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. (Am J Geriatr Psychiatry 2011; 19:644-653)