Social cognition impairment in genetic frontotemporal dementia within the GENFI cohort

A key symptom of frontotemporal dementia (FTD) is difficulty interacting socially with others. Social cognition problems in FTD include impaired emotion processing and theory of mind difficulties, and whilst these have been studied extensively in sporadic FTD, few studies have investigated them in familial FTD. Facial Emotion Recognition (FER) and Faux Pas (FP) recognition tests were used to study social cognition within the Genetic Frontotemporal Dementia Initiative (GENFI), a large familial FTD cohort of C9orf72, GRN, and MAPT mutation carriers. 627 participants undertook at least one of the tasks, and were separated into mutation-negative healthy controls, presymptomatic mutation carriers (split into early and late groups) and symptomatic mutation carriers. Groups were compared using a linear regression model with bootstrapping, adjusting for age, sex, education, and for the FP recognition test, language. Neural correlates of social cognition deficits were explored using a voxel-based morphometry (VBM) study. All three of the symptomatic genetic groups were impaired on both tasks with no significant difference between them. However, prior to onset, only the late presymptomatic C9orf72 mutation carriers on the FER test were impaired compared to the control group, with a subanalysis showing differences particularly in fear and sadness. The VBM analysis revealed that impaired social cognition was mainly associated with a left hemisphere predominant network of regions involving particularly the striatum, orbitofrontal cortex and insula, and to a lesser extent the inferomedial temporal lobe and other areas of the frontal lobe. In conclusion, theory of mind and emotion processing abilities are impaired in familial FTD, with early changes occurring prior to symptom onset in C9orf72 presymptomatic mutation carriers. Future work should investigate how performance changes over time, in order to gain a clearer insight into social cognitive impairment over the course of the disease

Hepatitis C viral load does not predict disease outcome: going beyond numbers A carga viral do vírus da hepatite C não prediz a evolução: indo além dos números

The analysis of 58 patients with chronic hepatitis C without cirrhosis and treated with interferon-alpha demonstrated that hepatitis C viral (HCV) load does not correlate with the histological evolution of the disease (p = 0.6559 for architectural alterations and p = 0.6271 for the histological activity index). Therefore, the use of viral RNA quantification as an evolutive predictor or determinant of the severity of hepatitis C is incorrect and of relative value. A review of the literature provided fundamental and interdependent HCV (genotype, heterogeneity and mutants, specific proteins), host (sex, age, weight, etc) and treatment variables (dosage, time of treatment, type of interferon) within the broader context of viral kinetics, interferon-mediated immunological response (in addition to natural immunity against HCV) and the role of interferon as a modulator of fibrogenesis. Therefore, viral load implies much more than numbers and the correct interpretation of these data should consider a broader context depending on multiple factors that are more complex than the simple value obtained upon quantification.<br>Através da análise de 58 pacientes tratados com Interferon Alfa em função de hepatite C crônica e sem cirrose, demonstramos que a carga viral do Vírus da Hepatite C (VHC) não se correlacionou com a evolução histológica da doença (p = 0,6559 para alterações arquiteturais e p = 0,6271 para o Índice de Atividade Histológica-IAH). Assim a utilização da quantificação do RNA viral como preditor evolutivo ou determinante da gravidade da hepatite C é incorreto e de valor relativo. Revisando o tema encontramos variáveis do VHC (genótipo, heterogeneidade e mutantes, proteínas específicas), do hospedeiro (sexo, idade, peso, etc) e dos medicamentos (posologia, tempo de tratamento, tipo de Interferon) fundamentais e interdependentes, inseridas no contexto mais amplo da cinética viral, da resposta imunológica mediada pelo Interferon (além da imunidade natural em resposta ao VHC) e do papel do Interferon como modulador da fibrogênese. Assim, há muito mais que números por trás da Carga Viral e sua correta interpretação deve ser feita considerando-se um horizonte mais amplo dependente de múltiplos fatores mais complexos que o simples valor obtido na quantificaçã