Alzheimer's disease (AD) is the most common form of senile dementia. As it has become clear that the cause of sporadic AD is likely to be multifactorial, much attention has been devoted to the existing environmental factors that can modulate the manifestation of the disease. Among these influences, anesthesia has come under scrutiny due to potentially serious side-effects, specifically with respect to brain function in the elderly. Some research suggests that anesthesia might enhance the risk of AD. Moreover, anesthetics have recently been demonstrated to enhance AD-like pathology in mouse brain and cell cultures. About 40 millions people receive general anesthesia per year in the USA, and perioperative administration of therapeutic compounds able to prevent or reduce the deleterious effects of anesthetics on the brain is likely to be beneficial. Here, we will investigate the impact of memantine (Forrest Labs), a drug that has been shown to reduce clinical deterioration in moderate to severe AD, on the pathology of AD in mouse models. These proposed studies will provide novel insights into the role of general anesthetics in the neuropathogenesis of AD, and will examine whether memantine can reduce their effects. This will help lay the groundwork and justify future prospective studies in humans.