Background: Neuropsychiatric disturbances are common in mild cognitive impairment (MCI). Depression and apathy may identify a subset of MCI subjects at higher risk of progression to Alzheimer’s disease (AD). However, it remains uncertain whether a broader spectrum of psychopathology is associated with progression to AD. Methods: Fifty-one MCI subjects were assessed for neuropsychiatric symptoms using the Neuropsychiatric Inventory. Subjects were followed for an average of 2 years. Twelve subjects (23.5%) progressed from MCI to possible/probable AD and 39 subjects (76.5%) remained stable or improved. Baseline Neuropsychiatric Inventory indices were compared between groups. Results: Subjects progressing to AD had a significantly higher prevalence of psychopathology than subjects who remained stable or improved (100 vs. 59%). Depression (67 vs. 31%) and apathy (50 vs. 18%) were more common in subjects who were later diagnosed with AD. After statistical adjustments for other baseline demographic variables, these specific symptoms were less robust predictors of progression to AD than the presence of any psychopathology. Conclusions: These findings suggest that neuropsychiatric symptoms in MCI are a predictor of progression to AD. Depression and apathy appear to be most useful for identifying MCI subjects at highest risk of developing dementia.