Neuropsychiatric symptoms (NPS) occur frequently in mild cognitive impairment (MCI) and Alzheimer’s dementia (AD). The authors examined the relationship between NPS and white-matter integrity in these conditions. Twenty-two individuals with MCI and 23 with mild AD underwent clinical assessments including the Neuropsychiatric Inventory Questionnaire and 3.0-tesla magnetic resonance scans. Fractional anisotropy (FA) was measured in the following manually-drawn regions of interest (ROI): fornix, cingulum bundle, splenium, and cerebral peduncles (control region). The probability of having NPS by tertile of ROI FA was assessed by logistic regression. Because associations were similar within MCI and AD groups, the two groups were combined. Compared with those in the highest tertile, participants within the lowest anterior cingulum (AC) FA tertile were more likely to exhibit irritability, agitation, dysphoria, apathy, and nighttime behavioral disturbances. After adjusting for Mini-Mental State Exam status, participants in the lowest versus highest tertile of AC FA were more likely to report irritability. Using DTI, low AC FA was associated with increased odds of irritability in mild AD and MCI participants. Further imaging studies are necessary to elucidate the role of the AC in the pathophysiology of neuropsychiatric symptoms in AD and MCI.