Behavioural-variant frontotemporal dementia: Diagnosis, clinical staging, and management

Neuroscience Research Australia, Randwick, NSW, Australia.
The Lancet Neurology (Impact Factor: 21.9). 02/2011; 10(2):162-72. DOI: 10.1016/S1474-4422(10)70299-4
Source: PubMed

ABSTRACT Patients with behavioural-variant frontotemporal dementia (bvFTD) present with insidious changes in personality and interpersonal conduct that indicate progressive disintegration of the neural circuits involved in social cognition, emotion regulation, motivation, and decision making. The underlying pathological changes are heterogeneous and are characterised by various intraneuronal inclusions. Biomarkers to detect these histopathological changes in life are becoming increasingly important with the development of disease-modifying drugs. Gene mutations have been found that collectively account for around 10-20% of cases. Recently, criteria proposed for bvFTD define three levels of diagnostic certainty: possible, probable, and definite. Detailed history taking from family members to elicit behavioural features underpins the diagnostic process, with support from neuropsychological testing designed to detect impairment in decision making, emotion processing, and social cognition. Brain imaging is important for increasing the level of diagnostic certainty. A recently developed staging instrument shows much promise for monitoring patients and evaluating therapies, which at present are aimed at symptom amelioration. Carer education and support remain of paramount importance.

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    • "Frontal and temporal neural circuitry has been implicated in the pathophysiology of behaviours such as impulsivity and aggression (Weiger and Bear 1988; Snowden et al. 2001; Winstanley et al. 2004). The uncinate fasciculus (UF) is a major white matter (WM) tract that bidirectionally connects the medial and lateral OFC with the ATL (Catani et al. 2002; Schmahmann et al. 2007), and is implicated in impulsivity, described in studies of frontotemporal dementia (Piguet et al. 2011) and in schizophrenia (Hoptman et al. 2002). Individuals having sustained concussions often exhibit behavioural changes including impulsivity, depression and aggression (Bigler 2007; Silver et al. 2009), and the UF has been implicated in concussion (Smits et al. 2011). "
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    ABSTRACT: The frontotemporal cortical network is associated with behaviours such as impulsivity and aggression. The health of the uncinate fasciculus (UF) that connects the orbitofrontal cortex (OFC) with the anterior temporal lobe (ATL) may be a crucial determinant of behavioural regulation. Behavioural changes can emerge after repeated concussion and thus we used MRI to examine the UF and connected gray matter as it relates to impulsivity and aggression in retired professional football players who had sustained multiple concussions. Behaviourally, athletes had faster reaction times and an increased error rate on a go/no-go task, and increased aggression and mania compared to controls. MRI revealed that the athletes had (1) cortical thinning of the ATL, (2) negative correlations of OFC thickness with aggression and task errors, indicative of impulsivity, (3) negative correlations of UF axial diffusivity with error rates and aggression, and (4) elevated resting-state functional connectivity between the ATL and OFC. Using machine learning, we found that UF diffusion imaging differentiates athletes from healthy controls with significant classifiers based on UF mean and radial diffusivity showing 79-84 % sensitivity and specificity, and 0.8 areas under the ROC curves. The spatial pattern of classifier weights revealed hot spots at the orbitofrontal and temporal ends of the UF. These data implicate the UF system in the pathological outcomes of repeated concussion as they relate to impulsive behaviour. Furthermore, a support vector machine has potential utility in the general assessment and diagnosis of brain abnormalities following concussion.
    Brain Structure and Function 02/2015; DOI:10.1007/s00429-015-1012-0 · 5.62 Impact Factor
    • "The study of brain cerebral blood flow with single-photon emission computed tomography (SPECT) revealed the presence of hypoperfusion in the anterior cingulate and left dorsolateral frontal cortex (Fig. 2B). The presence of slowly progressive behavioral disorders in the spectrum of apathy and impulsive/compulsive manifestations, disexecutive cognitive impairment, and neuroimaging evidence of frontal lobe dysfunction satisfied the criteria for probable bvFTD [1] [2]. A therapeutic attempt to control the binge-eating disorder switching fluoxetine to fluvoxamine (up to 100 mg/day) stabilized the patient's body weight, although the patient was still repetitively asking for food. "
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    ABSTRACT: Objective To describe a patient with behavioral frontotemporal dementia (bvFTD) presenting with impulse control disorders (ICDs) which responded to fluvoxamine and topiramate. Case report A 64 year-old woman was affected by complained of several ICDs. At disease onset she complained suffered fromof impulsive smoking and overeating that which caused 20 kg increase ofa body weight increase of 20 kg in 6 months. Later on she manifested binge-eating behavior and skin picking disordercompulsion. Presence ofA progressive frontal disexecutive cognitive impairment (MMSE 24/30) and evidence of hypoperfusion of the anterior cingulate cortex and dorsolateral frontal cortex detected with brain SPECT scan contributed to the diagnosis of bvFTD. Use of combination treatment with SSRI drugs and topiramate as add-on therapy could control improved all these symptoms. Conclusion This case extends the clinical phenotype of repetitive and compulsive habits in bvFTD to encompass symptoms suggestive of ICDs. It is proposed that fluvoxamine and topiramate may be considered as treatment options in these conditions.
    General Hospital Psychiatry 11/2014; 36(6). DOI:10.1016/j.genhosppsych.2014.06.005 · 2.61 Impact Factor
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    • "Patients with bvFTD display a diminished response to other's feelings and a diminished social interest or personal warmth (Mendez, 2006; Rankin et al., 2006). From a clinical perspective, empathy changes influence the interpersonal judgment, emotions , behavior, and social functioning of bvFTD patients (Lough et al., 2006; Piguet et al., 2011; Rascovsky et al., 2011). In spite of its relevance, the study of empathy in bvFTD patients using experimental designs has been scarce, and no studies have explored whether relevant factors (Gregory et al., 2002; Possin et al., 2013) such as executive functions (EF) and other social cognition domains (OSCD) impact the empathic abilities of these patients. "
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    ABSTRACT: Loss of empathy is an early central symptom and diagnostic criterion of the behavioral variant frontotemporal dementia (bvFTD). Although changes in empathy are evident and strongly affect the social functioning of bvFTD patients, few studies have directly investigated this issue by means of experimental paradigms. The current study assessed multiple components of empathy (affective, cognitive and moral) in bvFTD patients. We also explored whether the loss of empathy constitutes a primary deficit of bvFTD or whether it is explained by impairments in executive functions (EF) or other social cognition domains. Thirty-seven bvFTD patients with early/mild stages of the disease and 30 healthy control participants were assessed with a task that involves the perception of intentional and accidental harm. Participants were also evaluated on emotion recognition, theory of mind (ToM), social norms knowledge and several EF domains. BvFTD patients presented deficits in affective, cognitive and moral aspects of empathy. However, empathic concern was the only aspect primarily affected in bvFTD that was neither related nor explained by deficits in EF or other social cognition domains. Deficits in the cognitive and moral aspects of empathy seem to depend on EF, emotion recognition and ToM. Our findings highlight the importance of using tasks depicting real-life social scenarios because of their greater sensitivity in the assessment of bvFTD. Moreover, our results contribute to the understanding of primary and intrinsic empathy deficits of bvFTD and have important theoretical and clinical implications.
    Frontiers in Aging Neuroscience 10/2014; 6:262. DOI:10.3389/fnagi.2014.00262 · 4.00 Impact Factor
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