An Aspirin A Day Does Not Keep Dementia At Bay

A large study published online on March 25, 2020, in Neurology®, the medical journal of the American Academy of Neurology, revealed that taking low-dose aspirin once a day does not reduce the risk of thinking and memory problems caused by mild cognitive impairment or probable Alzheimer’s disease, nor does it slow the rate of cognitive decline.

Aspirin or acetylsalicylic acid (ASA) is a drug used to reduce pain, fever, or inflammation. Wikipedia lists many uses of this popular drug: aspirin given shortly after a heart attack decreases the risk of death;  it  is used as a  long-term medicine to help prevent further heart attacks, ischemic strokes, and blood clots in people at high risk; aspirin  may also decrease the risk of certain types of cancer, particularly colorectal cancer.

Aspirin thins the blood. For long, doctors have been prescribing low-dose aspirin for some people to reduce their risk of heart disease and stroke. Of late, there were also considerations of possible risks such as bleeding in the brain due to taking aspirin leading to the need to obtain guidance from a doctor before continuing with aspirin.

Is Aspirin beneficial to the brain?

“Because aspirin can be beneficial to the heart, researchers have hypothesized, and smaller previous studies have suggested, that it may also be beneficial to the brain, possibly reducing  the risk of dementia by reducing inflammation, minimizing small clots or by preventing the narrowing of blood vessels within the brain,” a press release from the American Academy of Neurology said

“Worldwide, an estimated 50 million people have some form of dementia, a number that is expected to grow as the population increases, so the scientific community is eager to find a low-cost treatment that may reduce a person’s risk,” study author Joanne Ryan, PhD, of Monash University’s School of Public Health in Melbourne, Australia noted.

 “Unfortunately, our large study found that a daily low-dose aspirin provided no benefit to study participants at either preventing dementia or slowing cognitive decline,” she added

The Study deign

ASPREE or Aspirin in Reducing Events in the Elderly   was a double-blind, placebo-controlled trial of low-dose aspirin. Initially, the researchers identified   between March 2010 and December 2014, healthy community-dwelling individuals aged 70 years and over through partnership with >2,000 general practitioners (GPs) in Australia and in the United States through clinic-based mailing lists, electronic medical screening, and media advertisements.  

For African American and Hispanic patients in the United States, the age limit was lowered to 65 years and over due to their higher risk of disease. Both groups were free of cardiovascular disease, physical disability, and diagnosed dementia. Researchers sent letters inviting them to participate in eligibility screening. Eligibility criteria included being free from cardiovascular disease and physical disability and being expected to survive for at least 5 years. Individuals with a self-report or physician diagnosis of dementia at recruitment, or with a Modified Mini-Mental State Examination (3MS) 10 score of less than 78, were also ineligible.

Totally, 19,114 participants with 9,525 randomized to aspirin and 9,589 to placebo participated in the study. They ranged in age from 65 to 98 years, and 87.4% were recruited in Australia. They did not identify significant differences in baseline characteristics between participants randomized to aspirin and placebo, including health factors and cognitive performance that may predispose them to cognitive impairment.

They underwent a battery of tests: the Modified Mini-Mental State Examination, Hopkins Verbal Learning Test–Revised, Symbol Digit Modalities Test, and Controlled Oral Word Association Test. They took these thinking and memory tests at the start of the study as well as during follow-up visits.

The investigators followed them for an average of 4.7 years, with annual in-person examinations. Over the course of the study, 575 people developed dementia.

Results

Researchers found no difference between those who took aspirin and those who took placebo in the risk of developing mild cognitive impairment, dementia, or probable Alzheimer’s disease. There was also no difference in the rate of cognitive change over time. 

The study was to run for five years. However, the sponsors the National Institute of Aging and others stopped the double-blind treatment phase of the trial, 6 months early on June 12, 2017, because of futility for the primary composite outcome of disability-free survival (survival free from persistent physical disability, dementia, or death).

“ASPREE was the first prospectively planned placebo controlled trial of aspirin therapy undertaken among individuals aged predominantly 70 years and over, among whom the risk of cognitive decline is greater and where an effective intervention could have the largest net benefit. 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”, the study concluded.

The results were disappointing for the researchers. For them, their study is not yet over. They consider it was work in progress

 “… it is possible that the length of just under five years for our study was not long enough to show possible benefits from aspirin, so we will continue to examine its potential longer-term effects by following up with study participants in the coming years,” Joanne Ryan clarified.