ASPREE-NEURO study protocol: A randomized controlled trial to determine the effect of low-dose aspirin on cerebral microbleeds, white matter hyperintensities, cognition, and stroke in the healthy elderly

Int J Stroke. 2017 Jan;12(1):108-113. doi: 10.1177/1747493016669848. Epub 2016 Sep 24.


Rationale Cerebral microbleeds seen on brain magnetic resonance imaging are markers of small vessel disease, linked to cognitive dysfunction and increased ischemic and hemorrhagic stroke risk. Observational studies suggest that aspirin use may induce cerebral microbleeds, and associated overt intracranial hemorrhage, but this has not been definitively resolved. Aims ASPREE-NEURO will determine the effect of aspirin on cerebral microbleed development over three years in healthy adults aged 70 years and over, participating in the larger 'ASPirin in Reducing Events in the Elderly (ASPREE)' primary prevention study of aspirin. Sample size Five hundred and fifty-nine participants provide 75% power (two-sided p value of 0.05) to determine an average difference of 0.5 cerebral microbleed per person after three years. Methods and design A multi-center, randomized placebo-controlled trial of 100 mg daily aspirin in participants who have brain magnetic resonance imaging at study entry, one and three years after randomization and who undergo cognitive testing at the same time points. Study outcomes The primary outcome is the number of new cerebral microbleeds on magnetic resonance imaging after three years. Secondary outcomes are the number of new cerebral microbleeds after one year, change in volume of white matter hyperintensity, cognitive function, and stroke. Discussion ASPREE-NEURO will resolve whether aspirin affects the presence and number of cerebral microbleeds, their relationship with cognitive performance, and indicate whether consideration of cerebral microbleeds alters the risk-benefit profile of aspirin in primary prevention for older people. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613001313729.

Keywords: Cerebral microbleeds; aspirin; cognitive decline; dementia; healthy aging; neuroimaging; small vessel disease.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Hemorrhage / epidemiology*
  • Cognition / drug effects*
  • Double-Blind Method
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Humans
  • International Cooperation
  • Magnetic Resonance Imaging
  • Patient Selection
  • Risk Assessment
  • Sample Size
  • Stroke / diagnostic imaging
  • Stroke / epidemiology
  • Stroke / prevention & control*
  • White Matter / diagnostic imaging
  • White Matter / drug effects*


  • Fibrinolytic Agents
  • Aspirin

Associated data

  • ANZCTR/ACTRN12613001313729