Behavioral-variant frontotemporal dementia: Distinct phenotypes with unique functional profiles

Claire M O'Connor, Ramon Landin-Romero, Lindy Clemson, Cassandra Kaizik, Naomi Daveson, John R Hodges, Sharpley Hsieh, Olivier Piguet, Eneida Mioshi

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Abstract

Objective: To identify distinct behavioral phenotypes of behavioral variant frontotemporal dementia (bvFTD), and elucidate differences in functional, neuroimaging, and progression to residential care placement.

Methods: Eighty-eight patients with bvFTD were included in a cluster analysis applying levels of disinhibition and apathy (Cambridge Behavioural Inventory-Revised) to identify phenotypic subgroups. Between-group (Kruskal-Wallis; Mann-Whitney U) functional differences (Disability Assessment for Dementia), and time to residential care placement (survival analyses) were examined. Cortical thickness differences (whole brain MRI) were analyzed in bvFTD patients versus healthy controls (n=30) and between phenotypic subgroups.

Results: Four phenotypic subgroups were identified: “Primary severe apathy” (n=26), “Severe apathy and disinhibition” (n=26), “Mild apathy and disinhibition” (n=27), “Primary severe disinhibition” (n= 9). Severely apathetic phenotypes were more functionally impaired and had more extensive brain atrophy than those with mild apathy or severe disinhibition alone. Further imaging analyses indicated that the right middle temporal region is critical for the development of disinhibition, an association that remains with disease progression and in the context of severe apathy. Finally, no difference in time to residential care admission was found between phenotypes.

Conclusions: This study reveals that different clinical behavioral phenotypes of bvFTD have differing profiles of functional decline and distinct patterns of associated cortical changes. These findings emphasize the importance of apathy in functional impairment, highlight the role of the right temporal region in disinhibition and suggest that disability may be a sensitive outcome measure for treatments targeting reduction of apathy. These phenotypes could also support understanding of prognosis and clinical management.
Original languageEnglish
Pages (from-to)570-577
Number of pages8
JournalNeurology
Volume89
Issue number6
Early online date12 Jul 2017
DOIs
Publication statusPublished - 8 Aug 2017

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