title: 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.
abstract: 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.
authors.affiliation: 1 Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.|2 Monash Ageing Research Centre (MONARC) Monash University, The Kingston Centre, Cheltenham, Australia.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Ward
authors.affiliation: 3 Monash Biomedical Imaging & ARC Centre of Excellence for Integrative Brain Function, Monash University, Clayton, Australia.
authors.forename: Parnesh
authors.initials: P
authors.lastname: Raniga
authors.affiliation: 3 Monash Biomedical Imaging & ARC Centre of Excellence for Integrative Brain Function, Monash University, Clayton, Australia.|4 Monash Imaging, Monash Health, Clayton, Australia.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Ferris
authors.affiliation: 1 Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Woods
authors.affiliation: 1 Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.|5 Department of Medicine (Neuroscience), Monash University, Melbourne, Australia.
authors.forename: Elsdon
authors.initials: E
authors.lastname: Storey
authors.affiliation: 6 Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bailey
authors.affiliation: 7 Behavioural Neuroscience, Florey Institute for Neuroscience and Mental Health, Melbourne Brain Centre, Heidelberg, Australia.
authors.forename: Amy
authors.initials: A
authors.lastname: Brodtmann
authors.affiliation: 8 Department of Aged Care Services, Austin Health, Heidelberg, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Yates
authors.affiliation: 9 The Florey Institute of Neuroscience and Mental Health, Parkville, Australia.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
authors.affiliation: 1 Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Trevaks
authors.affiliation: 1 Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Rory
authors.initials: R
authors.lastname: Wolfe
authors.affiliation: 3 Monash Biomedical Imaging & ARC Centre of Excellence for Integrative Brain Function, Monash University, Clayton, Australia.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Egan
authors.affiliation: 1 Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: John J
authors.initials: JJ
authors.lastname: McNeil
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000453:epidemiology*; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007391:International Cooperation; D008279:Magnetic Resonance Imaging; D018579:Patient Selection; D018570:Risk Assessment; D018401:Sample Size; D020521:Stroke / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000517:prevention & control*; D066127:White Matter / Q000000981:diagnostic imaging / Q000187:drug effects*
chemical_list: D005343:Fibrinolytic Agents; D001241:Aspirin
keywords: Cerebral microbleeds; aspirin; cognitive decline; dementia; healthy aging; neuroimaging; small vessel disease