Context: The hallmark pathological changes in Alzheimer disease ( AD) are abundant plaque and tangle formation, especially in the temporal lobes and hippocampus. Although there is increasing evidence that major depression may interact with neuropathological processes in AD, there have been no studies of neuropathological changes in AD as a function of history of major depression. Objective: To test the hypothesis that neuritic plaques and neurofibrillary tangles are more pronounced in the hippocampus of patients with AD with a lifetime history of major depressive disorder, as compared with patients with AD without depression history. Design: Postmortem study. Setting: Nursing home. Participants: The brains of 52 patients with AD without a lifetime history of major depression were compared with the brains of 50 patients with AD with a lifetime history of major depression. Main Outcome Measures: Neuropathological ratings from the Consortium to Establish a Registry in Alzheimer Disease battery. Results: Brains of patients with AD with a lifetime history of depression showed higher levels of both plaque (P <. 005) and tangle (P <. 002) formation within the hippocampus than brains of patients with AD without a history of depression. Post hoc analyses showed that patients with AD who had a history of depression exhibited more rapid cognitive decline than patients without a history of depression (P <. 004). Furthermore, within the group of patients with AD with a history of depression, patients who exhibited concurrent depression at the time of first diagnosis of AD exhibited more pronounced neuropathological changes in the hippocampus (P <. 006). Conclusions: In AD, the presence of a lifetime history of depression corresponds to increases in AD-related neuropathological changes within the hippocampus. These changes go along with more rapid cognitive decline in patients with AD with a history of depression, and are more pronounced in patients with AD suffering from depression early on in the disease process, suggesting an interaction between major depression and AD neuropathology.
