Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia

Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, 3 West Gates, Philadelphia, PA 19104, USA.
Brain (Impact Factor: 9.2). 08/2011; 134(Pt 9):2456-77. DOI: 10.1093/brain/awr179
Source: PubMed


Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.

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    • "In addition to the predominance of early memory deficits in female patients and the link with positive Pick body pathology, another characteristic of the patients with an early amnestic syndrome was the greater age at onset than that observed in patients who initially developed behavioral disturbances. This observation is in agreement with previous research[1,31]and could reflect an increased vulnerability of memory-related brain regions in older patients due to an interaction of the pathophysiology of FTD with aging processes that especially affect the functioning of episodic memory[20,24]. The analysis showed similar duration of disease among the three groups of patients with the main patterns of clinical symptomatology. "
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    ABSTRACT: Recent accumulated evidence indicates that episodic memory impairments could be part of the initial clinical expression of frontotemporal dementia (FTD). An early study on this issue was carried out by Constantinidis and colleagues in 1974, but it was subsequently overlooked for a long period of time. The scope of the present research was: (a) to explore the presence of early episodic memory impairments in the entire population of neuropathologically confirmed FTD patients from the Geneva brain collection; and (b) to expand the present insight on the association between the initial symptomatology and various characteristics, namely gender, age at onset, disease duration, and presence of Pick body neuropathology. A careful review of the records of 50 FTD patients hospitalized at the Department of Psychiatry of the Bel-Air Hospital, Geneva, Switzerland, from 1929 to 1999, was conducted. Further in-depth neuropathological analysis with novel immunohistological methods was carried out in 37 of the cases. The data showed that memory impairments were the first clinical symptom in several of the patients. In addition, this specific phenotypic expression of FTD was associated with the female gender, advanced age, and positive Pick body neuropathology. The current findings give the opportunity to historically vindicate the early work of Constantinidis and colleagues. In addition, the novel observations about the association of episodic memory impairments with the female gender and positive Pick body neuropathology add to the existing knowledge about this phenotypic expression of FTD.
    Full-text · Article · Jan 2016 · Journal of Neurology
    • "Twenty-four patients with behavioral variant frontotemporal dementia (bvFTD), 14 patients with semantic variant primary progressive aphasia (svPPA), and 18 patients with nonfluent variant primary progressive aphasia (nfvPPA) were recruited via a tertiary cognitive disorders clinic as part of a cross-sectional and longitudinal cognitive and neuroimaging study of frontotemporal lobar degeneration. All patients fulfilled current consensus criteria for a probable or definite syndromic diagnosis [1, 23] corroborated by general neuropsychological assessment. Genetic screening of the patient cohort revealed pathogenic mutations in 11 cases (five C9orf72, four bvFTD, one nfvPPA; six MAPT, all bvFTD). "
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    ABSTRACT: Background: The language profile of behavioral variant frontotemporal dementia (bvFTD) remains to be fully defined. Objective: We aimed to quantify the extent of language deficits in this patient group. Methods: We assessed a cohort of patients with bvFTD (n = 24) in relation to patIents with semantic variant primary progressive aphasia (svPPA; n = 14), nonfluent variant primary progressive aphasia (nfvPPA; n = 18), and healthy age-matched individuals (n = 24) cross-sectionally and longitudinally using a comprehensive battery of language and general neuropsychological tests. Neuroanatomical associations of language performance were assessed using voxel-based morphometry of patients' brain magnetic resonance images. Results: Relative to healthy controls, and after accounting for nonverbal executive performance, patients with bvFTD showed deficits of noun and verb naming and single word comprehension, diminished spontaneous propositional speech, and deterioration in naming performance over time. Within the bvFTD group, patients with MAPT mutations had more severe impairments of noun naming and single word comprehension than patients with C9orf72 mutations. Overall the bvFTD group had less severe language deficits than patients with PPA, but showed a language profile that was qualitatively similar to svPPA. Neuroanatomical correlates of naming and word comprehension performance in bvFTD were identified predominantly in inferior frontal and antero-inferior temporal cortices within the dominant hemispheric language network. Conclusions: bvFTD is associated with a language profile including verbal semantic impairment that warrants further evaluation as a novel biomarker.
    No preview · Article · Dec 2015 · Journal of Alzheimer's disease: JAD
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    • "Table 4reports the comparison between EMS and individual memory scores obtained at baseline in detecting conversion to dementia. The scores obtained on RAVLT and ROCF delayed recall were corrected for age and literacy according to the respective normative studies[25,38]. For most of the possible cut-off points, the EMS showed high sensitivity, with at least acceptable levels of specificity, that were always higher than those observed in the individual memory tasks. The classification accuracy of the EMS and memory tasks was also compared by computing ROC curves, and estimating the respective area under the curve (AUC). "
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    ABSTRACT: Taking into the account both the severity and the consistency of performances obtained on memory test by patients with amnestic mild cognitive impairment (aMCI) could improve the power to predict their progression to Alzheimer's disease. For this purpose, we constructed the Episodic Memory Score (EMS), which is obtained by subdividing in tertiles performances obtained at baseline in verbal (RAVLT) and visual episodic memory (Rey-Osterrieth Figure-delayed recall) and giving a score ranging from 1 (worst result) to 3 (best result) to results falling within each tertile. The EMS was computed for each patient by summing the tertile score obtained on each memory task, so that the total score ranged from 4 (worst performance) to 12 (best performance). The aMCI sample consisted of 198 subjects who completed the two-year follow-up, at the end of which 55 subjects had converted to dementia. The mean EMS score obtained by aMCI converters was significantly lower than that of aMCI-stable patients. In detecting conversion to dementia, the comparison between EMS and individual memory scores obtained at baseline was made by computing ROC curves, and estimating the respective area under the curve (AUC). The EMS had a larger AUC than the individual memory scores. At baseline aMCI converters performed worse than non-converters not only on memory tasks, but also on executive functions tasks. However, in a multiple variables logistic regression analysis in which all scores showing statistically significant differences between aMCI-converters and aMCI-stable were entered, the EMS was the only reliable predictor of progression from aMCI to dementia.
    Full-text · Article · Dec 2015 · Journal of Alzheimer's disease: JAD
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