Effect of anti-inflammatory medications on neuropathological findings in Alzheimer disease

Background: There has been no analysis of brain tissue from longitudinally observed, cognitively tested patients to validate whether anti-inflammatory medications protect against the pathological changes of Alzheimer disease. Objective: To investigate the role of anti-inflammatory medications in alleviating the pathological features of Alzheimer disease. Design and Main Outcome Measures: A 5-year postmortem tissue collection was performed after a case-control study of Alzheimer disease (approximately 90 [30%] of patients died during follow-up, of whom consent for autopsy was obtained in 44 [50%]). Cases were selected on the basis of (1) adequate clinical histories of nonsteroidal anti-inflammatory drug usage, (2) no neuropathological findings other than Alzheimer disease, and (3) no generalized sepsis at death. Variables analyzed included neuropsychological test scores and amount of tissue inflammation and Alzheimer-type pathological changes. Two-way analysis of variance was used to determine whether drug usage significantly affected these variables. Setting: The Centre for Education and Research on Ageing and the Prince of Wales Medical Research Institute, Sydney, Australia. Patients: Twelve patients with Alzheimer disease (5 taking anti-inflammatory drugs) and 10 nondemented controls (3 taking anti-inflammatory drugs) were selected (50% of available sample). Results: OF the patients with Alzheimer disease, antiinflammatory drug users performed better on neuropsychological test scores than did nonusers. However, there were no significant differences in the amount of inflammatory glia, plaques, or tangles in either diagnostic group. Conclusion: Long-term anti-inflammatory medications in patients with Alzheimer disease enhanced cognitive performance but did not alleviate the progression of the pathological changes.