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.背景：目前，阿司匹林在预防痴呆或轻度认知障碍（mild cognitive impairment, MCI）方面的效果尚存争议。明确二者的关联对于后续相关临床试验具有重要研究价值。 方法：本研究检索了建库至2023年5月12日的4个数据库，即PubMed、Embase、Web of Science及Cochrane图书馆，筛选旨在探讨阿司匹林与痴呆或轻度认知障碍关联效应的随机对照试验（randomized controlled trial, RCT）。由2名评价者独立提取数据，并采用Stata软件进行统计分析，研究分歧由第三名评价者协调解决。本研究的主要结局指标为痴呆与轻度认知障碍，次要结局指标为认知衰退及认知评分变化。 结果：最终纳入5项随机对照试验，共纳入46804名随机化参与者。针对主要结局指标，低确定性证据显示，阿司匹林与痴呆（比值比（odds ratio, OR）=0.93，95%置信区间（confidence interval, CI）：0.85~1.03，P＞0.05，I²=0%）或轻度认知障碍（OR=1.00，95%CI：0.88~1.14，P＞0.05，I²=3.3%）无显著关联。针对次要结局指标，中等确定性证据显示，阿司匹林与认知衰退（OR=1.02，95%CI：0.93~1.11，P＞0.05，I²=0%）及整体认知评分变化（标准化均数差（standardized mean difference, SMD）=-0.01，95%CI：-0.03~0.02，P＞0.05，I²=0%）无显著关联；低确定性证据显示，阿司匹林与言语学习记忆评分变化无显著关联（SMD=-0.04，95%CI：-0.09~0.01，P＞0.05，I²=72.5%）。 结论：基于低、中等确定性证据，阿司匹林与痴呆、轻度认知障碍、认知衰退或认知评分改善均无显著关联。未来研究可更多聚焦于痴呆亚型，主要为血管性痴呆或其他血管性神经认知疾病，并在大样本痴呆或轻度认知障碍患者中评估阿司匹林的长期临床获益。