Frontotemporal Dementia

ArticleinThe Lancet Neurology 4(11):771-80 · December 2005with13 Reads
DOI: 10.1016/S1474-4422(05)70223-4 · Source: PubMed
Frontotemporal dementia (FTD) is a focal clinical syndrome characterised by profound changes in personality and social conduct and associated with circumscribed degeneration of the prefrontal and anterior temporal cortex. Onset is typically in the middle years of life and survival is about 8 years. The presence of microtubule-associated-protein-tau-based pathological features in some patients and the discovery, in some familial cases, of mutations in the tau gene links FTD to other forms of tauopathy, such as progressive supranuclear palsy and corticobasal degeneration. However, more than half of all patients with FTD, including some with a strong family history, show no apparent abnormality in the tau gene or protein, indicating pathological and aetiological heterogeneity. FTD provides a challenge both for clinical management and for theoretical understanding of its neurobiological substrate.
    • "The behavioral variant (bv-FTD) is characterized by striking personality changes such as apathy, breakdown in social conduct and abulia. Patients develop social disinhibition and impulsivity and most patients seem unaware of their deficits [11,12]. Luzzi et al [9] describe a small study in which they compared the olfactory functioning in patients with AD, semantic dementia variant of FTD, bv-FTD and corticobasal degeneration. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: Several neurodegenerative disorders show olfactory dysfunction. In patients with frontotemporal dementia (FTD), olfactory impairment is probably due to the involvement of the temporal and orbitofrontal lobes. We hypothesized that due to the disrupted areas in FTD, there would be an impairment in smell identification, differentiation and association. Moreover, we hypothesized that there would be a correlation between the severity of FTD and the severity of odor dysfunction. Methods: In the current study, we compared odor identification, discrimination and association of nine patients with behavioral variant FTD with eleven healthy controls using the Brief Smell Identification Test and the Odor Perception and Semantics Battery. Results: The results showed significant differences in the odor association test, but not in the identification or discrimination test. There was no correlation between disease severity and the performance in the odor tests. Conclusion: We showed impairment of odor association that is most likely due to disruption of specific associative areas involved in olfactory processing. Specifically, we propose that the impairment may well be due to disrupted areas in the temporal lobe and amygdala.
    Full-text · Article · Feb 2016
    • "The latter difficulties pertain to language use that requires an appreciation of non-literal speaker's intentions, as in the cases of sarcasm, indirect requests, metaphors, and humour interpretation (thus outside the domains of standard syntactical, phonological, or semantical level of linguistic processing). Another source of information on neural structures supporting our social interactive abilities comes from patients suffering frontotemporal dementia (FTD), a deterioration of the ventral base of the frontal lobe progressing towards the anterior temporal lobes (Snowden, Neary, & Mann, 2002). The analyses of the neurobiology of these patients reveal that intrinsically motivated social relationships are affected when the frontal lobe and right temporal pole degenerate (Fiske, 2010). "
    [Show abstract] [Hide abstract] ABSTRACT: Despite the multiple semantic ambiguities present in every utterance during natural language use, people are remarkably efficient in establishing mutual understanding. This chapter illustrates how the study of human communication in novel settings provides a window into the mechanisms supporting the human competence to rapidly generate and understand novel shared symbols, capturing the joint construction of meaning across interacting agents. In this chapter, we discuss empirical findings and computational hypotheses generated in the context of an experimentally-controlled non-verbal interactive task that throw light on these fundamental properties of human referential communication. The neural evidence reviewed here points to mechanisms shared across interlocutors of a communicative interaction. Those neural mechanisms implement predictions based on presumed knowledge and beliefs of the communicative partner. Computationally, the generation of novel meaningful symbolic representations might rely on cross-domain analogical mappings. Those mappings provide a mechanism for systematically augmenting individual pre-existing representations, adjusting them to the current conversational context.
    Full-text · Chapter · Apr 2015 · Stem Cell Reports
    • "Human somatic cell reprogramming to a pluripotent state (induced pluripotent stem cells; iPSCs)(Takahashi et al., 2007a) can create human disease models in vitro using patient-derived iPSCs (Kim, 2014), including neurodegenerative diseases (Qiang et al., 2013) and, specifically, FTD (Almeida et al., 2012). Unlike in the published FTDiPSC model that differentiated iPSCs to a mixture of neuronal cells, we evaluated cortical neuron development from FTD-patient-derived iPSCs, as FTD is characterized by selective neurodegeneration of the frontal and/or temporal cortex (Neary et al., 2005). We demonstrate that FTD-iPSCs carrying a GRN IVS1+5G > C mutation differ in their ability to generate cortical neurons from control lines (iPSCs and human embryonic stem cells; hESCs) and that genetic correction restores this differentiation defect. "
    [Show abstract] [Hide abstract] ABSTRACT: Frontotemporal dementia (FTD) accounts for ∼50% of dementia cases before the age of 60. Up to 40% of FTD patients have a familial history (Goldman et al., 2005 and van Swieten and Heutink, 2008) due to mutations in the microtubule-associated protein tau gene (MAPT), progranulin gene (GRN), or C9orf72 gene (Baker et al., 2006, Cruts et al., 2006, DeJesus-Hernandez et al., 2011, Hutton et al., 1998 and Renton et al., 2011). The majority of FTD-causing mutations in GRN are predicted to result in functional null alleles, causing haploinsufficiency. Progranulin (PGRN) has neurotrophic function in vitro and in vivo. Although PGRN−/− mice are viable, they do not recapitulate all the features of FTD (Kayasuga et al., 2007).
    Full-text · Article · Dec 2014
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