Thursday October 4 2012
Many older people take low-dose aspirin to help prevent blood clots
“An aspirin a day may slow brain decline in elderly women at high risk of cardiovascular disease”, BBC News claims. Frustratingly, while aspirin appears to slow down changes in cognitive ability (such as the ability to remember facts and carry out mental arithmetic), overall “it made no difference to the rate at which women developed dementia”.
This headline is based on research into the association between taking a daily low-dose aspirin and changes in cognition over five years among elderly women. The women were tested at the beginning of the study to assess their mental state and information on their aspirin use was collected. Five years later, the women once again took a test to determine their mental state.
Those on a daily aspirin regimen at the beginning of the study exhibited significantly less cognitive decline than the women who did not regularly take aspirin over the five years. The researchers speculate that this may be due to aspirin improving the flow of blood to the brain.
While levels of cognitive decline were lower, they were still significant, and there was no difference between aspirin users and non-users in terms of risk of developing dementia over five years.
So, while aspirin may have some protective effects, it does not appear to be a ‘magic bullet’ against the development of dementia.
Where did the story come from?
The study was carried out by researchers from the University of Gothenburg and was funded by the Swedish Council for Working Life and Social Research, the Swedish Research Council, The Alzheimer’s Association and the Bank of Sweden Tercentenary Foundation.
The study was published in the peer-reviewed open-access journal, BMJ Open.
This research was covered appropriately by the media, with both the BBC and the Daily Mail reporting that differences were seen in cognitive function, but not in the risk of developing dementia.
Both media outlets also reported on the importance of weighing the potential benefits of daily aspirin against the risks of complications, such as ulcers and stomach bleeds.
What kind of research was this?
This was a prospective cohort study which assessed the association between taking a daily low-dose aspirin and changes in cognitive function over five years, among elderly women.
An observational design such as this can be useful in assessing the relationship between two factors, but cannot tell us whether a daily aspirin regimen directly causes the observed differences in cognitive ability.
The researchers report that the evidence surrounding the relationship between daily aspirin use and dementia is contradictory. Some studies have shown no difference in dementia risk between people who take aspirin and those who don’t. Other studies have shown that aspirin use can actually put people at increased risk of certain types of dementia.
The researchers decided to assess the link between aspirin and noticeable cognitive decline, which they describe as the “earliest sign of dementia”. Experts consider dementia to be a ‘sliding scale’ of cognitive decline, rather than an ‘on-off’ phenomenon.
What did the research involve?
The researchers recruited 681 Swedish women aged between 70 and 92 years. At the beginning of the study, they administered a test commonly used to assess cognitive function, called the mini mental state exam (MMSE).
The MMSE is a 30-point questionnaire assessing a number of cognitive functions, such as:
- mental arithmetic – such as asking people to add consecutive sevens together
- basic language skills – such as asking a person to name certain objects or to spell out the word ‘doctor’ backwards
The higher the MMSE scores, the higher the level of cognitive functioning.
The researchers also collected a range of data on aspirin use and cardiovascular disease risk factors (such as blood pressure, cholesterol levels, diabetes status, smoking status, and age) at the start of the study. They also asked about regular drug use, such as aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen.
The researchers then followed-up five years later, re-administering the cognitive function assessment and once again asking about aspirin use. They then calculated the change in cognitive function scores for each woman over the five-year period.
The researchers also determined how many of the participants had developed dementia over the course of the follow-up period. A diagnosis of dementia was made with a widely-used and well respected ‘symptoms checklist’ (the Diagnostic and Statistical Manual of Mental Disorders, Third Edition or DSM-III-R)
In order to assess the association between aspirin use and cognitive function, the researchers divided the women into two groups:
- those who reported taking aspirin everyday at the beginning of the study
- those who reported no regular aspirin use
They then compared the average change in MMSE score between the two groups. They conducted further subgroup analyses which examined this relationship among:
- women who continued their daily aspirin regimen throughout the entire five years (that is, those who reported daily aspirin use at both the beginning and end of the study) compared to the rest of the participants
- women who were assessed as being at high risk of cardiovascular disease, compared to the rest of the group
Finally, the study authors compared the risk of developing dementia between daily aspirin users and non-users.
What were the basic results?
The study included 681 women, 129 of whom reported daily aspirin use at the beginning of the study. Of the aspirin users, 105 were taking a low-dose (75mg).
Of the aspirin users, 66 continued their daily regimen throughout the study period, 18 used aspirin at the beginning of the study, but not the end. Of those who were not taking aspirin at the start of the study, 67 had started to take it by the end, and 338 never used aspirin regularly.
On average, the MMSE score declined by 0.88 points over the five-year follow-up period for the entire cohort. Among non-aspirin users, this average decline was significant, at 0.95 points, while aspirin users saw an average decline of 0.05 points (significance not reported).
Among the 66 women who continued to take aspirin everyday throughout the five-year study period, cognitive ability was found to increase over the course of the five years, but not significantly so.
There were non-significant declines in cognitive function among the women who reported regular aspirin use at either the beginning or the end of the study, but not for the full five years.
The results of a further subgroup analysis that included 601 women, all of who were at significant risk of cardiovascular disease, due to factors such as high blood pressure or previous history of heart disease were also included.
This analysis found that these women on daily aspirin exhibited significantly less decline in cognitive function over the five year study compared to non-aspirin users (average decline in MMSE score of 0.33 points among aspirin users compared to an average decline of 0.95 points among non-users).
Over the course of the five year follow-up period, seven (8.3%) of the women in the daily aspirin group and 34 (8.4%) in the non-user group, developed dementia. Obviously, this did not represent a significant difference in risk between the two groups.
How did the researchers interpret the results?
The researchers concluded that low-dose aspirin treatment was associated with less cognitive decline in women at high risk of cardiovascular disease.
The results of this study are ambiguous. They suggest that a daily low-dose aspirin regimen may be protective in terms of changes in cognitive functioning among older women. However, they also suggest that aspirin does not protect against the dementia.
The women taking aspirin still experienced cognitive decline, just at a slightly slower rate. The strongest effects in terms of reducing cognitive decline were found in women with a high risk of cardiovascular disease. It is unclear whether the overall protective association seen in the study would apply to women who were not at high risk of cardiovascular disease.
One of the strengths of the study is its prospective nature. By assessing both aspirin use and cognitive function at the beginning of the study, we can be fairly confident that these measures were accurately reported. Had this been a retrospective cohort study, where participants were asked to report their aspirin use over the previous five years, it would be more likely that their status would be incorrectly recorded (especially if they were experiencing memory problems).
The researchers point out that their study has several limitations, including:
- this was an observational study, thus the results may be open to confounding factors such as income, diet, weight and alcohol use
- the MMSE was used to assess cognitive function; while this is a widely used measure, the researchers say it “is not sensitive to detect small changes in cognitive function”. It also does not assess some key domains of cognitive function, which may be more influenced by aspirin use, including executive functioning (such as the ability to plan and think strategically)
- selection bias may have been introduced if participants in the beginning stages of cognitive decline were less likely to use (and continue to use) low-dose aspirin on a daily basis
The researchers suggest that further studies be carried out to verify their findings, especially given the contradictory nature of the evidence around aspirin use and cognition and dementia among the elderly.
They suggest that a randomised control trial would be the most effective way to gather further evidence, but this may be problematic to conduct for ethical reasons (for example, not giving women at high risk of cardiovascular disease a treatment known to reduce that risk).
Overall, this study does not warrant the initiation of a daily aspirin regimen if not otherwise recommended. It is also inadvisable to start taking aspirin without first speaking to your GP, as there can be potentially serious side effects, such as ulcers and an increased risk of bleeding, and the elderly can be most at risk of these effects.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.