Different anatomical subtypes of behavioral variant frontotemporal dementia identified using cluster analysis

Abstract

The behavioral variant of frontotemporal dementia (bvFTD) is a progressive neurodegenerative disorder characterized by changes in personality and behavior. It is typically associated with frontal lobe atrophy, although patterns are heterogeneous. The objective of this study was to examine case-by-case variability in patterns of grey matter atrophy in subjects with bvFTD and to investigate whether bvFTD can be divided into distinct anatomical subtypes. Sixty-six subjects that fulfilled clinical criteria (Neary et al 1998) for a diagnosis of bvFTD and had a volumetric MRI scan were identified. Grey matter volumes were obtained for 26 regions-of-interest, covering frontal, temporal and parietal lobes, striatum, insula and supplemental motor area, using the automated anatomical labeling atlas. Regional volumes were adjusted by total grey matter volume. A hierarchical agglomerative cluster analysis was performed to create a series of nested clusters starting off with each patient in his/her own cluster and ending with all patients combined into a single cluster. Wards' clustering linkage method was then used to combine clusters based on minimizing the sum of square errors from the cluster mean. Voxel-based morphometry was then used to assess patterns of grey matter loss in subjects assigned to each identified cluster compared to age and gender-matched controls (p<0.01, FDR corrected). We identified two main clusters (A and B), each of which has two distinct sub clusters (A1, A2, B1 and B2, Figure). Cluster A was characterized by predominant temporal atrophy, with A1 showing loss restricted to temporal regions and A2 showing temporal loss as well as loss of the frontal and parietal lobes. Cluster B was characterized by predominant frontal atrophy, with B1 showing frontal loss as well as loss of the temporal lobes and B2 showing loss relatively restricted to frontal regions. These clusters differed on clinical measures of executive function, episodic memory and confrontational naming. However, the clusters did not differ in behavioral severity as measured by the Neuropsychiatric Inventory. Behavioral variant FTD can be subdivided into four different anatomical subtypes: two temporal dominant and two frontal dominant. Behavioral severity was similar across all subtypes validating the original classification of bvFTD in these subjects.