Background: Repetitive head trauma is an identified risk factor for Alzheimer’s disease (AD). The violence in wife assault is repetitive and targets the head. This association provides a rationale for studying the relationship between spousal abuse and AD. Design: To preliminarily evaluate the possibility of an increased susceptibility for AD in women subjected to spousal abuse and to identify challenges associated with such a study, we performed a pilot case-control study involving women with AD and compared the incidence of spousal abuse against two control groups. Forty consecutive women with AD referred to a Memory Disorders Clinic were enrolled. Individuals were evaluated at three visits (0, 3, 9 months) and were followed for an additional 12 months to ensure that no other diagnosis emerged. Two control groups were likewise assessed. Results: 17.5% (7/40) of the women (average age 71 years) with AD reported spousal abuse with head trauma. In control group 1, 5.0% (2/40) and in control group 2, 7.5% (3/40) of the women reported spousal abuse with head trauma. Conclusions: The development of AD may be a potential long-term consequence of wife assault. Our study suggests spousal abuse as a possible risk factor for AD, and supports the need for larger studies. However, there are practical challenges associated with the successful execution of such a study.