Low-Dose Aspirin Protection Against Cognitive Decline? Think Again

BOSTON, April 27 -- Low-dose aspirin doesn't protect women against overall cognitive decline, a finding that adds to doubts about whether anti-inflammatory drugs offer any neuroprotective benefit.

Among more than 6,000 healthy women who took low-dose aspirin or placebo for a decade, there were no significant between-group differences in overall cognitive function, rate of cognitive decline, or risk for serious decline, reported Jae Hee Kang, Sc.D., of Brigham and Women's Hospital here, and colleagues.

"In this study, we observed no apparent benefit of low-dose aspirin in slowing cognitive decline over four years," the authors wrote online in BMJ. "Other methods for preserving cognitive function in older people need to be investigated."

Women who took aspirin had a 20% lower risk for decline in category fluency, the authors noted, but the effect seen with this secondary endpoint was not enough to tip the scales in aspirin's favor.

Earlier this week, two other NSAIDs were shown to offer no protective benefit against Alzheimer's, investigators reported online in Neurology. Neither naproxen (Aleve) nor celecoxib (Celebrex) reduced the risk of developing Alzheimer's, at least in the short term, found researchers in the ADAPT (Alzheimer's Disease Anti-inflammatory Prevention Trial) study

According to results of the randomized ADAPT study funded by the National Institute on Aging, there was even a suggestion that both naproxen and celecoxib were associated with a slightly increased risk of dementia.

Interest in the use of NSAIDs for Alzheimer's prevention was sparked by a study, published in Neurology in 1993, indicating that indomethacin in doses of 100 to 150 mg/day appeared to protect mild-to-moderately impaired Alzheimer's patients from the degree of cognitive decline exhibited by well-matched controls.

But results from randomized trials conducted since have been inconclusive or have shown no neuroprotective benefit for the NSAIDs rofecoxib, naproxen, nimesulide, and diclofenac, the ADAPT investigators noted.

In the current study, Dr. Kang and colleagues looked at data from the Women's Health Study, a randomized, double-blind, placebo controlled two-by-two factorial trial of aspirin given in doses of 100 mg on alternate days, and supplementation with vitamin E 600 IU on alternate days. The goal of the trial was to determine whether the combination could protect women against cardiovascular disease and cancer.

The cohort included 6,377 women, mean age 72, from both arms of the study. The women had three cognitive assessments conducted by telephone interview at two-year intervals. They were tested for general cognition, verbal memory, and category fluency.

The primary study outcome was a global cognition score calculated by averaging performance across all tests. The investigators also looked at verbal memory scores, calculated by averaging the performance of volunteers on four measures.

They found that at the first assessment, an average of 5.6 years after randomization, the cognitive performance among women treated with aspirin was similar to that of placebo-treated controls. The mean difference in global score was -0.01 (95% confidence interval, -0.04 to 0.02).

There was also no significant difference between the groups in the mean decline in global score from the first cognitive assessment to the last, with a mean difference of 0.01 (95% CI, -0.02 to 0.04).

The risk that women would be in the highest (worst) 10th percentile of cognitive decline was likewise similar between the aspirin and placebo groups (relative risk 0.92, 95% CI, 0.77 to 1.10), and there were no significant differences in verbal memory scores.

However, women who took aspirin had a slightly lower risk of decline in category fluency, measured by asking the participants to name as many animals as they could in one minute. The relative risk for decline in this measure for aspirin takers versus controls was 0.80 (95% CI, 0.67 to 0.97).

"Because the category fluency test partially assesses executive function -- a cognitive system that is influenced by vascular disease -- it is biologically plausible that low dose aspirin may specifically help preserve executive function," the authors wrote. "However, because category fluency was the only test in our battery that measured executive function, and because this was not a primary outcome of our trial, this result should be interpreted with caution and confirmed by future studies."

Dr. Kang and colleagues noted that their study was limited by the age of the cohort, which was relatively young compared with the total study cohort of women 65 and older, and may have contributed to their failure to see a major cognitive decline over the follow-up period. They also noted that they were unable to measure cognitive decline from randomization, but pointed out that risk factors for cognitive decline were evenly distributed at baseline.