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Vol. 21, No. 5-6, 2006
Issue release date: May 2006
Dement Geriatr Cogn Disord 2006;21:373–379

Orbitofrontal Dysfunction Related to Both Apathy and Disinhibition in Frontotemporal Dementia

Peters F. · Perani D. · Herholz K. · Holthoff V. · Beuthien-Baumann B. · Sorbi S. · Pupi A. · Degueldre C. · Lemaire C. · Collette F. · Salmon E.
aCyclotron Research Center, University of Liège, Liège, Belgium; bVita Salute San Raffaele University, and IRCCS H San Raffaele, IBFM-CNR, Milan, Italy; cDepartment of Neurology, University of Cologne, and Max-Planck Institute for Neurological Research, Cologne, dDepartment of Psychiatry and Psychotherapy, Dresden University of Technology, eDepartment of Nuclear Medicine, Dresden University of Technology, and PET Center, Research Center Rossendorf, Dresden, Germany; fDepartment of Neurological and Psychiatric Sciences, University of Florence, gDepartment of Physiopathology, University of Florence, Florence, Italy

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Orbitofrontal metabolic impairment is characteristic of the frontal variant of frontotemporal dementia (fv-FTD), as are early changes in emotional and social conduct. Two main types of behavioral disturbances have been distinguished in fv-FTD patients: apathetic and disinhibited manifestations. In this study, we searched for relationships between brain metabolism and presence of apathetic or disinhibited behavior. Metabolic activity and behavioral data were collected in 41 fv-FTD patients from European PET centers. A conjunction analysis of the PET data showed an expected impairment of metabolic activity in the anterior cingulate, ventromedial and orbital prefrontal cortex, the dorsolateral prefrontal cortex and the left anterior insula in fv-FTD subjects compared to matched controls. A correlation was observed between disinhibition scores on the Neuropsychiatric Inventory scale and a cluster of voxels located in the posterior orbitofrontal cortex (6, 28, –24). Comparison of brain activity between apathetic and nonapathetic fv-FTD patients from two centers also revealed a specific involvement of the posterior orbitofrontal cortex in apathetic subjects (4, 22, –22). The results confirm that the main cerebral metabolic impairment in fv-FTD patients affects areas specializing in emotional evaluation and demonstrate that decreased orbitofrontal activity is related to both disinhibited and apathetic syndromes in fv-FTD.

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