An aspirin a day does not keep dementia away. Nor does it hedge the risk of mild cognitive impairment or slow decline, according to results published March 25 in Neurology. Reasoning that the anti-inflammatory and cardiovascular health benefits of low-dose aspirin might confer protection against dementia, the Aspirin in Reducing Events in Elderly (ASPREE) study evaluated the effect of the drug on dementia, Alzheimer’s disease, and cognitive performance in nearly 20,000 people 70 and older. Over an average of five years, the study, led by Joanne Ryan and Elsdon Storey at Monash University in Melbourne, Australia, found no benefits for any endpoint. The findings mesh with previous studies that found no benefit of anti-inflammatory drugs on dementia.
- The 20,000-participant ASPREE trial reported negative results.
- Low-dose aspirin did not reduce MCI or dementia risk.
- It did not change the rate of cognitive decline.
“We would have greatly preferred to have seen benefits from aspirin,” wrote David Knopman and Ronald Petersen of the Mayo Clinic in Rochester, Minnesota in an accompanying editorial. Neither were involved in the study. “But the ASPREE trial results have public health significance nonetheless in that we can conclude that aspirin therapy offers no protective effects for later-life cognition, cardiovascular disease, disability, or death.”
Inflammation is intimately linked with AD. Even so, there is scant evidence that taking common anti-inflammatory drugs—including non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen—wards off dementia (Alzheimer's Disease Anti-inflammatory Prevention Trial Research Group, 2013; Apr 2019 news). As both an anti-inflammatory and an anti-platelet compound used to prevent cardiovascular disease, aspirin could potentially quell inflammation tied to AD and also stem vascular dementia. To test these ideas, the ASPREE prevention trial began in 2010.
The largest prevention study of its kind, it enrolled 19,911 participants who lived in communities in Australia and the United States. Participants were at least 70 years old, and free of cardiovascular disease or cognitive impairment at baseline. Half were randomized to placebo; half to 100 mg aspirin daily. They were followed for an average of 4.7 years, when the study was halted after failing a futility analysis. It predicted the treatment did not increase disability-free lifespan based on a composite of death, dementia, or persistent physical disability. Nor did it reduce all-cause dementia (McNeil et al., 2018).
The new paper includes analysis of additional secondary outcomes from the trial. The authors saw no difference between placebo and aspirin groups in the number of dementia diagnoses, or the type of dementia people developed. The same was true for mild cognitive impairment (MCI): Similar numbers of people were diagnosed with MCI during follow-up, and a similar proportion were designated as MCI due to AD in both groups. The researchers also measured cognitive decline based on performance on a battery of cognitive tests taken at baseline and once every two years during follow-up. Aspirin had no effect.
While these results seem unequivocal, there were some limitations. The study did not enroll participants with cardiovascular disease, who may have stood to benefit the most from treatment, Knopman and Petersen noted. “Because the favorable consequences of aspirin have been seen mainly in individuals with symptomatic cardiovascular disease or cerebrovascular disease, perhaps it was the low burden of pathology in asymptomatic ASPREE participants that led to the null result with aspirin,” they wrote.
The study does not rule out the possibility that starting aspirin in middle age—when the Alzheimer’s cascade begins—could slow the disease, the authors wrote.—Jessica Shugart
- Alzheimer's Disease Anti-inflammatory Prevention Trial Research Group. Results of a follow-up study to the randomized Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT). Alzheimers Dement. 2013 Nov;9(6):714-23. Epub 2013 Apr 3 PubMed.
- McNeil JJ, Woods RL, Nelson MR, Reid CM, Kirpach B, Wolfe R, Storey E, Shah RC, Lockery JE, Tonkin AM, Newman AB, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Donnan GA, Gibbs P, Johnston CI, Ryan J, Radziszewska B, Grimm R, Murray AM, ASPREE Investigator Group. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. N Engl J Med. 2018 Oct 18;379(16):1499-1508. Epub 2018 Sep 16 PubMed.
- Ryan J, Storey E, Murray AM, Woods RL, Wolfe R, Reid CM, Nelson MR, Chong TT, Williamson JD, Ward SA, Lockery JE, Orchard SG, Trevaks R, Kirpach B, Newman AB, Ernst ME, McNeil JJ, Shah RC, ASPREE Investigator Group. Randomized placebo-controlled trial of the effects of aspirin on dementia and cognitive decline. Neurology. 2020 Jul 21;95(3):e320-e331. Epub 2020 Mar 25 PubMed.