociación entre la presencia de anti-ß2GPI y los anticuerpos IgG e IgM aCL mostró una diferencia significativa en los títulos de 3+ (altamente positivos) en contraste con los individuos negativos para anti-ß2GPI. La positividad del anticoagulante lúpico también se correlacionó con la presencia de anticuerpos anti-ß2GPI. No hubo diferencia significativa entre las diversas manifestaciones clínicas del SAF y la presencia de dichos anticuerpos. En conclusión, la determinación de anticuerpos anti-ß2GPI tiene una alta especificidad en pacientes con SAF pero no se asoció con ninguna manifestación clínica en particular

Autosomal recessive juvenile parkinsonism Cys212Tyr mutation in parkin renders lymphocytes susceptible to dopamine- and iron-mediated apoptosis.

Mutations in parkin are implicated in the pathogenesis of autosomal recessive juvenile parkinsonism (AR-JP) disease. We show that homozygote Cys212Tyr parkin mutation in AR-JP patients renders lymphocytes sensitive to dopamine, iron and hydrogen peroxide stimuli. Indeed, dopamine-induced apoptosis by four alternative mechanisms converging on caspase-3 activation and apoptotic morphology: (1) NF-kappaB-dependent pathway; mitochondrial dysfunction either by (2) H(2)O(2) or (3) hydroxyl exposure and (4) increase of unfolded-protein stress. We also demonstrate that 17beta-estradiol and testosterone prevent homozygote lymphocytes from oxidative stressors-evoked apoptosis. These results may contribute to understanding the relationship between genetic and environmental factors and iron in AR-JP.

Abeta[25-35] peptide and iron promote apoptosis in lymphocytes by an oxidative stress mechanism: involvement of H2O2, caspase-3, NF-kappaB, p53 and c-Jun.

The Abeta deposition in the neuritic plaques is one of the major neuropathological hallmarks of the Alzheimer disease (AD). Studies in vitro have demonstrated that the Abeta[25-35] fragment, which contains the cytotoxic functional sequence of the amyloid peptide, induces neurotoxicity and cell death by apoptosis. Despite intense investigations, a complete picture of the precise molecular cascade leading to cell death in a single cellular model is still lacking. In this study, we provide evidence that Abeta[25-35] induce apoptosis either alone or in presence of iron in peripheral blood lymphocytes cells (PBL) in a concentration-dependent fashion by an oxidative stress mechanism involving: (1) the production of hydrogen peroxide (H2O2), reflected by rhodamine-positive fluorescent cells, (2) activation and/or translocation of NF-kappaB, p53 and c-Jun transcription factors showed by immunocytochemical diaminobenzidine positive nuclei, (3) activation of NF-kappaB complex by electrophoretic mobility shift assay/immuno-blotting/and ammonium pyrrolidinedithiocarbamate (PDTC) inhibition, (4) caspase-3 activation, reflected by caspase Ac-DEVD-cho inhibition, (5) mRNA synthesis de novo according to actinomycin D cell death inhibition. These results are consistent with the notion that the Abeta[25-35]/H2O2 generation precede the apoptotic process and that once H2O2 is generated, it is able to trigger a specific cell death signalisation. Thus, taken together these results, we present a well-ordered cascade of the major molecular events leading PBL to apoptosis. These results may contribute to explain the importance of Abeta alone or in the presence of redox-available iron in association with Abeta plaques (and neurofibrillary tangles) in AD brains and the significant role played by H2O2 as a second messenger of death signal in some degenerative diseases linked to oxidative stress stimuli.

La psicología en CEDECIS como aporte a la psicología social comunitaria / Psychology in CEDECIS as a contribution to community social psychology

El psicólogo de la Corporación CEDECIS es un profesional que posee un método que le permite escuchar, analizar, entender, interpretar e intervenir los procesos Psicológicos de los actores de la comunidad educativa; en ella, se interesa esencialmente por vehiculizar la resignificación de los diferentes intercambios que se dan en las dinámicas internas de la escuela.

The psychologist of the CEDECIS Corporation is a professional who possesses a method that allows him to listen, analyze, understand, interpret and intervene the psychological processes of the actors of the educational community; in it, it is essentially interested in conveying the resignification of the different exchanges that occur in the internal dynamics of the school.