Combined magnetic resonance imaging and positron emission tomography brain imaging in behavioural variant frontotemporal degeneration: refining the clinical phenotype.

In patients with the behavioural variant of frontotemporal dementia, prognosis is often surprisingly good when there is normal structural imaging at presentation. Imaging abnormalities are not, however, mandatory for diagnosis, which in the absence of suitable biomarkers, remains entirely clinical. We aimed to test whether cases with normal structural imaging have hypometabolism suggestive of underlying neurodegeneration, or whether it is likely that such patients are false positive diagnoses of behavioural variant frontotemporal dementia. Patients with this disease (n = 24) and age-matched controls (n = 12) underwent both magnetic resonance imaging (MRI) and quantitative fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning, together with clinical and behavioural assessments. Regions of interest were used to calculate metabolic rate in frontotemporal and control regions. Using a semi-quantitative visual rating scale, patients were divided into MRI-abnormal (n = 15) and MRI-normal groups (n = 9). There was definite frontotemporal hypometabolism in the MRI-abnormal group (particularly in the mesial and orbitofrontal regions) even after accounting for brain volume loss, whereas the MRI-normal group was similar to controls in all regions. In contrast, cognitive and behavioural indices did not separate the two behavioural variant frontotemporal dementia patient groups. The results suggest that the clinical syndrome of the behavioural variant of frontotemporal dementia may not be specific for a neurodegenerative disease, and we hypothesize the existence of a phenocopy. A number of alternative neuropsychiatric and developmental explanations are discussed. We advise caution in diagnosing the illness in patients without imaging abnormalities, and propose that imaging findings are included in criteria for diagnosis.