Progression in frontotemporal dementia: identifying a benign behavioral variant by magnetic resonance imaging.

Davies, Rhys R., Kipps, Christopher M., Mitchell, Joanna, Kril, Jilian J., Halliday, Glenda M. and Hodges, John R. (2006) Progression in frontotemporal dementia: identifying a benign behavioral variant by magnetic resonance imaging. Archives of Neurology, 63 (11), 1627-1631. (doi:10.1001/archneur.63.11.1627).

Abstract

Objective: to assess the clinical course and prognosis in patients with behavioral-variant frontotemporal dementia (FTD) lacking evidence of brain atrophy on magnetic resonance imaging (MRI).

Design: patients were enrolled into this prospective cohort study over a period of 15 years; cognitive status, duration of symptoms, and behavioral indexes were recorded. Brain MRIs were rated using a standardized scale.

Setting: regional early-onset dementia clinic.

Participants: thirty-one participants diagnosed clinically with behavioral-variant FTD.

Intervention: rating of MRIs.

Main outcome measures: death or institutionalization after a minimum of 3 years' follow-up indicated poor prognosis, while the ability to live independently was regarded as a good prognosis for the purpose of survival (Kaplan-Meier) and discriminant function analysis.

Results: patients with normal or borderline MRI findings (n = 15) showed significantly longer survival to institutionalization or death than those (n = 16) with definite frontotemporal atrophy (mean ± SE, 9.3 ± 1.7 years vs 3.0 ± 0.7 years; P<.01). Using groups defined by 3-year outcome (good or bad prognosis), cerebral atrophy predicted poor outcome while age, symptom duration, cognitive performance, behavioral impairment, and overall disability at baseline did not.

Conclusions: patients with FTD with normal MRI results follow a more benign course than cases with atrophy at presentation. The substrate of the behavioral symptoms in such cases may differ from the neurodegenerative pathological features typically associated with FTD.

Following a diagnosis of dementia, questions regarding prognosis inevitably arise. In the case of frontotemporal dementia (FTD), the second most prevalent early-onset dementia,1 the outlook is particularly poor, with recent reports indicating a median survival of just 3 years following clinical presentation.2,3

Several clinical variants of FTD are described. The behavioral variant (bvFTD), characterized by progressive changes in personality including disinhibition, apathy, loss of empathy, altered eating patterns, and stereotyped behavior, is most common.4 Two aphasic variants are also recognized: progressive nonfluent aphasia5 and semantic dementia.6 Post-mortem findings in FTD consistently include frontotemporal atrophy with severe neuronal loss, although the accompanying inclusion pathological features are heterogeneous.7 In vivo volumetric studies demonstrate that focal brain atrophy can be severe, even at the time of diagnosis, and that this feature may help to distinguish between FTD and other dementing conditions.8,9 Furthermore, the pattern of atrophy in FTD varies according to clinical features.10,11 Cases with bvFTD tend to show frontal or right temporal lobar atrophy.10 Current consensus criteria, however, do not mandate abnormal imaging findings; such changes are merely supportive of the diagnosis.4,12 Thus, a number of patients formally diagnosed with FTD have normal structural imaging findings.

Our clinical experience suggests the existence of a subgroup of patients with bvFTD with a substantially better prognosis than the literature implies. Since the identification of such patients might have profound consequences for patients and their families, we were interested in exploring whether specific imaging or demographic features could predict prognosis and to what extent our clinical observations could be formally substantiated. We hypothesized that patients fulfilling clinical criteria for bvFTD but lacking evidence of frontotemporal atrophy on magnetic resonance imaging (MRI) would have prolonged survival.

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Contributors

Author: Christopher M. Kipps

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