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J Alzheimers Dis. 2017;60(3):1161-1170. doi: 10.3233/JAD-170348.

Disinhibition in Alzheimer's Disease is Associated with Reduced Right Frontal Pole Cortical Thickness.

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Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, Parkwood Research Institute, London, Canada.
Lawson Health Research Institute, London, Canada.
Frontotemporal Disorders Unit, Department of Neurology, Alzheimer's Disease Research Center, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada.
LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, Canada.
Department of Medicine, Division of Neurology, University of Toronto, Toronto, Canada.


Neuropsychiatric symptoms in Alzheimer's disease are among the most disabling and difficult aspects for caregivers and treating health professionals to manage. Despite the high prevalence of these behaviors, little is known about the factors which lead some patients to develop florid behavioral symptoms while others may progress to severe dementia without such phenomenon. We examined whether regional brain volumes as measured by cortical thickness would predict the presence or absence of disinhibition in patients with Alzheimer's disease. Using data from the ADNI, we identified 758 patients with caregiver ratings on the Neuropsychiatric Inventory and a volumetric MRI scan with cortical thickness measurements completed in FreeSurfer by the UCSF core. Of these, 177 patients were found to have disinhibition. Logistic regression models demonstrated that reduced cortical thickness in the right frontal pole was associated with the presence of disinhibition even when controlling for age, disease severity, total intracranial volume, gender, and APOE genotype. The results are considered in the context of leading models of the functions of frontopolar cortex.


Alzheimer’s disease; disinhibition; frontopolar cortex

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