No Benefit of Aspirin in Preventing Dementia    

Sue Hughes            

May 02, 2017

A new review of the literature has found no evidence that low-dose aspirin protects against cognitive decline or dementia.

The review, published online in the Journal of the American Geriatric Society on April 20, was conducted by a team led by Nicola Veronese, MD, Institute of Neurosciences, Italian Research Council, Padova, Italy.

"Neither the longitudinal studies nor the randomized controlled trials included in our meta-analysis suggest a significant benefit of aspirin on reducing cognitive decline or dementia, but they do suggest a significant increase in adverse effects — mainly gastrointestinal issues, so the risk benefit is not going in the right direction," coauthor Brendon Stubbs, PhD, Anglia Ruskin University, Chelmsford, United Kingdom, commented to Medscape Medical News.

"Our bottom-line message is that aspirin should not be used as a preventative strategy to reduce cognitive decline or dementia at the present time. There are other things that people can do which have a more positive risk benefit, such as taking regular exercise and eating healthily."

He added that while people may be taking low-dose aspirin for other indications — prevention of heart disease and certain cancers — the researchers considered only cognitive function in the current review. "So we cannot make any recommendations on other possible uses," he concluded.

However, this is not the end of the story because a large randomized controlled trial of aspirin for the prevention of dementia is underway, which will give far more reliable information on whether aspirin has any benefit for this indication.

In the current paper, the authors explain that low-dose aspirin is often used for the prevention of cardiovascular disease because of its antithrombotic properties. It also has anti-inflammatory properties, and preclinical models suggest that aspirin may decrease neuroinflammation and oxidative stress in the central nervous system, mechanisms that could aid in the prevention of cognitive decline or dementia.

They conducted a systematic review of the literature, looking for studies on low-dose aspirin for preventing cognitive decline or dementia, and identified eight appropriate studies: five longitudinal studies and three randomized, controlled trials.

The five longitudinal studies included 26,159 community-dwelling participants (mean age, 65.1 years; mainly women; followed for a median of 6 years), of whom 3035 (11.6%) used low-dose aspirin. Three studies investigated dementia as an outcome, and the other two considered cognitive impairment.

A meta-analysis of these studies showed that after adjustment for a median of three potential confounders, the use of low-dose aspirin was not significantly associated with onset of dementia or cognitive impairment (five studies: odds ratio, 0.82; 95% confidence interval [CI], 0.55 - 1.22; P = .33).  

When each study was considered separately, only one study, with the largest cohort available (n = 23,915 participants at baseline), reported a significantly lower risk for dementia at follow-up, taking into account four potential confounders.

Although the three studies using dementia as the outcome reported a lower risk (OR, 0.59; 95% CI, 0.33 - 1.05; P = .84) than the two studies that examined cognitive impairment (OR, 0.96; 95% CI, 0.62 -  1.51; P = .66), the interaction between aspirin use and outcome was not significant (P = .18).

In the three randomized controlled trials, which included 10,037 participants, the use of low-dose aspirin was not associated with better global cognitive test scores  (standardized mean difference [SMD], 0.00; 95% CI, –0.04 to 0.05; P = .84).

Two studies reported information regarding verbal memory and executive function and fluency tests. Although no significant differences emerged in terms of verbal memory tests (SMD, –0.02; 95% CI, –0.06 to 0.03; P = .42), the use of low-dose aspirin was associated with slightly better executive function and fluency test results (SMD, 0.06; 95% CI, 0.02 - 0.11; P = .006). This difference was estimated to correspond to a 2.6-year younger age and a 20% lower risk for cognitive decline than with placebo in a single study.

In the three randomized trials, the percentage of participants using low-dose aspirin who completed the studies was lower than the percentage of controls (69.9% vs 75.9%, respectively).

Only two studies (one longitudinal and one randomized) reported information regarding side effects. The prevalence of gastrointestinal adverse events was 10 times higher in people taking aspirin (15.2%) than in controls (1.4%; P < .001).

Noting that the average age of the participants was 65 years, the researchers point out that use of low-dose aspirin at this age may be  "too little, too late," as it is believed that pathologic changes typical of dementia happen 20 years before the clinical symptoms present.

They also note that the observational studies did not use propensity score in their analyses, which is the best method for comparing a population that is taking a drug with another one that is not. Moreover, the possibility of selection bias in longitudinal studies and the fact that a consistent percentage of people not taking aspirin took other nonsteroidal anti-inflammatory drugs might have created another important bias in the results. 

In addition, participants may have been taking low-dose aspirin for the secondary prevention of cardiovascular conditions, so "preexisting comorbidities at baseline may have interfered with potential cognitive beneficial effects of low-dose aspirin and explain the null result."

They also point out that no study included information on APOE ε4 status, which could be a relevant factor in establishing a link between aspirin use and cognitive decline.

More reliable information on the effect of aspirin on cognitive function and prevention of dementia will come from the ASPirin in Reducing Events in the Elderly Study (ASPREE), an ongoing randomized trial including 19,000 healthy participants aged 65 years and older, the largest primary prevention aspirin study ever undertaken in healthy older people.

The authors have disclosed no relevant financial relationships.

J Am Geriatrics Soc . Published online April 20, 2017. Abstract 

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