Effects of Aspirin on Dementia and Cognitive Function in Patients With Diabetes

The ASCEND trial examined the effect of daily low-dose aspirin (LDA; 100 mg) in 15,480 diabetic patients aged ≥40 years without known cardiovascular events. They found that, over 7 years, LDA nonsignificantly reduced the incidence of "broad dementia," defined as dementia, cognitive impairment, or confusion, ascertained through self-report or medical records. However, any potential benefit was outweighed by a 29% increased risk of bleeding (gastrointestinal and intracranial). The large size of this randomized trial and length of follow-up are clear strengths. Limitations of ASCEND were the young mean age (63 years) and high education level (62%; >16 years) — both protective against cognitive impairment — and the methods used to define dementia, as it is frequently undetected and underdiagnosed by primary care providers and medical records.

However, the findings of ASCEND align with the results of two recent trials of LDA as a primary preventive agent against dementia. The ARRIVE trial, among European and US primary care patients aged 55 to 60 years with moderate cardiovascular risk but without diabetes, showed no protective effect of LDA against dementia. The ASPREE trial in Australian and US participants (mean age, 72; 9% with diabetes; no prior history of cardiovascular events, dementia, or physical disability) also found no benefit of LDA in preventing cognitive decline or dementia. Taken together, there is no good evidence that LDA is an effective primary prevention agent against cognitive decline or dementia in older persons with or without diabetes, and the high bleeding risk (identified in all three trials) outweighs any small potential protective effect against cardiovascular disease. Importantly, the results of these trials have informed the recent change in the 2021–2022 USPSTF guidelines for primary prevention LDA use. Specifically, it recommends individual decision–making for patients aged 40 to 59 years at increased risk of cardiovascular disease, and discourages LDA use for patients aged ≥60 years.¹ However, it remains unclear whether specific subgroups of individuals could derive any benefit. To address this, the ongoing NIA/NCI–sponsored ASPREE-XT observational follow-up study (reaching completion at 2024) is assessing the legacy effect of LDA in prevention against cognitive decline and dementia and will conduct subgroup analyses including by race/ethnicity and diabetes status.

Reference

1. US Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(16):1577–1584. https://jamanetwork.com/journals/jama/fullarticle/2791399