In a recent article, we reported that researchers at Amsterdam University Medical Center, Netherlands have conducted an enormous retrospective study of Dutch people with high blood pressure to investigate how common antihypertensives affect a person’s risk of developing dementia.
Here at Medical News Bulletin, we love to give our readers an inside view of ongoing research. We were fortunate that Dr Jakob Schroevers, corresponding author of the research took some time to give us a bit more of the story behind the science.
MNB: What was the problem you were looking to solve?
Dr JL Schroevers: Dementia poses a significant public health challenge. With increasing life expectancy, particularly in low- and middle-income countries, a rise in dementia cases is expected in the coming decades.
Despite ongoing efforts, there’s still no cure for dementia, and any potential cure is likely to be very expensive, making its accessibility in poorer areas problematic. However, addressing certain risks can lower dementia risk.
One of these attributable risk factors is elevated blood pressure (BP), also called hypertension. Elevated BP damages blood vessels, including those in the brain, leading to oxygen deprivation, and subsequent damage to the brain tissue surrounding it, sometimes unnoticed. This damage to brain tissue may contribute to various forms of dementia, including Alzheimer’s disease. Treating elevated BP has been shown to lower dementia risk, with some types of BP-lowering medications potentially reducing dementia risk more than others. If confirmed, preferring certain types of BP-lowering medication over otherwise equivalent other types could provide a cheap and safe strategy to lower dementia risk globally.
MNB: Were you surprised by any of the results?
JLS: Our findings are consistent with some previous studies that identified differences between types of BP-lowering medications. The consistent link between angiotensin receptor blockers (ARBs) with lower dementia risk compared to angiotensin-converting enzyme (ACE) inhibitors is particularly intriguing. This is because both these types of BP-lowering medication are commonly prescribed to similar patient groups with high BP, including those who additionally have diabetes.
MNB: What did you do differently that made this study an improvement?
JLS: In this study, we improved upon previous efforts in several ways. Firstly, we analysed anonymised routine-care data originating from general practitioners (GP) electronic health records. This way we had access to a very large population of community-dwelling individuals, enabling us to detect even subtle differences in risk and draw conclusions applicable to a wider audience, thus enhancing the reliability of our findings. Secondly, we had access to many years of data per patient, which was crucial given the slow development of dementia; this allowed us to observe differences in dementia risk associated with different types of BP-lowering medications over time. Lastly, to address the issue of changing medications, we utilised real-time prescription data from over 8 million prescriptions belonging to more than 130 thousand individual patients, ensuring that any medication changes during the study period were appropriately accounted for in our risk calculations.
MNB: Why would a doctor typically prescribe ACEi instead of the other types? Is it preference? habit? does it depend on what type of hypertension?
Although several BP-treatment guidelines state that various types of BP-lowering medications are equivalent treatment options for hypertension without comorbidities, it is possible that this is perceived differently by doctors. For instance, ACE inhibitors have been available to doctors for a longer time than ARB. On the other hand, ARBs have lesser side effects, compared to ACE inhibitors. Therefore, perhaps doctors are more comfortable to prescribe certain types of medications, compared to others. Furthermore, certain underlying health conditions, including diabetes or heart attack, may influence doctors’ decisions when prescribing certain medications. This could result in patients receiving ACE inhibitors might having inherently higher dementia risk than those receiving ARBs, regardless of the medication type itself, but because of the underlying condition. Despite attempts to account for these factors in our study by considering patient characteristics, these kinds of obfuscation can never be entirely eliminated in observational studies like ours. Therefore, despite our findings suggesting associations between medication types and dementia risk, other types of studies are necessary to confirm these differences.
MNB: What do you hope will happen next?
JLS: What we hope for next is an experiment study, known as a randomised controlled trial (RCT), to be conducted to rule out confounding. In such a trial, participants would be randomly assigned to receive for instance either ACE inhibitors or ARBs, allowing for a more definitive assessment of the effects of these medications on dementia risk. If the results of our study are replicated in such a trial, it could lead to changes in BP-treatment guidelines, favouring ARBs over ACE inhibitors. However, conducting such a trial will be challenging due to its long duration, the large number of participants required, and consequently high costs. Despite these challenges, it’s an important step that could have significant implications for dementia prevention in the long term.
MNB: Do you have anything you would like to tell our readers?
JLS: BP-lowering drugs reduce dementia risk in patients with elevated BP, certain types potentially more effectively than others. However, further research is needed to confirm these differences beforeBP-treatment guidelines may be changed. Meanwhile, while there is no cure for dementia yet, adopting a healthy lifestyle, including a balanced diet, maintaining a healthy weight, and managing blood pressure, can lower the risk of various diseases, including dementia, empowering individuals to take control of their health.
