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

Abstract

Objectives: To investigate the association between long term low-dose acetylsalicylic acid (LDASA) use and the development of all-cause dementia, Alzheimer's 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.

Acute Myocardial Infarction and Risk of Cognitive Impairment and Dementia: A Review

“…A meta-analysis published in May 2022 found that subjects with pre-existing CAD who took low-dose aspirin had significantly lower rates of AD and VD compared to those who did not [ 185 , 186 , 187 ]. However, the use of antiplatelet therapy on cognition has not been studied specifically in the post-AMI population, likely due to the key role of antiplatelet therapy in AMI management.…”

“…There are limited placebo-controlled trials regarding antiplatelet use in VD, as the diagnosis of VD is based on a history of cardiovascular risk factors, stroke or AMI, with patients likely to already be on an antiplatelet. One randomised controlled trial, multiple cohort studies and one systematic review have all concurred that antiplatelet therapy may reduce the risk of VD [ 185 , 187 , 202 ]. A longitudinal study of patients on the South London Stroke Register found that dual antiplatelet therapy (DAPT) significantly reduced rates of cognitive impairment in stroke patients with AF, and another randomised controlled trials reported reduced rates of early neurological deterioration in post-stroke patients on DAPT compared to aspirin alone [ 200 , 203 ].…”