Neuroanatomical correlates of behavioural phenotypes in behavioural variant of frontotemporal dementia

Abstract

BackgroundBehavioural variant of frontotemporal dementia (bvFTD) frequently presents complex behavioural changes, that rarely occur in isolation. Targeting behavioural phenotypes instead of single behavioural symptoms may potentially provide a disease model in which to investigate brain substrates of behavioural abnormalities. ObjectiveTo identify behavioural phenotypes and to assess the associated brain correlates in a cohort of patients with bvFTD. MethodsTwo hundred and seven consecutive individuals fulfilling clinical criteria for bvFTD were enrolled. Each participant's caregiver completed frontal behavioural inventory on 24 key behavioural disturbances. Confirmatory factor analysis (CFA) models were applied, and behavioural phenotypes identified. For each phenotype, a score was derived based on the “best” CFA model (Bifactor CFA). One hundred two participants underwent SPECT scan. A regression analysis between scores for each factor and regional cerebral blood flow was carried out (P<0.001). ResultsOne “general” behavioural phenotype and four factors were identified, that were termed “disinhibited”, “apathetic”, “aggressive”, and “language” phenotypes. The most robust brain correlate was identified for “disinhibited” phenotype, in the region of the anterior cingulated and anterior temporal cortex, bilaterally, and for apathetic phenotype in the left dorsolateral frontal cortex. As expected, language phenotype correlated with greater hypoperfusion in the left frontotemporal lobes. No significant correlation between aggressive phenotype and regional cerebral blood flow was found. Moreover, the “general” behavioural severity was associated with greater damage in the right frontal lobe. ConclusionsBehavioural phenotypes are associated with specific brain damage in bvFTD, involving distinct cerebral networks.