Apathy and depression are the most common neuropsychiatric symptoms in mild cognitive impairment (MCI) and Alzheimer disease (AD). This study was the first to explore midlife motivational abilities as a predictor of the progression of apathy and depression in MCI and AD. It used a subsample of the Aging, Demographics, and Memory Study (N = 137). Participants, aged over 70, were categorized according to baseline clinical diagnosis (normal cognition, MCI, or AD). Assessments were conducted at an 18-month interval. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. Midlife motivational abilities were estimated on the basis of the main occupation using the Occupational Information Network (O*NET) database, which provides detailed information on worker abilities. Repeated measures analysis of covariance was used. Apathy and depression were found to be particularly high in participants with AD and high motivational abilities. Apathy, but not depression, increased over time in those with AD and high motivational abilities. It would appear that holding on to unattainable goals with strong motivational efforts when faced with severe cognitive loss might lead to unproductive persistence, depressive reaction, and more apathetic behavior.