Stress, PTSD, and dementia.

The physiological consequences of acute and chronic stress on a range of organ systems have been well documented after the pioneering work of Hans Selye more than 70 years ago. More recently, an association between exposure to stressful life events and the development of later-life cognitive dysfunction has been proposed. Several plausible neurohormonal pathways and genetic mechanisms exist to support such an association. However, many logistical and methodological barriers must be overcome before a defined causal linkage can be firmly established. Here the authors review recent studies of the long-term cognitive consequences of exposures to cumulative ordinary life stressors as well as extraordinary traumatic events leading to posttraumatic stress disorder. Suggestive effects have been demonstrated for the role of life stress in general, and posttraumatic stress disorder in particular, on a range of negative cognitive outcomes, including worse than normal changes with aging, Alzheimer's disease, and vascular dementia. However, given the magnitude of the issue, well-controlled studies are relatively few in number, and the effects they have revealed are modest in size. Moreover, the effects have typically only been demonstrated on a selective subset of measures and outcomes. Potentially confounding factors abound and complicate causal relationships despite efforts to contain them. More well-controlled, carefully executed longitudinal studies are needed to confirm the apparent association between stress and dementia, clarify causal relationships, develop reliable antemortem markers, and delineate distinct patterns of risk in subsets of individuals.