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Alzheimer's and exercise

It's relatively easy to determine whether a person has dementia. But it's not always easy to determine what kind of dementia a person has.

It's common to have a little bit of uncertainty. That's been a problem in our field. It's a problem with our diagnostic technology. It's a problem with the diagnostic criteria that we use. And it's probably a conceptual problem. For instance, it's not absolutely clear that you can draw a bright line between say, stroke-related dementia and Alzheimer's disease, because it appears increasingly likely the two processes may overlap in multiple levels. So it may be to some extent sort of a false distinction.

Is Alzheimer's what we used to call senility?

Possibly. The term "Alzheimer's" has been around for about a century. It's named for Alois Alzheimer, who was a physician who worked in Germany and published a series of case reports about people with memory loss. His original case report actually was about a woman in her 50s. So the term "Alzheimer's disease" was originally given to people with a form of dementia that strikes relatively early in life.

So when I was in medical school, that was the terminology we used. We had early-onset dementia, which was Alzheimer's disease, and then we had senile dementia, or senility, which was considered to be some other process either related to the aging process itself or related to atherosclerosis, but not well characterized.

In the 1970s and `80s, it became apparent that the majority of people with dementia have the same underlying brain process, whether it starts in the 50s or 60s, which is rare, or it starts in the 70s or 80s, which is more common. The term was reinvented. The term "Alzheimer's disease" has a more general application now than it did a generation ago.

So when somebody says, "Why do we hear so much more about Alzheimer's today than we used to?" I think there are two reasons. One is because we have so many more old people who are in the risk group, and there are more cases of dementia by far than we ever had before. And the other is that we use the term in a different way than we used it in the past. It's a term that has been reinvented and will probably have to be reinvented again because our understanding of the disease will inevitably cause us to define our method of diagnosing it and where we draw the lines around it.

Almost everybody as they get older either becomes more forgetful or a little quirky in some respect. How do you draw that line? How can you tell whether there's a more serious underlying problem?

It is normal to have a certain amount of memory impairment with the aging process. This doesn't necessarily start when you're elderly. It's much younger than that — people have a little more difficulty coming up with names. That's probably the first and most common thing. It happens to me every day.

If the memory impairment reaches a point where it interferes with a person's ability to do their normal activities, that is by definition a dementia. A person who had a decline to the point that they couldn't function alone, couldn't take care of themselves: That would be a dementia.

Dementia is usually triggered by some disease of the central nervous system, like Alzheimer's disease or stroke or some similar problem. Most cases of dementia are incurable, but not all of them. Rarely we encounter a person who has some medical problem, some metabolic problem that can be cured. Unfortunately, that's not common. But it happens on rare occasions.

Increasingly, we realize it's probably in most cases a gradual process that has a long silent period. That is the illness or illnesses probably begin middle age, unfold silently, and don't manifest themselves until later in life. In that way, it's much like hypertension, atherosclerosis, diabetes, similar conditions, which have a long period of evolution before clinical symptoms begin. In fact, all of those things may play a role in dementia, including Alzheimer's disease. Increasingly, it's clear that brain disorders like Alzheimer's aren't self-contained illnesses. They have to be seen in the context of a person's overall brain health and overall somatic health, and also their life history and their life habits, which play a role also.

What kind of habits?

Things like exercise. That's probably pretty close to the top of the list. Body weight.

Tell us about that.

If you consider this: Think about a person with a healthy brain that's functioning properly and they're physically fit, they're socially engaged. They're intellectually engaged. The brain, as it turns out, is much more of a plastic organ than we ever believed. I was taught in school that the brain was pretty static. By the time you were 16, 18, it was fixed, and it wasn't going to change very much. That turned out to be absolutely untrue. The brain is constantly remolding itself according to the needs that are presented to it. So if you learn how to play the piano, or learn how to ride a bicycle, there are physical changes in your brain that reflect that. So the brain is constantly remodeling itself. It's influenced by your life experience, and the brain's ability to do that is influenced by its health and by the health of the organ systems that support it.

So say hypothetically you have a predisposition to Alzheimer's disease, which means certain abnormal proteins are being deposited in your brain, probably starting in your 50s. And the symptoms begin with short-term memory impairment when you're in your late 60s or early 70s.

Let's say you're a very physically fit individual. Your brain has a lot of ability to compensate. In that case, your symptoms may not be manifest until maybe five or six years later in life. And since you're talking about a late-life disorder, you may begin to push it back to the point where it's much less of an issue for the bulk of your lifetime. In other words, delaying the onset of symptoms is a very important part of understanding the disease and also presents a treatment opportunity.

For instance, it may not be possible to cure Alzheimer's disease. But it may be possible to alter its manifestation in some way that you push back the age of onset. If you do that, that's the next best thing to a cure. And that's probably the more manageable goal.

So what does physical activity do?

I don't think we really understand all that physical activity does. But one thing, people who are physically active are less likely to develop type-2 diabetes, and that is a significant risk factor. Hypertension is a risk factor. Body weight, especially the people that have body weight around their mid-section, which is also a risk factor for heart disease, is clearly a risk factor for Alzheimer's disease also.

So can you talk to two 50-year-olds who seem healthy and exhibit no signs of Alzheimer's and decide that one is more vulnerable to the disease than the other?

Our technology does not allow us to do that now, but we know that's true because if one of those persons dies of something else and they have an autopsy, we'll find plaques and tangles, the hallmarks of Alzheimer's disease, in a small percentage of those people, just as we'll find atherosclerotic plaques in the arteries of those people who have never had a stroke or a heart attack or other signs of arterial disease, and yet we know it's present. It's a process that unfolds over a period of time. And brain disease appears to be like that as well. The brain has a huge capacity to adapt and cope and compensate.

So you can't tell one of these 50-year-olds, "You shape up and be careful."

I can tell them that if they have a family history of Alzheimer's. Genetics are not destiny here, because not every person with a family history will get Alzheimer's disease. Some people will. The risk is higher. And if you know you have a family history, it makes sense to take that into consideration. We know that these things, the same basic factors that might predispose to stroke or heart disease also increase the risk of Alzheimer's disease. We also know beyond that that people that have engaged minds — that is that they continue to learn, not just practice things that they already know, but to take on new challenges late in life — that kind of brain stimulation also tends to be protective against Alzheimer's disease.

When you say "late in life," what do you mean?

We're shooting at a moving target. We don't have an absolute number. If you take the number 65, that's just an artificial number that was made up by the Social Security Administration in the Roosevelt era. There's no biological point that you can say that there's a threshold.

We change gradually every day of our lives, even kids. The cells are being broken down; they're being replaced. As we get older, that process is less efficient. But there's not a threshold where you can say, "This is when late in life begins."

So I'm really talking about the aging process, really beginning in midlife. The choices we make in our 40s and 50s probably have more of an impact on what happens to us when we're in our 80s than the choices we make at that moment. If you take an 80-year-old and treat their high cholesterol and high blood sugar, it's probably not going to have that much impact on what happens to them for the remainder of their life. If you take a 50-year-old, it could have a really big impact.

We hear about people doing crossword puzzles or learning to play chess because they think it will help them somehow. Is there something specific about those particular activities?

I don't know that we have a scientific answer to that question. We do know from observational studies that if you take people who are continuously mentally active, that take on new challenges into late life, those people tend to do well. People who fail to do those things tend to do poorly.

Breaking that down to the point of saying it's this particular thing — it's the crossword puzzles or the chess or the word play: I think you could make a case that those things are useful. I think you could also say that the people that do those things are concerned. They probably do lots of other things that are also useful. And part of the difficulty with research in aging is that people almost always come in packages. It's not just one thing, but lots of things going on. Someone who's doing crossword puzzles is probably also engaged in other activities that would be helpful to them.

What we're talking about here are the odds. If a person comes to my office with Alzheimer's and their family members are in tow, and the kids say, "Is there anything I can do to improve my odds?" the answer is yes, there are some things that tend to improve your odds.

If a person were to say, "Can you give me a magic bullet here that's going to absolutely prevent me from getting Alzheimer's?" the answer is no. Alzheimer's strikes all social groups, all educational groups, all ethnic groups, so there isn't anybody who is completely sheltered from it.

But we know people with higher educations, higher IQs are less likely to get it. We also know — there was just a study about this — that highly intelligent people are so good at compensating for the disease process that when the symptoms finally begin, they tend to be precipitous. They tend to have a very steep slope of decline, where a person with less intellectual ability would not have been able to compensate to begin with, and those symptoms would have been more evident earlier.

So what we're really talking about here is if you think about Alzheimer's disease as we observe it in a living person, we gauge the person's symptoms — their memory symptoms, their functional ability, sometimes changes in their behavior — things we can observe. We can't look inside the living brain very well to see these plaques and tangles. The plaques and tangles are the pathological hallmarks of Alzheimer's disease.

Probably what happens is the plaques and tangles can happen to anybody, to some extent at random, and some elements are probably influenced by genetics. But whether those plaques and tangles will manifest themselves overtly with memory symptoms or observable changes in thinking and mood and behavior have to do with other things that will mitigate, either tend to push the person toward the direction of developing symptoms at an earlier age or not toward developing symptoms at an earlier age.

You also have to look at survivorship. Let's say a person had a strong genetic predisposition for Alzheimer's disease, and they have lots of plaques and tangles in their brain but they die of lung cancer at age 70. In other words, that's a diagnosis that will never be made. And we have that problem when we fill in genograms, when we're doing genetic research with Alzheimer's disease. It's a late life disorder. You go back several generations: People didn't live as long. Their lifespan was shorter. We don't have good medical records. The concepts of disease were different. So we have trouble plugging in all the holes.

There's a controversial book that came out six months or so ago called The Myth of Alzheimer's Disease that tackles this point. That is, to some extent our diagnosis is based on how long people live, whether they live long enough to show the symptoms. Because a lot more people are going to show the symptoms if they live longer, and it sort of challenges the disease concept. It injects the idea that if we all live long enough, sooner or later we probably will all get it.

Of course we all know people with Alzheimer's. Some we know have elderly siblings who show no sign of the disease.

That's another piece of the puzzle with Alzheimer's. We can divide Alzheimer's into two sub-groups: the early onset, and those are people that have symptoms before age 65. In those cases, genetics seems to play a larger role. The late onset type probably is not controlled by any single gene. Instead what we have are risk factors genes that will push us toward the disorder. They also protect us from the disorder.

So any given person has a constellation of different genetic influences, different lifestyle factors and different lifespan. And all those factors together will finally calculate who ends up getting the disorder and who doesn't.

So much illness is blamed on smoking. Does smoking play a role with Alzheimer's?

A very good question. Smoking increases risk for atherosclerosis and other cardiovascular diseases, and people who smoke have a higher incidence of dementia, both stroke-related dementia and Alzheimer's disease. But there is an idea out there that smoking might protect you from Alzheimer's, and I hear this all the time because there's been some speculation that nicotine may have some value.

Nicotine sharpens mental focus. Some studies suggest it may improve memory in the short run. One of the drugs used to treat Alzheimer's disease: Some of its function is similar to nicotine.

So nicotine as a chemical may actually have some promise in development of treatments for Alzheimer's, but smoking — the tar and all the other things that come along with cigarettes — clearly is a risk factor for Alzheimer's disease.

What about diet? Do some diets pose higher risks?

The same diets that would push us toward cardiovascular disease probably also would push us towards Alzheimer's disease. So high fat, high saturated fat, high glycemic index and concentrated sweets — all those things we know are risk factors for heart disease and stroke are likely risk factors for Alzheimer's also.

There's an interesting ongoing study that's been going on for 20 years, looking at African Americans in Indianapolis and looking at Africans in Nigeria — West Africans that are not genetically dissimilar from African Americans. Lots of things separate the two groups. But Alzheimer's disease and other forms of dementia are more common by far in African Americans than they are in West Africans, even if you make allowances for lifespan. What are the differences? Lifestyle and stress, hypertension, diabetes, obesity, diet. So it's not that Alzheimer's disease doesn't occur, but the frequency is much higher here.

Are some people just going to get it, no matter what?

There's no question, especially people with the early onset type. Some of those people have a genetic predisposition so great that it can't really be overcome.

But I think the people with the late onset type, it may be possible for us, as we refine these concepts, to have active treatments, medications or lifestyle changes that can push back the age of onset. And that would be a useful goal.

Do you have an idea of what percentage of the population gets Alzheimer's?

We have a general idea. Alzheimer's is a relatively common disorder. If you look at dementia, about 10 percent of the people in the United States over the age of 65 have some form or dementia, and about two-thirds of those probably have Alzheimer's disease. There are probably somewhere in the range of 5 million people in the United States with Alzheimer's today, 7,000 to 10,000 in the Louisville area, probably 60,000 or 70,000 in Kentucky. We expect those numbers to roughly double in the next generation, largely because of the increased population of elders.

Are you assuming there will be no progress in preventing it?

I don't think we're going to have enough progress in such a short timeline that we can make a really big difference. We need to be prepared for what the Alzheimer's Association has described as an epidemic. It will really challenge our society, because we will have an increasing number of dependent older people without necessarily the resources at hand to manage all those people.

Is drinking a factor?

There is a form of dementia that's related to drinking. There is what's called alcoholic dementia.

Wet brain.

That's a term that's been used sometimes. Our thinking about alcohol-related dementia has changed. There was a notion that alcoholic dementia was caused by a deficiency in thiamine. Now we recognize that alcohol itself is a brain toxin and can be a cause of cognitive impairment and dementia, whether a person is deficient in thiamine or not.

When people have either a long history of heavy drinking or episodes of heavy drinking they may develop cognitive impairment. If they stop drinking, it's difficult to know what will happen. Some people will have a remarkable improvement. The wet brain dries out.

But they don't have Alzheimer's.

Only if they have it by coincidence. These are common problems. They sometimes overlap. But alcohol does not seem to be a risk factor per se for Alzheimer's.

Small amounts of alcohol, particularly red wine, some people think may actually be protective. Small amounts of alcohol seem to reduce atherosclerosis — red wine in particular, but you could say the same thing about brightly colored fruits, vegetables and fruit juices. They are rich in anti-oxidants of various kinds that probably play a role in mitigating against lots of degenerative diseases.

There's been a lot of interest in whether the Mediterranean diet — in this case it's usually designed as fresh fruits and vegetables, olive oil, small amounts of cold water fish (Omega 3 fatty acids), a lack of saturated fats and red meats, lots of grains and red wine — may be a model for a preventive diet for Alzheimer's disease.

Is there a certain age where if you haven't got it, you're home free?

I wish that were the case, but probably not. If you look at the risk of Alzheimer's, it roughly doubles with every decade of life after 65. If you look at people at 65, probably only 1 or 2 percent have dementia. People at age 95, about 50 percent of them have dementia. The bulk of them are Alzheimer's disease.

So if you have your 90th birthday and you don't have any symptoms...

You could still get it. We don't have a perfect answer to that question, because there seems to be a small cadre of people whose bodies function exceptionally well, and they live to be extremely old, and they have clear thinking, they don't take medications, their function and ambulation are good. That subset of people is really fascinating, but that's a small group of people.

How important is your well-being: just to be happy, well-balanced?

As a psychiatrist, I think balance is important in everything. Quality of life is probably more important than quantity of life.

But there is an association between late-life depression and Alzheimer's disease. The nature of that association is not completely clear. In the not-too-distant past, we thought depression was a risk factor for Alzheimer's. Increasingly, it appears that depression is probably an early symptom of Alzheimer's disease.

In that silent period, when the brain is changing, if you know what to look for, there are some early signals, and late-life depression may be one of those. So a person may have some mood symptoms that pre-date the memory symptoms. You can't diagnose Alzheimer's, but we're beginning to suspect that's part of what's happening.

And then once people develop Alzheimer's, they clearly not only have changes in thinking, but they have changes in everything the brain controls. They have mood changes, personality changes, depression, apathy sometimes; agitation or psychosis can occur, especially later in the course of Alzheimer's disease. So psychiatric symptoms are common, and the bulk of the symptoms are either psychological or psychiatric, however you want to categorize them. And that's how psychiatrists sort of get into the act.

There's a whole field of psychology and psychopharmacology that has to do with managing behavior problems in Alzheimer's disease, which has gotten to be a very complicated and controversial area, because it has to do with the use of anti-psychotic drugs. Clearly those drugs can be helpful, but they come with a high potential consequence of side effects: sedation; problems with gate, balance and falling; sometimes swallowing problems. And the FDA has recently weighed in and issued a series of advisories that have suggested that there's an increased risk of stroke or overall mortality in demented elders who are given anti-psychotic drugs.

It's a real conundrum when you have someone who's assaultive or agitated, because we don't have a lot of good treatments. The other treatments we have to offer are far from perfect. I have patients who are on anti-psychotics, but we're trying to keep those drugs to a minimum.

Do suicide rates increase when people are diagnosed with Alzheimer's?

Suicide rates are high with people with late-life depression generally. It's not clear that with Alzheimer's disease per se, the rates are higher.

We actually did a study in Kentucky about 10 years ago, and the suicide rates for elders were about double the general population. In that group, about 90 percent of the suicides were men, and about 90 percent of those were white men, and about 90 percent of them shot themselves. So in other words, the profile of suicide in our society, you can say the people at highest risk are depressed, older white men who have access to a firearm.

Have we missed any issue we should be asking about?

It's worth talking a little about diagnosis. If you have a person in your family you're concerned about, or if you see this in yourself and your memory impairment is such that if effects your ability to do your normal activities, you really should get an evaluation. A lot of people we evaluate don't have Alzheimer's. Some have depression, anxiety, substance abuse or other problems that may impact memory.

There is a built-in denial with Alzheimer's that affects a person, so they don't always recognize it, and a lot of times the family sort of colludes with that. It's part of how families work. We don't want to see our relatives declining. We get worried about it and sometimes over-react, but sometimes we sort of blind ourselves to it all.

There's also the feeling that if you find out you have it or a family member has it, what can you do anyway.

We used to be very reluctant to diagnose Alzheimer's because (A) there was this conundrum of knowing the person had dementia, but not knowing for sure that they had Alzheimer's because we don't have an iron-clad diagnostic test, and (B) we weren't sure what we would do about it if we found they did. So we tended to delay or obfuscate the diagnosis, or maybe not share our suspicions.

Our field has gone in the other direction. Now we believe it's important to evaluate a person to be sure they don't have some other condition that could be treated or managed, either as a cause of memory impairment, or maybe layered on top of early Alzheimer's disease: a thyroid disorder, low B-12, what have you. We like to counsel people about diet, lifestyle and other factors that might be somewhat within their control.

Clearly that's going to be more impactful if you do that in the very early stages. We do have medication that while not curative might modify the symptoms and forestall the more serious symptoms of the disease for a period of time, and those are much more valuable early in the course of the disease than they are later.  And also, in terms of life planning, people deserve to know what their diagnosis is and what's wrong with them, even if the diagnosis is not absolutely clear. So if somebody sees me and it's apparent they have memory impairment, but I'm not sure whether it's truly Alzheimer's or what direction it's going to go, I think I need to share that with that person because they need to talk to their family about wills, estate planning, end-of-life care, powers of attorney, their preference for how their life should be managed, particularly so other people in the family know before they become incapacitated, because then it's too late. If you do that, you can spare a lot of anguish for the patient, and especially for the family later on.

As you look back on it, did you see symptoms in Ronald Reagan when he was president?

I did not, but there has been a lot of speculation that the press in the last few years of his life protected him, and that they did know that there was a problem. It was a more subtle problem than what happened to Woodrow Wilson, where the people close to him knew what was going on, but they weren't sure enough that they wanted to go public with it. That apparently was true with Reagan.

I think what happened to him — this is a good illustration: He was shot. He was much more seriously injured than we knew. He lost a lot of blood, and he probably had a significant cerebral vascular insult — if not stroke, he clearly had low blood volume, low blood pressure sustained for a period of time. And he was never really the same after that.

And after he finished his second term, he had a fall. He fell off a horse. He had a subdural hematoma. It was right after that his symptoms were just undeniable.

That's a good model for what happens to people with Alzheimer's. He probably had the plaques and tangles developing, but some other incident had to occur to accelerate the process. We know, for instance, that stroke accelerates the process of Alzheimer's disease, and he probably had something similar to it when he was injured, when he was shot.

Head injury clearly accelerates the risk of Alzheimer's, especially if you have a particular genotype. That has contributed to our concern about head injury in general. That's one reason why organized sports groups — the NFL is probably the best example — are looking at dementia, repetitive concussion syndrome. Even groups like soccer groups are a little bit worried about kids who head the ball — whether that might have some impact later in life. You can actually measure changes in cognition of kids who have headed soccer balls in practice. This, unlike football, is not a settled fact, but there have been reports in sports medicine journals. The soccer leagues are beginning to pay attention to that.

We haven't seen it to my knowledge in soccer, but we've definitely seen it in ex-NFL players. There are a lot of examples of ex-NFL players.

Some of them have had 20 concussions.

Apparently if you have a concussion, and you go back and play and have another concussion before the first one heals, your risk of some kind of untoward event is really magnified. The more often that plays out, the more significant the risk factor becomes.



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