ASCEND: Aspirin Use Does Not Influence Dementia Risk in Patients with Diabetes

New data from the ASCEND trial demonstrates long-term use of low-dose aspirin did not increase risk of dementia among patients with type 2 diabetes.

Presented at the American Heart Association 2021 Scientific Sessions, data from the study indicate use of low-dose aspirin did not influence the risk of dementia among patients aged 40 years and older with type 2 diabetes and no history of cardiovascular disease, but investigators cautioned further research is needed.

“The results show no clear effect of daily low-dose aspirin on the risk of dementia, with a non-significant 9% proportional reduction in risk. However, the uncertainty around this 9% benefit ranged from a 19% reduction in dementia risk to a 2% increase. This is reassuring that an increase in the risk of dementia is unlikely for the millions of people worldwide who regularly take aspirin to protect against the risk of heart attack and stroke,” said study author, Jane Armitage, FRCP, a professor of clinical trials and epidemiology at the Nuffield Department of Population Health at the University of Oxford in the UK, in a statement. “The results mean a modest benefit of daily low-dose aspirin on risk of dementia is possible, however, we need studies with more people developing dementia to be sure.”

Funded by Alzheimer’s Research UK, Bayer, the British Heart Foundation and the UK Medical Research Council, the ASCEND trial randomized 15,427 patients in the UK with diabetes and without cardiovascular disease or recorded dementia who were followed for a mean of 7.4 years. With results related to primary prevention of cardiovascular disease published in NEJM in 2018, the AHA 2021 analysis was a prespecified secondary analysis of the trial, which examined end points included incidence of broad dementia as well as incidence of vascular and major bleeding events.

The analysis included multiple key outcomes of interest. These included a broad dementia outcome, narrow dementia outcome, and cognitive function z-score at final follow-up. The broad dementia outcome was defined as dementia, cognitive impairment, confusion, use of dementia mediations, and referral to memory clinic or geriatric psychiatry. The narrow dementia outcome only included dementia. Investigators pointed out dementia outcomes were identified via events reported by participants during the trial, use of ICD-10 codes, and other indications of cognitive impairment in follow-up and electronic records.

Among the 15,427 patients included in the study, 1146 participants experienced the broad dementia outcome, including 548 randomized to aspirin and 598 randomized to placebo (RR, 0.91 [95% CI, 0.81-1.02]). The narrow dementia outcome occurred among 537 patients, including 254 randomized to aspirin and 283 randomized to placebo (RR, 0.89 [95% CI, 0.75-1.06]).

In observational analyses, results suggested having a nonfatal vascular event was associated with a more than doubling in risk of experiencing the broad dementia outcome (RR, 2.39 [95% CI, 1.96-2.92]). Additionally, experiencing a major bleeding event was associated with increased risk of experiencing the broad dementia outcome (RR, 1.99 [95% CI, 1.52-2.60]).

“The overall effect of aspirin on dementia and cognitive impairment was uncertain,” Armitage added. “Aspirin may be protective for dementia by preventing some strokes due to blockages, or it may increase the risk because of bleeding into the brain.”

This study, “Effects of Aspirin on Dementia and Cognitive Impairment in the ASCEND Trial,” was presented at AHA 2021.