Aspirin Not Proven to Prevent Dementia and Cognitive Impairment – Results of the ASCEND Trial

Key Points:

• The ASCEND trial sought to determine whether low-dose aspirin could prevent dementia in >15,000 older individuals in the United Kingdom
• The randomized comparison showed that for both the narrow and broad (including delirium, cognitive impairment) dementia definitions there was no significant difference between the aspirin and placebo groups over median 7.4 years of follow-up
• Results excluded proportional harms of >2% and benefits of >19%
• Future studies evaluating whether aspirin might have more modest proportional impacts of 15-18% may be warranted in the future

The utility of aspirin for primary prevention of a host of cerebrovascular conditions is a common focus of research in recent years. Though aspirin reduces the risk of major occlusive vascular events its ingestion comes at the risk of increased bleeding. The potential benefit of the antiplatelet and anti-inflammatory effects is therefore balanced with the feared risk of brain bleeding. Prior studies have not convincingly identified whether aspirin plays a preventative role in cognitive decline. This is particularly important to assess among diabetes patients who have higher risk of vascular events and dementia than normoglycemic individuals.

Jane Armitage, FRCP (Nuffield Department of Population Health at the University of Oxford, U.K.) presented the results of the latest developments from the ASCEND trial (ClinicalTrials.gov NCT00135226) studying the effects of aspirin on dementia and cognitive impairment at the AHA virtual Scientific Sessions in 2021. The ASCEND trial, funded by the British Heart Foundation, was a randomized trial conducted in the UK amongst 15,840 patients 40 years of age or older with any type of diabetes but no prior cardiovascular disease. The effects of aspirin on cardiovascular disease were previously reported in the New England Journal of Medicine in 2018 and showed that aspirin use prevented vascular events but at increased bleeding costs. ASCEND trial participants were randomized to 100-mg aspirin daily or placebo or to 1 gram capsules of omega-3 fatty acids or placebo though the results of the omega-3 portion of the trial were not announced here. Mean follow up was 7.4 years during the trial plus 1.8 years after the trial with 99% linkage to electronic health records (EHR) and >99% follow-up completed for morbidity and mortality. There were no significant differences in baseline demographics between the aspirin and placebo groups.

In order to appropriately identify the effects of aspirin on dementia, there were both narrow and broad definitions of dementia included in the trial. The narrow definition included only dementia itself, whereas the broad definition included cognitive impairment, delirium, use of dementia medications, referral to memory clinic or geriatric psychiatry. Cognitive function was also assessed at the final trial follow up.

Professor Armitage notes in her presentation that observational data showed that future dementia risk is associated with non-fatal vascular events (RR 2.40 [95% CI 1.97-2.92]) and major bleeds (RR 1.96 [95% CI 1.49-2.56]). The randomized data showed that for the broad dementia cohort there was no significant difference between the aspirin and placebo groups (7.1% vs 7.8%, respectively; RR 0.91, 95% CI 0.81-1.02). Amongst the narrowly defined dementia cohort there was similarly no significant difference between the aspirin and placebo groups (3.3% vs 3.7%, respectively; RR 0.89, 95% CI 0.75-1.06). When evaluating the cognitive function testing performed at the end of the study there was a small trend toward improvement with aspirin but no significant difference seen. The trial’s discussant, Amytis Towfighi, MD, FAHA notes that one limitation of the trial is reliance on hospital data through means of an EHR. Future possible investigations on the role of antiplatelet therapies for dementia prevention should consider larger sample sizes, longer follow up, and including antiplatelet medications with more favorable bleeding profiles.