Clinical heterogeneity of the C9orf72 genetic mutation in frontotemporal dementia

The C9orf72 genetic mutation represents the most common cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Studies over the last 2 years have revealed a number of key features of this mutation in the fields of clinical neurology, imaging, pathology, and genetics. Despite these efforts, the clinical phenotype appears to extend beyond FTD and ALS into the realm of psychiatric disease, and while highly variable survival rates have been reported, the clinical course of carriers remains relatively unexplored. This report describes two contrasting C9orf72 cases, one with a protracted indolent course dominated by neuropsychiatric features and the other with a rapidly progressive dementia. In both cases, initial structural brain imaging was relatively normal.     

Mass drug administration significantly reduces infection of <Emphasis Type="Italic">Schistosoma mansoni</Emphasis> and hookworm in school children in the national control program in Sierra Leone

Background  

The first-ever round of school-based mass drug administration (MDA) with praziquantel together with mebendazole targeting school-aged children in endemic districts was conducted in 2009 by the National Neglected Tropical Diseases Control Program. To evaluate the impact of the treatment regimen, a cross-sectional sentinel site survey was conducted 6 months post-MDA.     

Histamine regulation of pancreatitis and pancreatic cancer: a review of recent findings

The pancreas is a dynamic organ that performs a multitude of functions within the body. Diseases that target the pancreas, like pancreatitis and pancreatic cancer, are devastating and often fatal to the suffering patient. Histamine and histamine receptors (H1-H4HRs) have been found to play a critical role in biliary diseases. Accordingly, the biliary tract and the pancreas share similarities with regards to morphological, phenotypical and functional features and disease progression, studies related the role of H1-H4HRs in pancreatic diseases are important. In this review, we have highlighted the role that histamine, histidine decarboxylase (HDC), histamine receptors and mast cells (the main source of histamine in the body) play during both pancreatitis and pancreatic cancer. The objective of the review is to demonstrate that histamine and histamine signaling may be a potential therapeutic avenue towards treatment strategies for pancreatic diseases.Key Words: Histamine, pancreas, pancreatitis, pancreatic cancer     

Episodic future thinking is impaired in the behavioural variant of frontotemporal dementia

Remembering the past and imagining the future are complex endeavours proposed to rely on a core neurobiological brain system. In the behavioural variant of frontotemporal dementia (bvFTD), regional patterns of brain atrophy affect medial prefrontal and temporal cortices of this core network. While autobiographical memory impairments have been documented in bvFTD, it remains unknown whether the ability to imagine future events is also compromised. Here, we investigated episodic future thinking in 10 bvFTD patients and contrasted their performance with Alzheimer's disease (AD, n = 10) and healthy matched Control (n = 10) participants. Participants were asked to remember 3 events from the previous year and to envisage 3 possible events that could occur in the next year. Both patient groups showed equivalent episodic detail performance for the retrieval of past events and the simulation of possible future episodes. Patients with bvFTD, however, showed additional impairments for the generation of external (non-episodic) details irrespective of condition. Voxel-based morphometry analyses revealed divergent neural correlates of episodic past and future thinking performance specific to each patient group. Atrophy in the posterior cingulate cortex was implicated in the disruption of past and future thinking in AD. In contrast, in bvFTD, disruption of past retrieval correlated with atrophy in medial prefrontal regions, whereas future thinking deficits were associated with atrophy of frontopolar, medial temporal regions including the right hippocampus, and lateral temporal and occipital cortices. Our results point to the involvement of multiple brain regions in facilitating retrieval of past, and simulation of future, events. Damage to any of these key regions thus adversely affects the ability to engage in personally relevant mental time travel.     

The treatment of object naming,definition, and object use in semantic dementia: The effectiveness of errorless learning

Background: Patients with semantic dementia are impaired in both object naming and, to a lesser extent, in object use (Bozeat, Lambon Ralph, Patterson, & Hodges, 2002a Bozeat, S., Lambon Ralph, M. A., Patterson, K. and Hodges, J. R. 2002a. When objects lose their meaning: What happens to their use?. Cognitive, Affective & Behavioural Neurosciences, 2: 236–251. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Hodges, Graham, & Patterson, 1995 Hodges, J. R., Graham, N. and Patterson, K. 1995. Charting the progression in semantic dementia: Implications for the organisation of semantic memory.. Memory, 3: 463–495. [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). To date there have been relatively few studies examining the relearning of object names, and only one examining the relearning of object use. No study has examined relearning object naming, definition, and use simultaneously.

Aims: To explore the relatedness of object naming, definition, and object use in semantic dementia; to explore whether or not therapy is effective; and to explore the effectiveness of errorless learning.

Methods & Procedures: Two patients with mild to moderate semantic dementia and two matched control participants were tested in naming, defining, and demonstrating the use of 33 household objects. The quality of the definitions was rated as poor, adequate, or good by three independent raters. Three components of object use were examined: hold, orientation, and movement. The assessment was repeated with the patients following 3 weeks of therapy, and 1 month after completion of therapy. For the therapy objects were divided into individual trained and untrained sets based on familiarity and performance at initial assessment. Patients received therapy sessions twice weekly, and engaged in independent practice. During the therapy sessions, the researcher modelled the name, definition, and use of each item, which the patient then repeated. In the independent practice each patient watched a DVD in which she named and defined the object and used it correctly.

Outcomes & Results: Patients were severely impaired on object naming and definition, but less so on object use. Both patients showed some improvement as a result of therapy, which was maintained at follow‐up in one case.

Conclusions: The results show that relearning in semantic dementia is possible. Factors affecting the results and the interaction between lexical and conceptual impairments are discussed. An unexpected finding of the study was that patients performed better in verb production both in the preliminary tests and in object definition.     

Is the Prevalence of Metabolic Syndrome and Metabolic Abnormalities Increased in Early Schizophrenia? A Comparative Meta-Analysis of First Episode,Untreated and Treated Patients

We aimed to discover whether metabolic complications of schizophrenia (SZ) are present in first episode (FE) and unmedicated (UM) patients, in comparison with patients established on antipsychotic medication (AP).

Method:

A systematic search, critical appraisal, and meta-analysis were conducted of studies to December 2011 using Medline, PsycINFO, Embase and experts. Twenty-six studies examined FE SZ patients (n = 2548) and 19 included UM SZ patients (n = 1325). For comparison we identified 78 publications involving 24 892 medicated patients who had chronic SZ already established on AP.

Results:

In UM, the overall rate of metabolic syndrome (MetS) was 9.8% using any standardized criteria. Diabetes was found in only 2.1% and hyperglycaemia (>100mg/dl) in 6.4%. In FE, the overall MetS rate was 9.9%, diabetes was found in only 1.2%, and hyperglycaemia in 8.7%. In UM and FE, the rates of overweight were 26.6%, 22%; hypertriglyceridemia 16.9%, 19.6%; low HDL 20.4%, 21.9%; high blood pressure 24.3%, 30.4%; smoking 40.2%, 46.8%, respectively. In both groups all metabolic components and risk factors were significantly less common in early SZ than in those already established on AP. Waist size, blood pressure and smoking were significantly lower in UM compared with FE.

Conclusion:

There is a significantly lower cardiovascular risk in early SZ than in chronic SZ. Both diabetes and pre-diabetes appear uncommon in the early stages, especially in UM. However, smoking does appear to be elevated early after diagnosis. Clinicians should focus on preventing initial cardiometabolic risk because subsequent reduction in this risk is more difficult to achieve, either through behavioral or pharmacologic interventions.Key words: cardiovascular risk, diabetes, lipids, glucose, waist, obesity     

Assessing awareness in early-stage Alzheimer's disease: Development and piloting of the Memory Awareness Rating Scale

There are indications that awareness may have an important impact on functioning and response to rehabilitative interventions in early-stage Alzheimer's disease (AD), yet studies have so far produced few clear findings, and a comprehensive explanatory model is needed together with a reliable assessment method. A theory-driven approach to assessing awareness in early-stage Alzheimer's disease was used to develop the Memory Awareness Rating Scale (MARS), a measure that addresses key methodological limitations of the assessment methods adopted in existing studies. The MARS was piloted with 12 couples where one partner had a diagnosis of AD. This demonstrated that the MARS has satisfactory psychometric properties, and suggested some refinements to the scale that may improve its usefulness. Results obtained with the MARS allow further consideration of theoretical and methodological issues that arise in attempting to understand and assess awareness. The development of this rigorous method of assessing awareness of memory difficulties in early-stage AD provides a basis for further investigation of the relationship between awareness of memory difficulties and outcome of neuropsychological rehabilitation in early-stage AD.