Aspirin Shows No Effect on Lowering Risk of Dementia

April 1, 2020

Cognitive change over time was similar in both the aspirin and placebo groups.

Joanne Ryan, PhD

Results from the Aspirin in Reducing Events in the Elderly (ASPREE-XT) study demonstrated no evidence that aspirin was effective in reducing the risk of dementia, mild cognitive impairment (MCI), or cognitive decline in healthy older individuals.

Among the 575 adjudicated dementia cases, researchers found no difference in the risk of dementia triggers (hazard ratio [HR], 1.03; 95% CI, 0.91—1.17), probable Alzheimer disease (AD) (HR, 0.96; 95% CI, 0.74–1.24), nor MCI (HR, 1.12; 95% CI, 0.92–1.37) between aspirin and placebo.

Led by Joanne Ryan, PhD, senior research fellow and senior lecturer, School of Publish Health and Preventative Medicine, Monash University, ASPREE-XT was a post-treatment, longitudinal observational follow-up study of ASPREE participants that began its follow-up phase in January 2018. The double-blind, placebo controlled original trial of low-dose aspirin included community-dwelling individuals aged >70 years (US minorities >65 years) who were free of cardiovascular disease, physical disability, and diagnosed dementia, with a life expectancy of at least 5 more years.

The study pulled a total of 19,114 participants, randomized 1:1 to 100-mg aspirin to test the effect of daily aspirin versus placebo over 5 years on the prespecified secondary outcomes of incident dementia and MCI overall, and in prespecified subgroups.

Following baseline and Year 1 assessment, cognitive outcome measures were then conducted biennially over the follow-up period (Year 3, Year 5 and Year 7 or close-out visit in 2017). Assessments such as the Modified Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test-Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT) were used to examine cognition.

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Dementia triggers, or individuals with suspected diagnosis of dementia, were defined as a MMSE score <78, or a drop of more than 10.15 points from the predicted score based on their own baseline MMSE and after adjustment for age and education. Additionally, those who reported memory concerns or cognitive problems or were prescribed cholinesterase inhibitors were considered triggers as well.

Of the 19,114 participants, 488 in the aspirin group reached the dementia trigger criteria (11.6 per 1000 person-years) compared with 476 participants (11.3 per 1000 person-years) in the placebo group (HR, 1.03; 95% CI, 0.91—1.17).

In the aspirin group, rate of incident dementia was 6.7 events per 1000 person-years, compared to 6.9 events per 1000 person years in placebo. Additionally, researchers saw similar rates of reported memory problems (4.4 and 4.6 per 1000 person-years, respectively), MMSE scores <78 (4.1 and 4.3 per 1000 person-years, respectively), >10-point drops in predicted MMSE from baseline (1.5 and 1.7 per 1000 person-years, respectively), and patients prescribed a cholinesterase inhibitor (1.0 and 0.7 per 1000 person-years, respectively) in both the aspirin and placebo groups.

In addition to the similar incident dementia and probable AD figures, aspirin did not prolong disability-free survival (HR, 1.01; 95% CI, 0.92—1.11).

The rates of MCI and cognitive decline remained similar over time as well. In the aspirin group, 838 participants (26.5 per 1000 person-years) were defined as having cognitive decline, compared with 816 participants (25.6 per 1000 person-years) in the placebo group (HR, 1.04; 95% CI, 0.94—1.14). There was no significant change to indicate that the average trajectory of cognitive function would change over time using aspirin when compared with placebo.

“This study provides no evidence that low-dose aspirin initiated in relatively healthy older adults is effective in preventing dementia, clinically probable AD, or MCI, or in reducing cognitive decline during active treatment over a median 4.7 years. This conclusion was consistent across a series of participant subgroups. The potential longer-term legacy effects of aspirin on these outcomes will be assessed with ongoing follow-up of the participants,” the Ryan and colleagues concluded.

REFERENCE

Ryan J, Storey E, Murray AM, et al. Randomized placebo-controlled trial of the effects of aspirin on dementia and cognitive decline. Neurology. Published online March 25, 2020. Accessed March 31, 2020. doi: 10.1212/WNL0000000000009277