Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia

Abstract

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.

Figure 1

Case selection and description of samples. bvFTD = behavioural variant FTD; F&I = functional disability and neuroimaging.

Figure 2

Sensitivity of FTDC and 1998 criteria as per cent of cases that met criteria in the corresponding sample (white bars) or the common sample (black bars). bvFTD = behavioural variant FTD.

Figure 3

Frequency of individual features for (A) possible bvFTD, (B) probable bvFTD and (C) 1998 core criteria. Frequency is shown as percentage of cases in the corresponding sample (white bars) or the common sample (black bars). bvFTD = behavioural variant FTD; F&I = functional disability and neuroimaging.

Figure 4

Frequency of exclusionary features for (A) FTDC criteria and (B) 1998 criteria. Frequency is shown as percentage of cases in the corresponding sample (clear bars) or the common sample (black bars). Two cases were homozygous for the ApoE e4 allele, but ApoE status was not considered a strong biomarker for Alzheimer’s disease (AD).

Figure 5

Sensitivity of FTDC and 1998 criteria by number of features for (A) FTDC possible behavioural variant FTD and (B) 1998 criteria (common sample, n = 137). Black bars show percent of cases with specified number of diagnostic features and no exclusion features.