Following new evidence suggesting a link between atrial fibrillation and cognitive decline and dementia, Health Europa Quarterly spoke to Professor Ben Freedman of the Heart Research Institute about what this could mean for the future of cardiovascular and dementia-related care.
The rate of dementia and cardiovascular diseases is increasing year on year, generating huge costs for health systems, and heavily impacting the lives of those affected. Now, new evidence has emerged which shows a consistent link between a condition where the heart beats irregularly (atrial fibrillation) and a decline in cognitive abilities and dementia. If such a connection could be validated through further research and clinical trials, it could dramatically inform preventative measures surrounding cardiovascular and neurological care which not only affects older adults but younger generations, too. The paper published earlier this year was collated by AF-Screen International Collaboration and spearheaded by the group’s founder, Professor Ben Freedman. As well as being director of external affairs at the Heart Research Institute, Professor Freedman is also an honorary professor of cardiology at The University of Sydney and former head of the department of cardiology at Concord Hospital. He spoke to Lorna Rothery about his latest Frontiers review regarding the link between atrial fibrillation (AF) and dementia and his continuous endeavours to build on cardiovascular research to improve patient awareness and care.
How much is already known about the link between cardiovascular health and the onset of neurological diseases?
We call stroke a cardiovascular disease as the brain is attached to blood vessels and during a stroke arteries can become blocked so that part of the brain dies, or else a haemorrhage occurs that involves bleeding into, or around, the brain. Many of the major risk factors for stroke are associated with cardiovascular conditions which include hypertension, diabetes, and hypercholesterolemia. We know that by reducing many of these risk factors, we can prevent stroke. Prevention is also much better than trying to treat the effects of stroke after it has happened. However, for those with AF, we also know that if your risk of stroke is high enough, anticoagulants can reduce the stroke risk by about two-thirds. There are not many conditions like this where if the risk is increased, by giving a therapy, you can potentially prevent a major stroke from occurring by two-thirds.
One of the particular aspects of cardiovascular disease that I have been concentrating on for the past 10 years is arrhythmia and atrial fibrillation (AF). The condition itself is not very well known by the general public, nor does it seem particularly threatening to people when you explain that it relates to an irregular heartbeat. Unfortunately, however, atrial fibrillation is common. Once you reach middle age, you have a one in three lifetime chance of developing the condition. Additional risk factors such as high blood pressure, diabetes, or a prior stroke can also make you more susceptible. A strong predictor of dementia is prior stroke but having consistently high blood pressure makes it even more likely to develop dementia later on.
Our paper was published by members of the AF Screen International Collaboration, a group I founded seven years ago, and which now comprises almost 200 people from 38 different countries including cardiologists, general practitioners, geriatricians, stroke specialists, nurses and pharmacists, patient groups, and health economists. Together we published three review papers in Circulation (the main journal of the American Heart Association) covering the need for atrial fibrillation screening and the importance of searching for AF after a stroke.
What is the significance of searching for AF after a stroke has occurred?
Atrial fibrillation is associated with a third of all ischemic strokes, so it is not a rare cause, and it is preventable. Of that 30%, roughly 10% of AF cases are not known at the time of a stroke and in about 20% of cases, the AF was known but either untreated or treated with aspirin which does not prevent stroke effectively in AF. After a stroke, in the absence of AF, the best treatment to prevent a second one is aspirin. While aspirin does not prevent strokes related to atrial fibrillation it can be very helpful for preventing other types of strokes. Searching for AF after a stroke is important.
If you find atrial fibrillation after a stroke, anticoagulation can reduce recurrent strokes, that is why searching for it afterwards is important because it changes therapy from aspirin to anticoagulants. Screening for AF before a stroke in the older population at risk of both AF and stroke would also be hugely beneficial. With atrial fibrillation there are two key considerations: one is adequate therapy for the heart rhythm itself, and the other is focusing on the strokes that occur in atrial fibrillation. Detecting AF is problematic because it is often asymptomatic, especially in older people. That means you need to actively look for it, whether that be through taking a pulse reading or doing a rhythm strip for 30 seconds. AF that is difficult to detect carries the same risk as that which presents symptoms. It is not a benign condition, you can look for it, and if you find it it should be treated to lessen the risk of a stroke. Sometimes AF is paroxysmal – it comes and goes – so it may not be present on a single pulse or ECG check. This may require more intensive screening, though the AF detected may not be as risky as persistent or permanent AF.
Can you explain the connection between AF and dementia?
Here we are talking about vascular brain injury. We often think of dementia alongside Alzheimer’s disease in that you get amyloid and Tau deposits, and treatments are mostly palliative or simply slow down progression. Cognitive decline occurs before the onset of dementia, and what we have reported is something that other people have noted, but ours is a much more comprehensive view that considers whether screening for atrial fibrillation might be effective. We have to tie down the link between AF and dementia to show that it is causative because it could just be an innocent bystander, or it could have shared risk factors.
If there was a signature for the development of dementia that we could look for, and we could give a therapy to treat it, that could be truly game-changing. That is why we have tried to highlight AF as a potential risk factor. There is a lot of research needed because there are lots of potential causes, and this is what our paper has endeavoured to explore. Similarly, until trials are undertaken where you compare people who are on therapy with those who are not, it is very hard to show causation that is reduced by clots. In people with atrial fibrillation, we can see many asymptomatic brain infarctions which could be called silent strokes, and we should be looking at the progression of those and also the progression of both dementia and cognitive decline. There are a couple of trials looking at cognitive decline as an endpoint and that is another thing that we are preaching, we need to look at this as an endpoint because it is an increasingly important endpoint for people.
We know that cases of AF and dementia are increasing year on year, particularly among older adults, should we be looking at the potential risk factors for cognitive decline in younger generations, too?
Cognitive decline can affect the younger generation, it affects older people more because they have additional risk factors including AF and hypertension. Age is one of the most important predictors of atrial fibrillation. However, when we look at cognitive decline, we find that the relationship with atrial fibrillation is stronger in younger people. This entails examining people’s cognitive abilities with a standardised test, which should be done in research though maybe simple tests could be carried out in practice, but it is very hard to introduce this.
There are a couple of studies underway where the primary outcome is reducing cognitive decline, and these do include younger people. Furthermore, younger people with AF usually do not need anticoagulants to prevent stroke. Anticoagulants work in reducing AF-related brain stroke but if we can show that cognitive decline is different in people on anticoagulants who do not need them for stroke prevention then there is a serious possibility of reducing that decline in others.
There is a consistent association between AF and dementia, but we are not sure if it is causal or confounded by the shared risk factors. And some potentially treatable pathophysiologic implications might underpin this risk. We know that continued hypertension, which is a risk factor for both AF and stroke is also a risk factor for dementia so controlling hypertension is crucial for all, but especially if you find AF.
How else would you like to see healthcare systems improve prevention strategies for heart health and dementia?
It is premature because we do not know yet whether prevention of AF will prevent dementia. However, managing the cardiovascular-related risk factors such as weight management, low amounts of alcohol, and controlling hypertension will likely reduce the risk of atrial fibrillation, dementia, and stroke.
It is too early to know whether there is something more specific about atrial fibrillation that we should be looking at, but it is important to keep conducting research in this area because there is so little we can do at present to prevent dementia. We should be investigating cognitive decline in younger people with AF ahead of dementia; that association is stronger in younger people which is worrying.
How do you hope to develop your research moving forward?
First of all, our group is trying to stress the importance of looking for atrial fibrillation, and that is not just feeling the pulse once, but looking more intensively for atrial fibrillation that is paroxysmal and is here one time and not here another. We have instituted an individual patient data meta-analysis of all screening studies and our group comprises all the people who have been part of the big screening studies which is advantageous. We conducted a conventional smaller meta-analysis which we have just submitted to a journal and though it has not yet been published or peer-reviewed, it does suggest that more intensive screening could reduce stroke. When we do the individual patient meta-analysis it will include the ongoing large SAFER study in over 100,000 patients (Screening for Atrial Fibrillation with ECG to Reduce stroke) being run by the University of Cambridge. The HRI will run its only international arm. It will be by far the biggest study on screening, and dementia is one of the endpoints. The combined analysis will give us a much clearer idea of whether a strategy of more intensive systematic screening will prevent stroke.
Trials are ongoing now which look at cognitive decline and brain imaging and whether giving anticoagulants to people with AF, who would not otherwise be prescribed them, affects cognitive decline over a few years. Considering the scale and the price of stroke, it is too big an issue to not investigate the importance of screening for AF, and likewise considering the scale and burden of dementia and cognitive decline it is important that we develop research to help inform prevention strategies and treatments.
Professor Ben Freedman OAM
Director of External Affairs
Heart Research Institute
Group Leader of the Heart Rhythm and Stroke Prevention Group