The most widely established diagnostic criteria for the behavioral variant of frontotemporal dementia have now been in use for almost a decade. Although consensus criteria have provided a much needed standard for frontotemporal dementia research, a growing body of evidence suggests that revisions are needed to improve their applicability. In this article, we discuss the limitations of current diagnostic criteria and propose the establishment of an international consortium to revise diagnostic and research criteria for the behavioral variant of frontotemporal dementia.

Recent publications estimate the prevalence of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) exceeds 50%, and this rate is likely higher among older patients. Cognitive impairment may impact medication adherence, and symptomatic impairment has been linked to all-cause mortality providing some impetus for early detection. There are currently insufficient data to inform solid recommendations on screening methods. Most HIV-specific tools have poor performance characteristics for all but the most severe form of impairment, which accounts for <5% of cases. Reliance on symptoms is likely to miss a substantial proportion of individuals with HAND due to poor insight, confounding mood disturbances, and lack of well-informed proxies. In the aging HIV-positive population, broader screening tools may be required to allow sensitivity for both HIV and neurodegenerative disorders. We describe the clinical presentation of HAND, review existing data related to screening tools, and provide preliminary and practical recommendations in the absence of more definitive studies.

V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutated lung cancer is relatively aggressive and is resistant to currently available therapies. In a recent phase II study for patients with BRAF-V600E non-small cell lung cancer (NSCLC), BRAF V600E inhibitor demonstrated evidence of activity, but 30% of this selected group progressed while on treatment, suggesting a need for developing alternative strategies. We tested two different options to enhance the efficacy of vemurafenib (BRAF V600E inhibitor) in BRAF mutated NSCLC. The first option was the addition of erlotinib to vemurafenib to see whether the combination provided synergy. The second was to induce MEK inhibition (downstream of RAF) with trametinib (MEK inhibitor). We found that the combination of vemurafenib and erlotinib was not synergistic to the inhibition of p-ERK signaling in BRAF-V600E cells. Vemurafenib caused significant apoptosis, G1 arrest and upregulation of BIM in BRAF-V600 cells. Trametinib was effective as a single agent in BRAF mutated cells, either V600E or non-V600E. Finally, the combination of vemurafenib and trametinib caused a small but significant increase in apoptosis as well as a significant upregulation of BIM when compared to either single agent. Thus, hinting at the possibility of utilizing a combinational approach for the management of this group of patients. Importantly, trametinib alone caused upregulation of p-AKT in BRAF non-V600 mutated cells, while this effect was nullified with the combination. This finding suggests that, the combination of a MEK inhibitor with a BRAF inhibitor will be more efficacious in the clinical setting for patients with BRAF mutated NSCLC.

Interest in the neuropsychology and neuropsychiatry of frontotemporal dementia (FTD) has escalated in the past decade, as evidenced by the accompanying 10 special topic papers from research groups in the UK, France, North America and Australia addressing a wide range of theoretical and clinical issues. The first part of this review deals with the confusing terminologies that have been used in the area and argues for the retention of the term FTD as the general clinical label, with further subcategorization into the three principal clinical syndromes seen at presentation: frontal variant FTD (often called dementia of frontal type), semantic dementia and progressive non-fluent aphasia. Each of these syndromes has a characteristic profile of presenting clinical features, but may be accompanied by any one of five types of non-Alzheimer pathological change. There have also been significant advances in the genetics of FTD with the identification of tau gene mutations on chromosome 17 in some familial cases. The remarkable story of the discovery of these, the tau gene mutations, is briefly described. Part II of this review (Hodges and Miller, 2001) sets the special issue papers within the context of advances in the neuropsychology of frontal variant FTD and semantic dementia.