Long-term low-dose acetylsalicylic use shows protective potential for the development of both vascular dementia and Alzheimer's disease in patients with coronary heart disease but not in other individuals from the general population: results from two large cohort studies

Objectives: To investigate the association between long term low-dose acetylsalicylic acid (LDASA) use and the development of all-cause dementia, Alzheimer9s disease (AD) and vascular dementia (VD). Design: Meta-analysis of individual participant data from two prospective cohort studies. Setting: Community-dwelling older adults from Germany (ESTHER) and United Kingdom (UK Biobank). Participants: 5,258 ESTHER and 305,394 UK Biobank participants who were 55 years or older and completed drug assessment were included for analysis. Main outcome measures: Cox regression models with inverse probability of treatment weighting to model the underlying cardiovascular risk were used to assess the associations of LDASA use with all-cause dementia, AD and VD incidence. Results: 476 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, 5,584 participants were diagnosed with all-cause dementia, 2,029 with AD and 1,437 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 (HR [95% CI]: 0.96 [0.93 to 0.99]). The strongest protective effect of LDASA 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 LDASA 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 LDASA use. Conclusions: The protective potential of LDASA 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.