Effects of Aspirin on Dementia and Cognitive Function in Diabetic Patients

THE ASCEND Trial

Sarah Parish; Marion Mafham; Alison Offer; Jill Barton; Karl Wallendszus; William Stevens; Georgina Buck; Richard Haynes; Rory Collins; Louise Bowman; Jane Armitage

Disclosures

Eur Heart J. 2022;43(21):2010-2019. 

In This Article

Abstract and Introduction

Abstract

Aims: Aspirin is widely used in cardiovascular disease prevention but is also associated with an increased risk of bleeding. The net effect of aspirin on dementia and cognitive impairment is uncertain.

Methods and Results: In the ASCEND trial, 15 480 people from the UK with diabetes and no history of cardiovascular disease were randomized to aspirin 100 mg daily or matching placebo for a mean of 7.4 years. The 15 427 ASCEND participants with no recorded dementia prior to baseline were included in this cognitive study with a primary pre-specified outcome of 'broad dementia', comprising dementia, cognitive impairment, or confusion. This was ascertained through participant, carer, or general practitioner report or hospital admission diagnosis, by 31 March 2019 (~2 years beyond the scheduled treatment period). The broad dementia outcome occurred in a similar percentage of participants in the aspirin group and placebo group: 548 participants (7.1%) vs. 598 (7.8%), rate ratio 0.91 [95% confidence interval (CI), 0.81–1.02]. Thus, the CI excluded proportional hazards of >2% and proportional benefits of >19%.

Conclusion: Aspirin does not have a large proportional effect on the risk of dementia. Trials or meta-analyses with larger total numbers of incident dementia cases to increase statistical power are needed to assess whether any modest proportional 10–15% benefits of 5–7 years of aspirin use on dementia exist.

Clinical Trial Registration: Current Controlled Trials number, ISRCTN60635500; ClinicalTrials.gov number: NCT00135226.

Structured Graphical Abstract: The effect of aspirin on dementia in the ASCEND trial: Study design and summary results.

Introduction

In primary cardiovascular disease prevention, daily low-dose aspirin has been shown, in a recent meta-analysis of randomized trials, to cause an 11% proportional decrease in the risk of major vascular events (including a 19% reduction in ischaemic strokes) but a 43% proportional increase in the risk of serious bleeding.[1] Cerebrovascular events are associated with cognitive impairment, and thus, aspirin may prevent cognitive impairment through the avoidance of ischaemic strokes, transient ischaemic attacks (TIAs), and microinfarcts, but could cause cognitive impairment through an increased risk of intracranial haemorrhage and cerebral microbleeds.[2–6] Despite being in widespread use for cardiovascular prevention, it is not known whether aspirin has a net benefit or hazard on dementia and cognitive function. Previous randomized trials of aspirin have not convincingly detected any effect of aspirin use on dementia incidence or cognitive impairment, but this has only been assessed in studies with fewer than 600 dementia cases.[7–9]

Diabetes increases the rate of cognitive decline and risk of dementia and so any effect of aspirin on dementia may be more marked and important among people with diabetes.[10,11] This report, among the 15 427 participants with diabetes but without prior reported dementia or cognitive impairment who had been randomized in the ASCEND (A Study of Cardiovascular Events in Diabetes) trial, assesses the effect of randomization to daily low-dose aspirin for an average of 7.4 years on risk of dementia and other indicators of cognitive impairment. Additionally, we report the observational associations of different types of non-fatal vascular and bleeding events occurring during the trial with subsequent dementia risk.

processing....