Scientists Try to Discover the Earliest Signs of Alzheimer’s disease (Is Alzheimer’s a Lifetime Genetic Disease?)


Today’s New York Times has a fascinating article about current research in Alzheimer’s called Finding Alzheimer’s Before a Mind Fails. It is simultaneously encouraging and deeply disturbing.

The encouraging part is that researchers are discovering ways to examine patients that can find evidence of Alzheimer’s many years before the disease manifests itself in symptoms. A radioactive dye call Pittsburgh Compound B (PIB) is injected into the patient. This dye attaches itself to amyloid plaques in the brain, and then these can be seen by using a Positron Emission Tomography (PET) scan.  Studies using PIB have found the astonishing fact that amyloid plaques are found in 20-25 percent of people over 65 who appear normal! If the amyloid hypothesis is accurate, then many of these people will go on to develop Alzheimer’s disease.  Using PIB testing we could predict more accurately who will develop the disease, and perhaps develop prevention methods much like we give statins to heart patients who have plaques in their arteries. This is encouraging.

Someday in the future hopefully we will be tested for early signs of Alzheimer’s disease in our 40’s, and those who at risk given medications that will prevent it, just like we do for heart disease now. This would make aging much less scary.

Current Facts About Alzheimer’s disease

But the current facts about Alzheimer’s are less encouraging. It is the sixth more common cause of death by disease in the U.S. Five million people over 65 have Alzheimer’s disease. Estimates suggest that perhaps as many as 16 millions will have the disease by 2050, which is a staggering number that would bankrupt the health care system. (Of course, this assumes that in 43 years we have made no progress in the treatment and prevention of Alzheimer’s disease, which is absurd.)

Costs are already staggering–$148 billion dollars per year, and are increasing every year. Why? Here’s the dark truth. Alzheimer’s disease is a disease of the elderly. Almost 40 percent of those who live past 85 will eventually develop Alzheimer’s disease. The problem is that medical improvements are curing the diseases that used to kill us well before 85. One of the reasons Social Security starts at age 65 is that until recently, most people didn’t live much past the age of 65. Now as we defeat cancer and heart disease, and people stop killing themselves with diet and smoking, we are living into our 80’s and 90’s.  And getting Alzheimer’s disease.

What is Alzheimer’s disease?

Let’s talk a little more about what Alzheimer’s disease really is. Everyone worries about Alzheimer’s disease as they age. But some forgetfulness is completely normal. (We hope.) There is a old joke about Alzheimer’s disease which actually is a useful rule of thumb, it’s not a big deal if you forget where you put the car keys, as long as you can remember what keys are for. It is significant changes in memory and problem solving that are more worrisome.

When does Alzheimer’s disease begin?

This is a mystery currently. Conventional wisdom says that Alzheimer’s disease may begin a few years before symptoms appear, but some scientists question this. Because the brain has a lot of spare capacity, it may take years of deterioration before we lose enough brain function to notice. This may explain one of the common findings that the more highly educated (and probably more intelligent) develop Alzheimer’s disease as  a lower rate. They may have more spare capacity. If you start off with an IQ of 150, and lose a third of your brain functioning, you end up with an IQ of 100, and can still function. Start at IQ 100, lose 1/3, and you now are functionally retarded with an IQ of 66, and you won’t be able to live independently.

One scientist, Dr. Richard Mayeux, who is a professor at Columbia University, says, “I think there’s a very long phase where people aren’t themselves.”

If Dr. Mayeux asks family members when a patient’s memory problem began, they almost always say it started a year and a half before. If he then asks when was the last time they thought the patient’s memory was perfectly normal, many reply that the patient never really had a great memory.” (New York Times)

This is interesting and disturbing stuff. Other research finds that people who later develop Alzheimer’s disease showed lower intelligence scores even early in life, suggesting that perhaps Alzheimer’s disease is a genetic disorder that affects the brain in subtle way even early in life. If this is true, then the data on highly educated people may have been interpreted in a backwards way—instead of higher education preventing Alzheimer’s disease, it may be that Alzheimer’s disease prevents higher education!

 

Treatment of Alzheimer’s disease

Currently there are drugs that address the symptoms of Alzheimer’s disease, but no drugs that address or slow the underlying disease progress. The good news is that there are numerous studies attempting to find drugs that will actually address the underlying disease process in Alzheimer’s disease. The bad news is that no one really knows exactly what that underlying disease process is.

There are two finding from examining the brains of those with Alzheimer’s disease. The first is that they show plaques of beta amyloid between the nerve cells of the brain. The second is that the brains show tangles inside nerve cells made of a protein called tau. This damaged tau kills the nerve cells because they no longer get nutrients.  Both these are well-established facts, but no one knows what is the relationship between beta amyloid and tau, and how much each contributes to Alzheimer’s disease.

 

What Society Should Do About Alzheimer’s disease?

So what can we as a society do about Alzheimer’s disease? My grandfather used to say, “Everyone dies, so it’s just a matter of how you die.” By choosing to treat or prevent heart disease and cancer, are we choosing to die from Alzheimer’s disease?   This is a scary thought.  It’s clearly worse to outlive your mind than to outlive your body. And Alzheimer’s disease puts huge burdens on society and caretakers. Maybe we should start a campaign to encourage cigarette smoking in the elderly! (Or motorcycle riding, but this might make the roads a bit dicey.) 

More seriously, we are in the unfortunate window of time where we have successfully improved longevity without really addressing this core disease of longer life, Alzheimer’s disease.  Society desperately needs to find an Alzheimer’s disease cure or preventative treatment. Without this we will as a society incur great costs and individual suffering. I believe that this should become a top priority of private and government research spending. First we need better basic research to find out what the disease process of Alzheimer’s disease looks like. Then we can develop effective drugs to block or reverse that disease process.

In the meantime, all we can do is not worry too much, since stress may damage the brain. Eat healthy, exercise, maybe take some anti-oxidant vitamins, and hope that science can solve this puzzle so we can get old without losing our brain function.   

As for me, I aspire to these not-so famous words of the comedian Will Shriner, “I want to die in my sleep like my grandfather… Not screaming and yelling like the passengers in his car.”

 

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