Supplementary Material for: Association of aspirin with dementia or mild cognitive impairment: A systematic review and meta-analysis of randomized trials

Background: At present, the effect of aspirin in preventing dementia or mild cognitive impairment (MCI) is controversial. Clarifying their association is of interest for subsequent relevant clinical trials. Methods: Four databases (PubMed, Embase, Web of science, and the Cochrane library) were searched from inception to May 12, 2023 for randomized controlled trials (RCTs) that explored the effects between aspirin and dementia or MCI. Two reviewers independently extracted and analyzed data using Stata software. Discrepancy was resolved by a third reviewer. The primary outcomes were dementia and MCI. The secondary outcomes were cognitive decline and changes in cognitive scores. Results: Five RCTs with 46804 participants at randomization were included. For the primary outcomes, low certainty evidence showed that aspirin was not associated with dementia (OR=0.93, 95%CI (0.85, 1.03), P＞0.05, I2=0%) or MCI (OR=1.00, 95%CI (0.88, 1.14), P＞0.05, I2=3.3%). For the secondary outcomes, moderate certainty evidence showed that aspirin was not associated with cognitive decline (OR=1.02, 95%CI (0.93, 1.11), P＞0.05, I2=0%) and a change in global cognitive score (SMD=-0.01, 95%CI (-0.03, 0.02), P＞0.05, I2=0%). Low certainty evidence showed that aspirin was not associated with a change in verbal learning memory score (SMD=-0.04, 95%CI (-0.09, 0.01), P＞0.05; I2=72.5%). Conclusions: Low and moderate certainty evidence showed that aspirin was not associated with dementia, MCI, cognitive decline, or better cognitive scores. Future research may need to focus more on subtypes of dementia, mainly vascular dementia or other vascular neurocognitive diseases, and assess whether aspirin has long-term clinical benefits in a large sample of patients with dementia or MCI