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.”

 

Copyright 2007 The Psychology Lounge/ TPL Productions, All Rights Reserved

More Evidence That Psychiatrists Take “Payments” From Drug Companies

Two new articles from the New York Times confirm my earlier article about psychiatrists taking large amounts of money from drug companies, which tends to influence how they prescribe medicines. The first article documents how psychiatrists in Vermont received more money than any other medical profession. Each psychiatrist received an average of $45,692 in drug company bribes payments. Does this influence how psychiatrists prescribe? You bet! As the Times said, “For instance, the more psychiatrists have earned from drug makers, the more they have prescribed a new class of powerful medicines known as atypical antipsychotics to children, for whom the drugs are especially risky and mostly unapproved.”

Another article, also in the Times, documents that the federal government is starting to look at these practices. The Senate had hearing where they quizzed drug company execs about their practices. My favorite moment in the hearings came when Senator Claire McCaskill was talking about the Senate barring senators from accepting meals from lobbyists. And there should be full disclosure of any gifts or payments to senators. Then she said, “And if it’s good for Congress, it’s good for the medical profession in terms of cleaning up all this lobbying — because that’s what it is.”

You know doctors are in ethical trouble when the closest comparison is the Senate!

Once again, how should we deal with this? First, write to or call your legislators, both state and federal, and ask them to pass legislation to bar the practice of doctors taking money from drug companies. Any payments much be fully and publicly disclosed, and should be limited to a token amount like $100 per year.

Second, ask any psychiatrist you see if they receive money from drug companies and if yes, ask them how much and from what companies. If they refuse to disclose this, consider another psychiatrist. Once you know which companies they took money from, then you can evaluate whether it seems to influence their prescribing practices.

There are many psychiatrists who don’t take money from drug companies, and we should favor these doctors.

Copyright 2007 The Psychology Lounge/TPL  Productions

The Physiological Mechanism for How Stress Affects the Brain


For those readers curious about the mechanisms by which emotional stress affects brain function, I found an interesting piece of research about the physical mechanisms for how chronic stress can induce brain changes that could lead to cognitive impairment.

Scientists at Salk Institute for Biological Studies subjected mice to mild chronic stress for two weeks. What they found was fascinating. First some background on the physiology of Alzheimer’s disease. As the article explains:

“Alzheimer’s disease is defined by the accumulation of amyloid plaques and neurofibrillary tangles. While plaques accumulate outside of brain cells, tangles litter the inside of neurons. They consist of a modified form of the tau protein, which–in its unmodified form–helps to stabilize the intracellular network of microtubules. In Alzheimer’s disease, as well as various other neurodegenerative conditions, phosphate groups are attached to tau. As a result, tau looses its grip on the microtubules, and starts to collapse into insoluble protein fibers, which ultimately cause cell death.”

So basically, when phosphate attaches the the tau molecules, it causes them to change from helpful molecules to damaging the neurons.

The mice research found that the brain-damaging effects of negative emotions are relayed through the two known corticotropin-releasing factor receptors, CRFR1 and CRFR2, which are part of the body’s central stress mediation system.

So what does this all mean? It suggests that we have to protect our brains from stress, particularly chronic stress. Occasional stress doesn’t cause problems, but daily chronic stress does. The mice only showed permanent brain changes after 2 weeks of daily stress.

So stress management through cognitive behavioral therapy (CBT) or other means is not just a nice comfort option, but may be essential if you want your brain to last. Emotional pain doesn’t just cause emotional damage, it also damages the brain.

Perhaps scientists will be able to develop drugs that change CRF1 and CRF2 levels, but in the meantime, better take up that yoga, meditation, relaxation exercise, or CBT stress management program!

Copyright 2007 The Psychology Lounge/TPL Productions

Is Your Shrink Being Paid to Give You Drugs? The Secret Link Between Psychiatrists and the Drug Industry

Regular readers of this blog will remember my earlier article on Rebecca Riley, the young girl whose overtreatment with powerful psychiatric drugs may have led to her death.

Now it turns out that some psychiatrists may actually be getting paid by the drug industry to give kids powerful drugs! And this is in spite of an almost complete lack of evidence that these drugs work or are safe for children.

The New York Times has an article called Psychiatrists, Children, and Drug Industry’s Role, and this scary article documents the secretive practice of paying psychiatrists to prescribe certain drugs.

The article documents that more than half a million children are now receiving atypical antipsychotics such as Risperdal, Seroquel, Zyprexa, Abilify, and Geodon. These drugs have never been tested on or approved for use in children!

In Minnesota alone, the only state that requires such reporting, from 2000 to 2005 payments from pharmaceutical companies to psychiatrists soared by six times, to $1.6 million, and the rates of prescribing antipsychotics to children went up by nine times.

And the Times found that the money worked. Those psychiatrists who received more than $5000 from the drug companies wrote 3 times as many prescriptions for atypical antipsychotics than those doctors who got less or no money. Other interesting figures are that the average payment to psychiatrists was $1750, with a maximum of $689,000. (Nice work if you can get it!)

I should point out that atypical antipsychotics are not benign drugs. Side effects can include rapid weight gain that leads to diabetes, and movement disorders such as tics and dystonia, which can lead to a lifelong muscle disorder.

The Times describes one unfortunate girl, Anya Bailey, who was given Risperdal for an eating disorder by her psychiatrist George Realmuto, who had received more than $7000 from Johnson and Johnson, the maker of Risperdal.

Although the drug helped her gain weight, she also developed a painful and permanent dystonia in her neck that now causes her chronic pain and a movement disorder, even after stopping the drug.

And she was never given any counseling for her problems, only drugs!

So what can we learn from this article? First of all, the practice of paying psychiatrists to prescribe certain medications is widespread, but only Minnesota requires full disclosure. We should pressure our legislatures to mandate full disclosure in every state. Write to your state and federal congress and senate and ask them to either ban this practice or to require full disclosure, on the web, by name of doctors, of how much money is given by each drug company.

Secondly, when you take your child to a psychiatrist, you should ask them for a full written disclosure of any money they received in the last few years from drug companies for speaking, or for research. Payments to psychiatrists (and other M.D.’s) are disguised as speaking honorariums or research payments, but when a doctor receives $5000 for giving one or two talks, it is safe to say that they are being paid for something else. If the psychiatrist admits to receiving money, then you should probably find another psychiatrist, as this creates a bias to prescribe that I do not think can be overcome.

Third, you should be dubious about any suggestion to give your child an antipsychotic medication for any diagnosis other than true psychosis. This means that unless your child is actively hallucinating, and delusional, i.e. “crazy” there is no evidence that antipsychotics will help them. For instance, there was only one well-controlled study of the use of atypical antipsychotics in bipolar illness in children, and it found little or no difference between using the antipsychotic and not using it. And most of the children in the group receiving the antipsychotic dropped out of the study due to side effects. A second study by the same researchers found no advantage to using antipsychotics.

Fourth, consider taking your child to a psychologist or counselor rather than a psychiatrist. Psychologists don’t receive money to influence their treatment decisions and use behavioral approaches that don’t have side effects. And there is much more research evidence that supports the use of these behavioral approaches in childhood disorders. Dangerous medications should be reserved for second or third line treatments only. Remember the old saying that to a young boy with a hammer everything becomes a nail, similarly to a doctor whose specialty is giving drugs, all problems become biochemical.

Finally, let’s put pressure on our legislators to outlaw this thinly disguised bribery, which threatens the health of children and adults. Shame on the pharmaceutical industry! And even more shame on psychiatrists, who of all people should be trustworthy and not willing to accept such bribes. I make the perhaps radical suggestion that patients boycott psychiatrists who accept money from drug manufacturers. If doctors can’t earn a decent living without taking payments from drug companies that often have the appearance of bribes, then perhaps they need a new profession. I realize that there are decent, honest psychiatrists who either don’t take drug company money or don’t let it influence them, but I suggest that it may be hard to tell the difference unless psychiatrists employ full disclosure.

Copyright 2007 The Psychology Lounge/TPL Productions

The Mind-Body Connection: Depression and Its Effects On Physical Health

I will return to the theme of happiness in a few more days, but today we will continue with our series about depression, based on Peter Cramer’s book Against Depression, which I heartily recommend to anyone who wants to learn more about depression.

Depression is not just a psychological disease. It impacts the whole body, and especially impacts the cardiovascular system. Depression is one of the strongest predictors of cardiac disease. Even minor depression increase the risk of cardiac disease by 50 percent. Major depression increases risk by 3 to 4 times. For those with pre-existing coronary artery disease, risk is increased 5 times!

You might be thinking that this is no surprise. Perhaps depressed people smoke more, exercise less, eat more bacon, etc. What is surprising is that the numbers in the preceding paragraph are after adjusting for lifestyle and behavior! The raw numbers are even higher!

Why is this? What is the mechanism by which depression reeks havoc with the cardiovascular system?

There are several possible mechanisms. One is through the impact on blood clotting.

Blood clotting is controlled by cells in the blood called platelets. The stickier the platelets are, the more likely you are to develop blood clots, which can lead to stroke or heart attack. Depressed patients have stickier platelets.

Another mechanism is stress. Depressed patients are under constant physiological stress, with excess stress chemicals circulating in their blood. This may raise blood pressure and cause other changes that affect the cardiovascular system.

So what happens if you treat depression? Does this reduce risk of cardiovascular disease?

Studies of antidepressants given after heart attack show a 30 to 40 percent reduction in subsequent heart attacks and deaths.

Antidepressants improve the outcomes after stroke as well. When stroke patients were given either antidepressants or placebo, 66 percent of the antidepressant group survived 2 years, but only 35 percent of placebo group.

Other physical triggers like treatment with interferon for hepatic C and melanoma can also cause depression. In fact, 50 percent of patients who receive interferon will get seriously depressed. Depression in these cases is serious because it can cause the person to stop taking a potentially life-saving treatment.

Antidepressants help even in these cases of drug induced depression. One study found that treatment with Paxil, an antidepressant, reduced depression from 45 percent to 11 percent.

What are the implications of these finding?

  1. All patients who have had a heart attack or a stroke should probably take an antidepressant.
  2. All patients taking long-term interferon treatment should begin taking an antidepressant several weeks before starting the interferon.
  3. Probably most seriously ill cancer patients should take an antidepressant as well.
  4. Counseling that focuses on evaluating and treating depression should be part of any seriously ill medical patient’s treatment regimen.

Copyright 2007 The Psychology Lounge/TPL Productions

All Rights Reserved