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Apathy and disinhibition in frontotemporal dementia

Insights into their neural correlates

From the Cognitive Neuroscience Section (G.Z., E.D.H., F.K., J.G.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; and Dipartimento di Neuroscienze (G.Z., P.F.N.), Università di Modena e Reggio Emilia, Modena, Italy.

Address correspondence and reprint requests to Dr. Jordan Grafman, Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bldg. 10, Room 7D43, MSC 1440, Bethesda, MD 20892-1440 grafmanj{at}ninds.nih.gov

Background: Aberrant social behavior is a defining symptom of frontotemporal dementia (FTD) and may eventually occur in all syndromes composing the FTD spectrum. Two main behavioral abnormalities have been described: apathy and disinhibition, but their neuroanatomical correlates remain underspecified.

Methods: Sixty-two patients with a clinical diagnosis of FTD participated in the study. Voxel-based morphometry of MRI data was performed to explore the association between gray matter loss and severity of the two behavioral profiles as measured by the Apathy and Disinhibition subscales of the Frontal Systems Behavior Scale.

Results: Compared with a group of controls, the FTD group showed extensive bilateral atrophy predominantly involving frontal and temporal lobes. Within the FTD group, the severity of apathy correlated with atrophy in the right dorsolateral prefrontal cortex. The severity of disinhibition correlated with atrophy in the right nucleus accumbens, right superior temporal sulcus, and right mediotemporal limbic structures.

Conclusions: Prefrontal and temporal regions are differentially associated with apathy and disinhibition. Our results support the view that successful execution of complex social behaviors relies on the integration of social knowledge and executive functions, represented in the prefrontal cortex, and reward attribution and emotional processing, represented in mesolimbic structures.

Abbreviations: ACC = anterior cingulate cortex; BA = Brodmann area; DLPFC = dorsolateral prefrontal cortex; FrSBe = Frontal Systems Behavior Scale; FTD = frontotemporal dementia; FWE = family-wise error; Mattis-DRS = Mattis Dementia Rating Scale; NPI = Neuropsychiatric Inventory; NS = not significant; OFC = orbitofrontal cortex; VBM = voxel-based morphometry.

Supplemental data at www.neurology.org

Supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program (G.Z., E.D.H., F.K., and J.G.) and the Italian Ministry of University and Research (G.Z. and P.F.N.).

Disclosure: The authors report no disclosures.

Received March 17, 2008. Accepted in final form May 23, 2008.

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