Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Network Aging Research, University of Heidelberg, 69115, Heidelberg, Germany.
Alzheimers Res Ther. 2022 May 28;14(1):75. doi: 10.1186/s13195-022-01017-4.
No population-based cohort study investigated a potential inverse association between long-term low-dose acetylsalicylic acid (ASA) use and all-cause dementia and its two most common sub-types Alzheimer's disease (AD) and vascular dementia (VD) so far.
Cox regression models with inverse probability of treatment weighting to model the underlying cardiovascular risk were used to assess the associations of low-dose ASA use with all-cause dementia, AD, and VD incidence in community-dwelling older adults from the German ESTHER study (N = 5258) and the UK Biobank (N = 305,394). Inclusion criteria were age of 55 years or older and completed drug assessment. Meta-analyses of the individual participant data from the two prospective cohort studies were performed.
Four hundred seventy-six cases of all-cause dementia, 157 cases of AD, and 183 cases of VD were diagnosed over a median of 14.3 years of follow-up in ESTHER. In the UK Biobank, 5584 participants were diagnosed with all-cause dementia, 2029 with AD, and 1437 with VD over a median of 11.6 years. The meta-analysis of both cohorts revealed a weak reduction in hazards for all-cause dementia (hazard ratio (HR) [95% confidence interval (CI)]: 0.96 [0.93 to 0.99]). The strongest protective effect of low-dose ASA was observed in participants with coronary heart disease (CHD) in both cohorts, and a significant interaction was detected. In particular, in meta-analysis, a 31% reduction in hazard for AD, 69% for VD and 34% for all-cause dementia were observed (HR [95% CI]: 0.69 [0.59 to 0.80], 0.31 [0.27 to 0.35], 0.46 [0.42 to 0.50], respectively). Furthermore, compared to non-users, users of low-dose ASA for 10 years or longer (who likely use it because they have CHD or a related diagnosis putting them at an increased risk for cardiovascular events) demonstrated a strong protective effect on all dementia outcomes, especially for VD (HR [95% CI]: 0.48 [0.42 to 0.56]) whereas no protective associations were observed with shorter low-dose ASA use.
The protective potential of low-dose ASA for all-cause dementia, AD, and VD seems to strongly depend on pre-existing CHD and the willingness of patients to take it for a minimum of ten years.
目前为止，还没有基于人群的队列研究调查长期低剂量乙酰水杨酸（ASA）使用与全因痴呆及其两个最常见亚型阿尔茨海默病（AD）和血管性痴呆（VD）之间的潜在反比关系。
使用逆概率治疗加权的 Cox 回归模型来建立潜在的心血管风险模型，用于评估德国 ESTHER 研究（N=5258）和英国生物银行（N=305394）中社区居住的老年人中低剂量 ASA 使用与全因痴呆、AD 和 VD 发生率之间的相关性。纳入标准为年龄 55 岁或以上，并完成药物评估。对来自两个前瞻性队列研究的个体参与者数据进行了荟萃分析。
在 ESTHER 的中位 14.3 年随访中，共诊断出 476 例全因痴呆、157 例 AD 和 183 例 VD。在英国生物银行中，中位 11.6 年随访中，5584 名参与者被诊断为全因痴呆，2029 名被诊断为 AD，1437 名被诊断为 VD。两个队列的荟萃分析显示，全因痴呆的危险度略有降低（风险比（HR）[95%置信区间（CI）]：0.96 [0.93 至 0.99]）。在两个队列中，低剂量 ASA 的最强保护作用均观察到在冠心病（CHD）患者中，并且检测到显著的交互作用。特别是在荟萃分析中，AD 的危险度降低了 31%，VD 降低了 69%，全因痴呆降低了 34%（HR [95%CI]：0.69 [0.59 至 0.80]，0.31 [0.27 至 0.35]，0.46 [0.42 至 0.50]）。此外，与非使用者相比，低剂量 ASA 使用 10 年或更长时间的使用者（他们可能因患有 CHD 或相关诊断而增加心血管事件的风险而使用）对所有痴呆结局均表现出很强的保护作用，特别是对 VD（HR [95%CI]：0.48 [0.42 至 0.56]），而使用较短时间的低剂量 ASA 则未观察到保护作用。
低剂量 ASA 对全因痴呆、AD 和 VD 的潜在保护作用似乎强烈依赖于预先存在的 CHD 和患者愿意至少使用 10 年的意愿。
