Could you run through the basics of the disease, the different stages of it?
Alzheimer’s disease is a neuro-degenerating disease, so that means that brain cells die during the disease and they tend to die preferentially in areas that are important to memory early on in the disease, but eventually it involves the whole brain. There is a change in the biochemistry of the brain that happens in Alzheimer’s so that the two normally occurring proteins change slightly and then begin to accumulate in the brain.
When Alois Alzheimer first described Alzheimer’s disease, he really talked about the plaques and tangles, that is, the two different kinds of lesions that were really an accumulation of these slightly altered proteins. As these proteins accumulate, they cause the death of brain cells. As the brain cells die, they lose connection, obviously, with other brain cells and now we begin to have some pathways that aren’t working anymore.
The brain is a wonderfully redundant device, so we can lose pathways and still function fairly normally, but eventually we will lose enough pathways that we will begin to see changes in people’s behavior. They will begin to have memory problems and those memory problems get fairly extreme as the disease progresses and they will also show other kinds of difficulties, such as behavior difficulties that involve paranoia and delusions that are all related to the lack of connection between brain cells. That loss progresses until, eventually, death — Alzheimer’s disease is a fatal disease. There is enough brain tissue damage that people can’t do essential bodily functions, such as breathing and swallowing.
In your experience with the current research, is it primarily focused on the cause of these neurofibrillary tangles, this build up of plaque?
The current research is really aimed at trying to find the causes of Alzheimer’s disease, and to use the pathways and those causes of Alzheimer’s disease as potential therapies. So we know a lot about the biochemistry; about how plaques and tangles get formed. But in fact, we are still working on those medications that will interrupt that pathology, so there are a number of late-stage clinical trials that are going on now. These are the kinds of clinical trials that are the trials that happen just before drugs are licensed for sale, so that is good because it means that they have come a long way. And we would like to see those finished, but, of course, one of the caveats for all drug development is that there are more drug development schemes that fail than succeed, many more. So we have great hopes for these medications. The good news is the medications being tested tend to be working in different ways, and so if one of those fails, it doesn’t mean that all of them are going to fail.
Dementia and Alzheimer’s are viewed almost as the same disease. Can you explain the difference between the two?
Dementia is a set of symptoms. It’s what people exhibit, so it is the memory loss, problems with perceiving, to behavior problems, proceeding to difficulties with feeding themselves and keeping themselves clean and safe — those are all outward symptoms. Alzheimer’s disease is actually a pathological disease that’s defined by plaques and tangles and the neurodegeneration of the brain.
Is there a large genetic component to Alzheimer’s?
Well, Alzheimer’s disease is both genetic and environmental. It is perfectly clear that both play a part. If we look at identical twins, that are about as close genetically as we can find, and we follow those twins over many years, what we can see is that there often is as much as 30 years difference in the onset of Alzheimer’s disease in a set of twins. So that clearly means that there is some environmental factor that is making a difference.
We also know that if we look in the population, having one parent with Alzheimer’s disease means you are more likely to develop the disease. Having two parents means you are about twice as likely. So that suggests that there is a genetic component as well.
Let’s talk about early-onset Alzheimer’s and what that looks like.
Early-onset Alzheimer’s disease is by definition Alzheimer’s disease that starts before age 65. We actually are seeing more of that as we speak. I think that is not because there is more of it, but rather because it is being recognized more commonly. It tends to come to attention for very different reasons than late-onset Alzheimer’s disease and it often presents as a workplace problem because these people are young enough that they are still in the workplace and they begin to have job performance problems. Typically, it is not recognized as Alzheimer’s disease because 48-year-old people are not supposed to get Alzheimer’s disease, so they will often be misdiagnosed as depressed, burned out, etc. to explain their job difficulties. Many of those people don’t get diagnosed with Alzheimer’s disease until they have lost their job on a performance basis and then they don’t have health insurance anymore.
Why is the diagnosis so difficult?
Well, the main reason is that, at least for early-onset Alzheimer’s disease, the medical profession makes diagnosis on the basis of likelihood. You are not supposed to have Alzheimer’s disease at age 48. So we are going to try to find another explanation that is more likely before we go to Alzheimer’s disease. The fact that there is not a simple laboratory test for Alzheimer’s disease aggravates this.
When should people really be concerned?
Well, I think people should pay attention to dementia-like symptoms as soon as they notice them because there is a tremendous benefit to early diagnosis. And unfortunately, no one wants to admit that elders in the family are no longer performing the way they were and there is also the complicating problem that the last trivial memory difficulty that you have is absolutely indistinguishable from the first pathological memory difficulty that you have.
Does Alzheimer’s disease affect men and women differently?
It appears that Alzheimer’s disease is the same disease in males and females. But in fact, more females get the disease than males. But that is largely because females are much tougher then us frail males and they live longer.
How many people are at home with Alzheimer’s?
Approximately 70% of the people with Alzheimer’s disease are still living at home and one of the reasons for that is that the number of people with Alzheimer’s disease is increasing.
Currently, every 71 seconds someone is going to develop Alzheimer’s disease and by the middle of this century, one person every 33 seconds will develop the disease. So you can see from those numbers that not only is this a common disease now, but it is going to become even more common as we move through the time when the baby boom population from post-WWII is most likely to develop the disease.
What are the reasons for the increase?
Well, the reasons for the increasing number of people with Alzheimer’s disease are multi-factorial. One is simply that we are living longer than we ever had before. The history of modern medicine has been that as the population has aged, we see new diseases arising. When people’s life expectance was only to their mid-20s, you didn’t see much heart disease, you didn’t see much arthritis, you didn’t see much diabetes, you didn’t see much of the Type II diabetes. You didn’t see much of any of the chronic diseases and you didn’t see hardly any Alzheimer’s disease. But as the population has had its life span extended, you began to see more of these diseases, and Alzheimer’s disease is the latest example of that.
Do you see a difference internationally in the occurrence of having Alzheimer’s disease?
If you look across the world, Alzheimer’s disease is everywhere. So there isn’t anywhere where people are spared from having this disease.
What are the most common medications given right now for the treatment of Alzheimer’s disease and what are their functions; does it slow the disease down?
Well, there have been five medications approved for Alzheimer’s disease. One of those isn’t used anymore because it had some side effects that were undesirable. So there are three medications that work the same. They are called cholinesterase inhibitors. What they do is they block the destruction of one of our neurotransmitters.
In the brain, brain cells talk to each other by releasing chemicals, and those are called neurotransmitters. So if you block the destruction of one of those neurotransmitters it is going to last longer. So one of the early findings in Alzheimer’s disease was that acetylcholine which is a neurotransmitter, was decreased during Alzheimer’s and by slowing the destruction of acetylcholine you could get some symptomatic relief from Alzheimer’s disease. That is, people would think a bit better, might be a little better at activities of daily living. Unfortunately these drugs don’t change the course of Alzheimer’s disease very much. That is, people tend to deteriorate at the same rate. So after a year or so they are likely to go across their baseline, across where they started and continue to go down. So while these drugs are useful to many, they are not ultimately successful.
There is another entrance into the treatment of the disease and that is a drug called Memantine, or Namenda is the trade name, it works in a different neurotransmitter system but it has about the same characteristics. While it can be used with the other drugs, and that may have some benefit, it has the same transient effect. It gives you some improvement but the progression of the disease continues. The real key is going to be the next generation of medications that are aimed at interrupting the progression of the disease. So you can give people a very early diagnosis and hopefully keep them in that early status where they are functioning and are happier themselves and they don’t require the great amount of care that late stage Alzheimer’s does.
Is there something you think the new administration really needs to pay attention to?
The new administration clearly has a number of serious problems on their plate, but the fact is that if they don’t do something about Alzheimer’s disease, they are going to end up with a set of circumstances that will be completely out of control by the middle of this century. And in fact, it will be so severe that it will bankrupt our health care system. And so the way to avoid that is to invest more in research into the causes and treatments of Alzheimer’s disease.
In real dollars, funding for Alzheimer’s research over the last five years has been decreasing and that doesn’t make sense. It is going to cost the federal government immense amounts of money to take care of people with the disease. It already does. And if they don’t put more money into finding the causes and treatments, they simply are going to be faced with those late bills for care and they are not going to be able to afford them.
The one thing that we do know about the Alzheimer’s issue is that if it isn’t important to people right at this minute, it is going to be increasingly so, because by the middle of the century, there isn’t going to be anybody who isn’t affected by the disease, one way or the other; either they have the disease, or they are taking care of someone with the disease, or they can’t get health care because the system has imploded because of all the Alzheimer’s people in it.
What are the most common medications for the treatment of Alzheimer’s disease and does it slow the disease down?
Well, there have been five medications approved for Alzheimer’s disease. One of those isn’t used anymore because it had some side effects that were undesirable. So of the remaining four, there are three medications that work the same. They are called cholinesterase inhibitors. What they do is block the destruction of one of our neurotransmitters.
In the brain, brain cells talk to each other by releasing chemicals, and those are called neurotransmitters. So if you block the destruction of one of those neurotransmitters, it is going to last longer. One of the early findings in Alzheimer’s disease was that acetylcholine, which is a neurotransmitter, was decreased during Alzheimer’s and by slowing the destruction of acetylcholine, you could get some symptomatic relief from Alzheimer’s disease. That is, people would think a bit better, might be a little better at activities of daily living. Unfortunately, these drugs don’t change the course of Alzheimer’s disease very much. That is, people tend to deteriorate at the same rate.
The real key is going to be the next generation of medications that are aimed at interrupting the progression of the disease. So you can give people a very early diagnosis and hopefully keep them in that early status where they are functioning and are happier themselves and they don’t require the great amount of care that late-stage Alzheimer’s does.
- This is an edited transcript of an interview conducted February 2, 2009.