Frontotemporal Dementia

Clinical Neuroscience Group, Hope Hospital, Salford, Greater Manchester M6 8HD, UK.
The Lancet Neurology (Impact Factor: 21.9). 12/2005; 4(11):771-80. 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.

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    • "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. "
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    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 · Stem Cell Reports
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    • "It is noteworthy that these more severely-unwell schizophrenia patients are often excluded from research studies investigating cognition because of issues with " testability " and compliance. FTD, a younger-onset dementia, is the most common clinical syndrome associated with frontotemporal lobar degeneration (Neary et al., 2005). This pattern of neurodegeneration may manifest clinically as bvFTD or as one of several variants of language disorders – semantic dementia (SD), progressive non-fluent aphasia (PNFA), and logopenic progressive aphasia (LPA) (Gorno‐Tempini et al., 2004; Gorno-Tempini et al., 2011). "
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    ABSTRACT: This study focuses on a group of patients with chronic schizophrenia who have a more severe form of the disorder, as indicated by socio-functional decline, treatment resistance, and recurrent hospitalisation. Previous research has suggested that the pattern and severity of cognitive deficits in people with severe chronic schizophrenia is similar to that observed in behavioural variant frontotemporal dementia (bvFTD). In the current study, we compared neurocognitive performance in 16 cognitive domains in 7 inpatients with severe chronic schizophrenia, 13 community-dwelling outpatients with chronic schizophrenia, 12 patients with bvFTD, and 18 healthy controls. Our findings revealed more similar cognitive profiles between the schizophrenia inpatient and bvFTD groups compared to the schizophrenia outpatient group, who outperformed the former groups. The current results provide preliminary evidence for a distinct schizophrenia subgroup, distinguishable from other chronic schizophrenia patients by poorer clinical and functional status, who have levels of cognitive impairment comparable to those seen in bvFTD patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Dec 2014 · Psychiatry Research
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    • "Contents lists available at ScienceDirect journal homepage: and impulsivity, lack of insight, and emotional blunting, callousness , and a loss of empathy (Gustafson, 1987; Neary et al., 2005). Notably, patients with semantic dementia with right temporal lobe atrophy also tend to demonstrate similar behavioural symptoms early in the course of illness (Bozeat et al., 2000; Seeley et al., 2005; Snowden et al., 2001), and all three subtypes can include these behavioural abnormalities (Neary et al., 1998; Rosen et al., 2006). "
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    ABSTRACT: Objectives: Behavioural variant frontotemporal dementia (bvFTD) is a debilitating neurodegenerative disorder characterized by frontal and temporal lobe atrophy primarily affecting social cognition and emotion, including loss of empathy. Many consider empathy to be a multidimensional construct, including cognitive empathy (the ability to adopt and understand another's perspective) and emotional empathy (the capacity to share another's emotional experience). Cognitive and emotional empathy deficits have been associated with bvFTD; however, little is known regarding the performance of patients with bvFTD on behavioural measures of emotional empathy, and whether empathic responses differ for negative versus positive stimuli. Methods: 24 patients with bvFTD and 24 healthy controls completed the Multifaceted Empathy Test (MET; Dziobek et al., 2008), a performance-based task that taps both cognitive and emotional facets of empathy, and allows for the discrimination of responses to negative versus positive realistic images. MET scores were also compared with caregiver ratings of patient behaviour on the Interpersonal Reactivity Index, which assesses patients' everyday demonstrations of perspective taking and empathic concern. Results: Patients with bvFTD were less accurate than controls at inferring mental states for negative and positive stimuli. They also demonstrated lower levels of shared emotional experience, more positive emotional reactions, and diminished arousal to negative social stimuli relative to controls. Patients showed reduced emotional reactions to negative non-social stimuli as well. Lastly, the MET and IRI measures of emotional empathy were found to be significantly correlated within the bvFTD group. Conclusions: The results suggest that patients with bvFTD show a global deficit in cognitive empathy, and deficient emotional empathy for negative, but not positive, experiences. Further, a generalized emotional processing impairment for negative stimuli was observed, which could contribute to the emotional empathy deficit. This work highlights potential treatment targets and a means to assess the impact of novel therapies on socioemotional impairment in bvFTD.
    Full-text · Article · Nov 2014 · Neuropsychologia
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