Friday July 26 2013
ACE inhibitors relax the blood vessels, lowering blood pressure
"Blood pressure drugs may boost brainpower," the Daily Mail reports and "may slow the onset of Alzheimer's".
The paper reports on a study of a class of drugs called angiotensin-converting enzyme (ACE) inhibitors, which help lower blood pressure by relaxing the walls of the blood vessels.
The researchers were interested in whether certain types of ACE inhibitors slowed mental decline in patients diagnosed with the most common forms of dementia.
The study found that, over a six-month period, patients taking the drugs had slightly slower rates of mental decline than those who were not taking them. It also found that the mental ability of patients who were newly prescribed this type of ACE inhibitor improved slightly after six months compared with those already taking the drugs and those not taking them.
This study suggests that ACE inhibitors may slow down the rate of mental decline in some dementia patients and may improve the mental scores of some patients during the first six months of treatment.
However, this was a very short and small study and it is not clear if the small differences in speed of decline would have long-term clinical implications.
It is also unclear whether the slowing in mental decline is a previously unrecognised effect of ACE inhibitors or just a by-product of better controlled blood pressure.
Large high-quality studies are required to confirm whether these drugs can help dementia patients and, if so, which patients they may benefit.
Where did the story come from?
The study was carried out by researchers from University College Cork and Mercy University Hospital, both in Ireland, and McMaster University, Canada. It was funded by an organisation called Atlantic Philanthropies, the Health Services Executive Ireland, the Irish Hospice Foundation and the Canadian Institutes of Health Research.
The study was published in the peer-reviewed open access medical journal BMJ Open.
The Daily Mail and The Independent implied in their first few paragraphs that all ACE inhibitors might slow the rate of mental decline. This is incorrect as the study only looked at a type called centrally acting ACE inhibitors (CACE-Is). CACE-Is cross the blood–brain barrier so they have a potential effect on blood flow and blood pressure inside the brain.
Both the Mail and The Independent included helpful comments on the study from independent experts.
The Mail also included the authors’ caveat that ACE inhibitors may be harmful to some patients.
It is also important to point out that ACE inhibitors can cause unpredictable effects if taken with other medications, including some that can be bought over the counter. Check with your GP or pharmacist before taking anything in combination with this medication.
What kind of research was this?
This was a case control study that compared the rates of mental decline between dementia patients taking CACE-Is and patients not taking CACE-Is. A second comparison was made between patients newly prescribed the drugs, those already taking the drugs and those not taking them at all.
This type of study cannot show for certain that CACE-Is slow the rate of mental decline in dementia patients, it can only highlight possible trends. A randomised controlled trial is the best way of examining the effect of a particular intervention.
The researchers point out that there is growing evidence that blood pressure lowering drugs, particularly CACE-Is, which cross the blood–brain barrier, are associated with a reduced rate of mental decline in dementia.
What did the research involve?
For their study, researchers used data collected on 1,749 patients by two memory clinics in Canada between 1999 and 2010.
The data included information on:
- blood pressure
- use of medications
The data also included the scores of two standard screening tests for mental ability:
- the Standardised Mini-Mental State Examination (SMMSE)
- the Quick Mild Cognitive Impairment (Qmci) screen
Researchers say the latter is a new screening test, thought to be more sensitive than the SMMSE. It has six subtests covering five areas:
- working memory – the ability to hold information and facts inside the mind on a short-term basis
- verbal fluency – the ability to recall and use a wide range of different words
- visuospatial ability – the ability to make sense of and use visual information, such as reading a map
- episodic memory – the ability to recall events from the past, both delayed (long-term memories) and immediate recall (short-term memories)
Between 1999 and 2010 the mental ability of each patient was assessed using either of these tests, on two separate occasions, six months apart.
From this database, the study included 817 patients who had been diagnosed with one of three types of dementia:
- Alzheimer’s disease (the most common form of dementia, in which the exact cause is unknown)
- vascular dementia (caused by reduced blood flow to the brain)
- mixed dementia (in which both factors are involved)
They excluded patients with other forms of dementia, mild cognitive impairment, normal mental ability and depression.
After patients for whom test results were not available were excluded, 361 were included for analysis. Eighty-five of the patients were taking a CACE-Is and 276 were not.
They looked at the patients’ scores on the two scales and compared the average rate of mental decline between the two groups. Among those taking CACE-Is, researchers also looked at the results for 30 patients who had been newly started on the drugs (those within the first six months of treatment).
What were the basic results?
- Researchers found a statistically significant difference in the average six-month rate of decline in Qmci scores between patients taking the drugs (1.8 points) and those who were not (2.1 points).
- Similar differences were seen with the SMMSE test, but these were not significant.
- Among patients in the first six months of CACE-Is treatment, average SMMSE scores improved by 1.2 points, compared with a 0.8 point decline for the patients already taking the drugs and a 1 point decline for those not taking the drugs.
- An analysis, controlling for multiple baseline characteristics, showed significant differences in the rates of decline, in SMMSE, between the three groups.
How did the researchers interpret the results?
The researchers say that, among patients with dementia, mental ability scores may improve in the first six months after CACE-Is treatment and the use of the drugs is associated with a reduced rate of mental decline in patients with dementia. They say this is the first study to demonstrate that mental ability scores improve in patients with dementia starting on CACE-Is, compared with those already having treatment.
This large study has shown an association between centrally acting ACE-inhibitor drugs and slightly slower rates of mental decline in patients with certain forms of dementia.
It has also suggested an association with improved mental ability in dementia patients, during the first six months of taking these drugs.
However, this type of study cannot conclusively prove that drugs help dementia symptoms or improve mental ability in dementia patients. Only a large, high-quality randomised controlled trial would be able to demonstrate what effect these drugs have on mental ability.
It is also uncertain whether the slightly slower rates of mental decline associated with CACE-Is and the improvements in mental ability seen in the first six months translated into significant outcomes, such as affecting patients’ symptoms, behaviour and their ability to carry out day-to-day activities, such as washing and dressing themselves.
The study also has several limitations. As the authors point out, it was conducted in a real world setting where patients who were prescribed the drugs may have had different characteristics from those who weren’t. This means the results could be biased.
Also, very limited numbers of patients from the database were included in the analysis, because, for many, the results of mental ability tests were not available at baseline and six months. It is possible the results would have differed had the data been more complete.
It is important to stress the authors’ message that recent evidence suggests that ACE inhibitors may potentially accelerate certain forms of dementia. This implies that even if they are found to be beneficial in some dementia cases, not all patients will necessarily benefit.
Never take ACE inhibitors if you have not been prescribed the medication by your GP or the doctor in charge of your care.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.