Taking Brain Health to Heart

Henry R. Black, MD; Philip B. Gorelick, MD, MPH


April 11, 2016

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Editor's Note:
Henry R. Black, MD, interviews Philip B. Gorelick, MD, MPH, professor of translational science and molecular medicine at Michigan State University, on the relationship between cognitive health and blood pressure and other cardiovascular risk factors.

Dr Black: Hi. I am Dr Henry Black. I am an adjunct professor of medicine at the New York University (NYU) Langone School of Medicine, and I am here today with my friend and former colleague, Dr Phil Gorelick. Phil, thanks for joining us.

Dr Gorelick: Thank you, Henry. It is a pleasure and honor to be here with you today to talk about this important topic. I am professor of translational science and molecular medicine at Michigan State University and medical director of the Mercy Health Hauenstein Neuroscience Center in Grand Rapids.

Dr Black: You have always been my go-to guy when it came to neurologic issues, especially as they are related to heart disease. When we worked together at Rush University Medical Center, it was always a pleasure to know you were there. What is new? What do you think now is the relationship now between Alzheimer disease and cognitive dysfunction with blood pressure and other cardiovascular risk factors?

Dr Gorelick: This is a really exciting story. We started out in the 1980s with a very restrictive definition of Alzheimer disease. We talked about neurodegeneration, senile plaques. and neurofibrillary tangles in the brain. The definition was set originally by the McKhann criteria group[1] to demonstrate that any systemic disease that might explain the cognitive impairment was not Alzheimer disease.

We began to think in a way that I call "bucket" thinking. We begin to classify cases by disease type: Here is the bucket for Alzheimer disease, here is the bucket for vascular dementia, and so. The two main causes of dementia were very much separated from each other at that time.

Things have changed dramatically, in part because of some of the studies we did in Chicago. What we have learned is that people who have high blood pressure, diabetes, heart disease, and other cardiovascular risk factors can have Alzheimer disease. In fact, in a very nice systematic analysis by Ivan Casserly and Eric Topol that was published in Lancet in 2004,[2] it was shown that the same risk factors for atherosclerosis were risk factors for Alzheimer disease. These were all of the typical risk factors: high blood pressure, diabetes, hypercholesterolemia, physical inactivity, obesity and so on.

Disentangling Alzheimer Disease From Cerebrovascular Disease

Dr Black: Does it make any difference clinically which diagnosis you carry?

Dr Gorelick: What is interesting is that most of the cases of cognitive impairment or dementia that occur in the elderly turn out to be mixed cases. It has been estimated that some 60%-90% of Alzheimer disease patients have cerebrovascular disease.[3] So this gives us a potentially big target for treatment or prevention. We know we can prevent strokes and heart attacks, and high blood pressure is one of the most important of the preventive factors.

And now the question being posed is: Can we also prevent Alzheimer disease? This becomes more controversial. You will recall [this] from the clinical trial world in 1998, when Forette and colleagues[4] published the Syst-Eur trial with the long-acting calcium-channel blocker nitrendipine, and showed that not only could vascular dementia be reduced with blood pressure treatment, but also the risk for Alzheimer disease could be reduced. This began to set into motion a lot of thoughts and ideas about potentially preventing or delaying Alzheimer disease. This was an important paper.

Dr Black: Are there any diagnostic criteria that you would use to separate the two? Do you really need to have plaques in this supravascular circulation or in the brain itself, or can you make that diagnosis on a clinical basis? And does it make any difference if you do?

Dr Gorelick: Again, oftentimes there is concomitance. Cerebrovascular disease, which can cause cognitive impairment, and Alzheimer disease often times coexist. Therefore, it may be difficult to disentangle the two processes.

I have come to think of cognitively impairing processes of later life a little bit differently. I have shifted my thought curve to an "upstream" approach: Let's focus on midlife when we start witnessing vascular risk factors becoming prevalent. I think we should be looking earlier in life—and consider conducting prevention trials, though they would be difficult, because you would have to go for 20 years or more.

My focus or emphasis is controlling blood pressure starting in midlife. There are a number of observational studies that have suggested just that—one of them being the Honolulu-Asia Aging Study,[5] which was very strong in this area. That research suggested that controlling blood pressure earlier in life—in midlife—reduces the risk for cognitive impairment later in life.

Now, neither the clinical trials nor the observational studies have been totally consistent. Studies have shown trends going in different directions. It's not totally clear in terms of what to do, but I think there is a lot of belief it is going to be very important to intervene on blood pressure during midlife.

SPRINT and FINGER trials: Reaching the Public

Dr Black: I couldn't agree more. I think the SPRINT study[6] and others have shown that aggressive treatment of blood pressure that can begin earlier in life than we used to think may give good results. To be less aggressive with hypertension was never a good idea. I am not sure exactly why anybody thought we ought to do that. But in fact that has been overturned very clearly and convincingly by SPRINT.

Is there anything in the wind right now, therapy-wise? How do we get people who are 50 or 60 years old to be focused on their blood pressure and their cholesterol and their exercise? I don't know how to do that. I am not sure whether you do.

Dr Gorelick: Well, we have got some exciting news from a trial called FINGER—a recently published Finnish study,[7] which showed that a multimodal approach of exercise and blood pressure control and other cardiovascular risk factor control can be effective for reducing cognitive impairment.

What I am hoping is that we are going to be able to eventually say to patients that not only can we reduce your risk for heart attack and stroke, but at some point in the not-too-distant future, we are going to be able to say that we are able to reduce the risk for cognitive impairment. This will be a welcome boost to further our blood pressure control campaigns. I can't think of anything more important in the practice of medicine than to get blood pressure under control, but you and I are biased because we work in the area.

Dr Black: Some of it has to do with crafting a message that is digestible, simple, and can be accomplished. There are a lot of things that people will buy into without any evidence at all, and we have many studies that show the value of controlling blood pressure. Whether it is to 140 or 130 mm Hg or less than that is not important. It shouldn't be 150 mm Hg. It shouldn't be 160 mm Hg. It shouldn't be ignored, and I think that is where we should be heading.

Dr Gorelick: Let me address the very important things that you just mentioned. We have three statements that came out recently along those lines. The Institute of Medicine report came out and stated for the first time: Be physically active [and] control your cardiovascular risk factors, including blood pressure, because it may be important for your cognitive or brain health.[8]

The Alzheimer's Association has picked up on this, and now they are saying there are 10 ways to love your brain, and a number of those 10 factors are the same cardiovascular control factors to which the Institute of Medicine refers.[9]

Finally, we have the World Stroke Day Proclamation, which was authored by Vladimir Hachinski.[10] The World Stroke Day Proclamation indicates that we should be more aggressively controlling these risk factors in people who have had transient ischemic attack or stroke, with the idea that we can prevent forms of cognitive impairment.[11]

Dr Black: [When people talk] about heart attacks, they say, "Oh, I will die quietly in bed. That will be fine." But what frightens people more is cognitive decline. Maybe we can capture their interest by telling them that [with better blood pressure control], we may be able to reduce, delay or eliminate [cognitive decline].

I think that is a message we have to send out to health-conscious people, who sometimes try the craziest things and [avoid the] simplest steps.

Are there new drug therapies?

Counting on Cardiovascular Control

Dr Gorelick: What we have found is that about 50% of Alzheimer disease is explained by cardiovascular risk factors. There have got to be important lessons there.

In terms of newer therapies, the pipeline has not been very rich. We have been counting on cardiovascular risk factor control. When there is cerebrovascular disease, we are looking at more novel ways to combine agents. As I mentioned, we are looking at multimodal therapies, such as the FINGER trial. That is where that story rests right now.

But I think just doing the basics [is important]. We know from the Honolulu-Asia Aging Study that if you don't have high blood pressure, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia and if you are better educated, you are going to have a very high chance of living a long, healthful life without cognitive impairment or physical dysfunction. Your instrumental activities of daily living and your ability to get around will remain good. I refer to this as a "fountain of youth" profile.

The problem is that only about 5%-10% of the population fit the profile of no risk factors. So what we are doing now is falling back and saying: Let's control the cardiovascular risk factors, see what happens, and see if we can make a slow-down or prevent in the cognitive impairment as we age.

Dr Black: And be sure you look both ways when you cross the street.

Dr Gorelick: Absolutely.

Dr Black: You didn't mention smoking. I think that is one of the things that is interesting to me, and we have to be patient. It took 25 years from the Surgeon General's report[12] to actually see the rate of smoking decline beginning in 1988. So we have to be patient. We have to keep saying the same things over and over again until people start to listen. I think when they do, we will have to start dealing with another problem: the retirement age. How long should you work, and what should you do?

Dr Gorelick: This is a problem the Japanese are facing right now. They have been so successful in terms of improving longevity that now they have a large population of elders. How are we going to handle this from a policy standpoint? The Japanese health ministry is looking for novel strategies. They are striving to be the super-aging generation and lead the way, by looking at social determinants, housing, and other nontraditional ways to help the elderly population. We believe that it can be done, and they are working on the problem right now. From a policy standpoint, an excess of elderly individuals has become a challenge to a society and may be viewed as an unintended consequence of good health.

Dr Black: Phil, thank you very much. I always enjoy talking with you and working with you. Let's hope we can keep doing it as we get elderly.

Dr Gorelick: It is a pleasure, Henry, and good health.


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