The Association between the Usage of Non-Steroidal Anti-Inflammatory Drugs and Cognitive Status: Analysis of Longitudinal and Cross-Sectional Studies from the Global Alzheimer's Association Interactive Network and Transcriptomic Data.

The degenerative cognitive and physical decline of Alzheimer patients, coupled with the extensive psychological and economic tolls imposed on family members that serve as caretakers, necessitate the discovery of effective cures and preventative measures for age-related cognitive depreciation. In the journey of Alzheimer's disease treatment discovery, several cross-sectional and longitudinal studies have delineated a noticeable association between the use of nonsteroidal anti-inflammatory drugs (NSAIDs), a class of low-cost drugs with minimal side effects, and the alleviation of age-related memory impairment. In this study, four datasets (two cross-sectional and two longitudinal studies) derived from the Global Alzheimer's Association Interactive Network (GAAIN) were analyzed. The significant association between the usage of NSAIDs and better cognitive status was observed. The results agree with the findings of previous studies that the use of NSAIDs may be beneficial in the early stages of Alzheimer's disease. Transcriptomic data show that ibuprofen treatment results in upregulation of several genes involved in arachidonic acid metabolism including PPARγ, Cyp4a12b, Cyp2c66, and Cyp2c37 in the hippocampus. The increase in conversion of arachidonic acid into anti-inflammatory 16C and 18C dicarboxylic acids as well as epoxyeicosatrienoic acids may play a role in reducing the risk of Alzheimer's disease development.