Microstructural Alteration of the Anterior Cingulum is Associated With Apathy in Alzheimer Disease

Objectives: To identify regional alterations of white matter integrity associated with apathy in Alzheimer disease (AD). Design: Cross-sectional study. Setting: University Dementia Clinic. Participants: Fifty-one very mild or mild probable AD subjects. Intervention: Volumetric magnetic resonance imaging with diffusion tensor imaging. Measurements: Volume of interest analyses were performed to compare regional fractional anisotropy (FA) between apathy and apathy-free group, and to test linear relationship between regional FA and apathy severity. Apathy was assessed by the Neuropsychiatric Inventory. Results: Apathy group showed significantly lower FA values than apathy-free group in the left anterior cingulum (A-C), regardless of concomitant depression and psychotropic medications. Left A-C FA values also had significant linear relationship with apathy-composite scores as a measure of apathy severity, even after controlling gray matter density of the ipsilateral anterior cingulate cortex. Conclusions: Our findings support that communication failure between the anterior cingulate cortex and other brain structures via the A-C contributes to the development and aggravation of apathy in AD, additionally supporting the general notion of disconnection syndrome for clinical manifestation of AD. To identify regional alterations of white matter integrity associated with apathy in Alzheimer disease (AD). Cross-sectional study. University Dementia Clinic. Fifty-one very mild or mild probable AD subjects. Volumetric magnetic resonance imaging with diffusion tensor imaging. Volume of interest analyses were performed to compare regional fractional anisotropy (FA) between apathy and apathy-free group, and to test linear relationship between regional FA and apathy severity. Apathy was assessed by the Neuropsychiatric Inventory. Apathy group showed significantly lower FA values than apathy-free group in the left anterior cingulum (A-C), regardless of concomitant depression and psychotropic medications. Left A-C FA values also had significant linear relationship with apathy-composite scores as a measure of apathy severity, even after controlling gray matter density of the ipsilateral anterior cingulate cortex. Our findings support that communication failure between the anterior cingulate cortex and other brain structures via the A-C contributes to the development and aggravation of apathy in AD, additionally supporting the general notion of disconnection syndrome for clinical manifestation of AD.