November 23, 2008

Alzheimer’s Disease—i on NIH—episode #0016, segment 3

Scientists think that as many as 4.5 million Americans suffer from Alzheimer's disease. With November being Alzheimer's Disease Awareness Month, were featuring an interview with an expert on the subject. Dr. Laurie Ryan is with the National Institute on Aging. We start by asking what exactly is Alzheimer's disease?

Transcript

Welcome to “i on NIH”!

Featured in this month's episode are segments about featuring new information about prostate cancer screening, the opening of a new interactive exhibition, and an in-depth interview about Alzheimer's disease.

From the national institutes of health in Bethesda, Maryland — America's premiere medical research agency — this is “i on NIH”!

Covering health-research topics important to you and the nation, this public service vodcast is your information source from inside all 27 institutes and centers at NIH.

Half an hour, once a month, we'll show you the excitement of advances and the important information that comes from medical research.

And now, here's your host, Joe Balintfy.

Host: Welcome to the 16th edition of i on NIH! Coming up in this vodcast, we’ll have to experts explain new guidelines on prostate cancer screening, we’ll get a report on Global Health, and have an eye-to-eye interview about the latest research on Alzheimer’s disease. But first, have a news update. We turn to Harrison Wein at the NIH news-desk. Hi Harrison. What are the headlines you have for us this month?

Harrison: Great to be here, Joe. We've had some really interesting stories in our eColumn this month. I'll give you an update on egg allergies, warm people and where fat comes from.

Joe: Egg allergy is one of the leading food allergies in children. Doctors have usually told kids with egg allergy to avoid all foods that contain egg. Has that changed?

Harrison: Not yet, but a new study suggests that kids with egg allergy may be able to eat some baked foods containing heated egg. When they were tested in the lab, about 70% of kids with egg allergy were tolerant to muffins and waffles made with eggs.

Joe: But this was done under medical supervision.

Harrison: Absolutely. Don't try this at home. Some children can have serious allergic reactions to heated eggs.

Joe: But that's not all this study showed.

Harrison: The researchers told the kids who were tolerant to heated eggs in the lab to try adding baked egg products to their diets at home. In allergy tests, the kids eating baked eggs had weaker immune reactions to egg white proteins over 12 months. Now, this result suggests that the children eating heated eggs may be developing tolerance to regular eggs.

Joe: So that hints at a strategy to help alleviate some children's allergy to regular egg.

Harrison: Yes, but further studies will be needed to confirm that.

Joe: Now, you had an interesting story about the use of terms like "warm" and "cold" to describe people.

Harrison: New research shows this may not just be a linguistic oddity; heat sensations and psychological concepts are actually linked in our minds.

Joe: How did they do this study?

Harrison: The researchers recruited 41 college students. Each student was met in the lobby by a woman carrying a cup of coffee. During the elevator ride up, she asked the participants to hold her cup for a second while she wrote something down. Half the participants were given a cup of hot coffee and half iced coffee. Upstairs, they filled out a questionnaire about a fictitious person that was described to them. The described person was perceived to be significantly warmer by participants who had held the hot coffee cup than by those who'd held the iced coffee.

Joe: What about other character traits?

Harrison: The coffee temperature didn't affect the ratings on any traits that weren't related to warm/cold ideas.

Joe: And they found that temperature could also affect behavior.

Harrison: In another set of experiments, they found that people primed with physical coldness were more likely to choose a gift for themselves. Those primed with physical warmth, in contrast, were more likely to choose the gift for a friend.

Joe: This seems like it could have practical implications.

Harrison: Absolutely. Give people a warm handshake before an important meeting, and make a hot cup of tea before you ask your spouse about that new TV you've been eyeing.

Joe: The last topic you mentioned was where fat comes from.

Harrison: Yes, we know a lot about what fat cells do in the body-and it's more than just passively storing our extra energy. But researchers actually didn't know where the cells originally came from. It turns out that they come from the walls of blood vessels in fat tissue.

Joe: What's the significance of this finding?

Harrison: The interplay between the network of blood vessels in fat tissue and fat cells could provide potential targets for therapies to treat obesity. And that could have implications for obesity-related diseases, such as diabetes, heart disease and some cancers.

Joe: And where can people find out more about these studies?

Harrison: You can read about these and many other research studies in "NIH Research Matters." Go to the NIH home page and look for the link on the right-hand side, under "In the News" that says, "eColumn: NIH Research Matters"

Joe: And what's in this month's health newsletter?

Harrison: In the November "NIH News in Health" you can read about attention deficit hyperactivity disorder and the possible health risks of a chemical called bisphenol A, or BPA, which is found in many types of hard plastics. And be sure to check out our upcoming December issue with healthy holiday gift ideas.

Joe: And where can people find that?

Harrison: It's at news-in-health-dot-nih-gov.

Host: Thanks Harrison. Now for our first report. Not long ago, there was some updated advice regarding screening for prostate cancer. I on NIH turned to two experts, Dr. Barry Kramer from the Office of Disease Prevention and NIH, and Dr. Howard Parnes at the National Cancer Institute. Here’s what they had to say about prostate cancer screening.

Dr. Parnes: Prostate cancer is a very important disease. It’s the leading cause of cancer in men other than skin cancer. And it is the second leading cause of cancer death in men in the United States.

Dr. Kramer: The commonly available screening tests, the blood PSA, prostate specific antigen, and the digital rectal exam can pick up many cancers that we're not aware of, asymptomatic cancers that haven't caused any problems, and at least early analyses suggest that a substantial proportion of the diagnosis that are made by screening using either or both of the tests will pick up cancers that were not destined to cause the man any harm.

Dr. Parnes: Right, well, this is a very controversial area in terms of when should we consider PSA screening. Should it be offered to all men of a certain age? Is there a time, an age at which we should back off from prostate cancer screening? And there are numerous opinions, points of view, on this issue. Different medical associations from the American Cancer Society to the American Urological Association to the U.S. Preventive Services Task Force, and about a dozen others, have come up with guidelines for prostate cancer screening.

Dr. Kramer: The USPSTF, which stands for the United States Preventative Services Task Force, is an independent panel primarily of practicing primary care physicians.

Dr. Kramer: they look at different kinds of evidence, a wide array of evidence.

Dr. Kramer: and they concluded that that evidence was of low quality and specifically insufficient quality to judge the balance of the benefits and harms in men under the age of 75, but came to a stronger conclusion for men 75 and above. They concluded that the use of PSA and digital rectal examination to screen for prostate cancers should be discouraged, because they felt there was moderate to strong evidence that there would be a net harm if there were routine screenings of such men.

Dr. Parnes: Many people will say, well, “What’s the harm in knowing? It’s just more information.” But in fact there are a number of inherent harms for any screening test.

Dr. Kramer: Of course a very common side effect of screening tests in general is the anxiety that arises from a positive test. And in the case of prostate cancer screening, most positive tests are false positives, that is, the man turns out not to have prostate cancer. And so there is the common issue of anxiety, and that's been shown to be long lasting. There is a long lasting awareness of cancer, and a fear that the man may still have prostate cancer, even if they've been told they didn't, or if a prostate biopsy was negative.

Dr. Parnes: And in fact men with negative biopsies are the groups most likely to come back for subsequent biopsies. And in some men this can lead to biopsy after biopsy after biopsy every year, every few years. And they’re living with this hanging over their head. And it really can create a lot of stress. And these are men who do not have cancer.

Dr. Kramer: The needle biopsy can cause inflammation of the prostate or it can cause infection, and in a low percentage, generally five percent or fewer men will have a serious enough infections that antibiotics are required or they may even need hospitalization to take care of the infection. Now, those are the side effects of the screening and the direct down stream effects of the screening. In addition, if prostate cancer is diagnosed, then there are a number of even potentially more serious harms, and remember, at least some of the diagnoses are in men who's prostate cancer wouldn't have caused their death, and therefore, they don't stand to benefit, those particular men, from the treatment. They do stand to be harmed. The harms can be very serious.

Dr. Parnes: The big challenge and the shortcoming as I see it right now is that we’re really not very good at being able to identify who really needs to be treated and who can benefit from treatment, which are actually two slightly different things. Now, when people have very high-grade cancer, which is looking at the cancer cells under the microscope and giving a grade or a score, it’s true that that’s a group that we know needs to be treated. What we don’t know is if they’ll benefit from treatment, or more specifically which of those men will benefit from treatment.

Dr. Kramer: In a small percentage of men, perhaps half of a percentage, they can actually die of the treatment itself, particularly if it is a radical surgical procedure known as radical prostatectomy. Much more common from the treatment is the side effects on the urinary tract and on the colon and on sexual performance.

Dr. Parnes: But a very important result was published in 2005 in The New England Journal of Medicine, showing that surgery did save lives.

Dr. Kramer: I think that any time the intuitions are so strong that it seems counter intuitive, that the tests might have harm, is useful to emphasize, as USPSTF has, that there is more uncertainty than is common knowledge out there.

Dr. Parnes: Well, as you can tell from the discussion to this point, you know, it’s an involved sort of complex area. We don’t have complete information, which is often the case in medicine. And so we have to make the best decision really on a case-by-case basis, I feel, based on incomplete information.

Dr. Kramer: This is the first time that the USPSTF decided to divide its recommendations by the age of men. As I mentioned, men under the age of 75, they said there was insufficient information. That's because the benefits haven't been proven. There is no high quality evidence or even good quality evidence to judge whether or not there is benefit associated with screening those men for prostate cancer, but there are clear harms. And so for those men, they concluded that the benefits are theoretical, and the harms are real, and in some cases, unavoidable.

Dr. Parnes: However for the first time they are now saying that men 75 and older should not be routinely screened. Well, it’s a very interesting change. And one could argue that it’s perhaps not that much of a change. I think these new guidelines are very much in sync with what the AUA, the American Urological Association, has as their guidelines, and the American Cancer Society, which suggest that prostate cancer screening should only be offered to men with at least a 10-year life expectancy. Because the average life expectancy of a 75 year old is about 10-years.

Dr. Kramer: In a man who's 75 and above, it is much more likely that the man would go on to die of causes unrelated to prostate cancer, and couldn't even conceivably benefit from routine screening. The harms would be the same, if not more. The risks of dying of surgery are actually greater in men 75 and above, even healthy men, and those men have underlying heart disease, coronary, artery disease, and so it's likely that they wouldn't tolerate the therapy as well, and could go on to die of other natural causes before the benefits of screening could exhibit themselves.

Dr. Parnes: So I think it’s another way of saying the same thing, that we shouldn’t do mass population screening on 75 year olds because they don’t have a greater than 10-year life expectancy as a group. And so I sort of look at this as being consistent with previous recommendations. I do think it’s helpful to put it in these new terms, because we’re not very comfortable at estimating life expectancy. And this gives the health care provider reason to pause for a moment when talking to an individual in that older age group and say that you know, there is a task force that is recommending great caution. I mean, that’s maybe how I would rephrase what the task force recommendations are.

Dr. Kramer: We're working against very strong intuition that picking up cancers early must benefit people, but that's simply not true, because any test is going to carry some harms with it, and any treatment is going to carry harms with it. And just like any medical procedure, you need to balance what is known about the benefits against what is known about the harms. And in this case, we have more information and more solid information about harms than we do about benefits. And so it boils down to informed consent.

Dr. Parnes: And I think it’s a big challenge for primary care physicians, urologists, any health care provider who’s in the position of getting PSA tests. To do a proper informed consent is not an easy thing to do. And I think it often gets put aside. Physicians will say, “Well, let’s get a PSA test to rule out prostate cancer.” I don’t think that represents an adequate informed consent.

Dr. Kramer: The unfortunate fact of the matter is that for at least one of the screening tests, the PSA blood test, a man could be screened without his knowledge at all. In some cases, a PSA is included in a routine panel of blood work, so the man may think he is only being tested for a blood cholesterol or only being tested for blood sugar, when a point of fact, he's being screened for prostate cancer without his knowledge. So the first time he becomes aware that he's been screened for prostate cancer is when he gets a call that he has an abnormal blood test that could even suggest he has prostate cancer. Then it becomes very difficult to make a decision, because the man is no longer considering himself quite as healthy. He's worried that suddenly he faces a concern, an uncertainty that he actually has prostate cancer. And so the USPSTF concluded that it's much better for a man to go through the discussion before he is told that he is in a very high-risk group.

Dr. Parnes: As a general rule, I find myself in agreement with the U.S. PSTF guidelines, which is to say that we don’t have sufficient information to recommend for or against -- this is not an argument against doing it, it’s just that we have to recognize when the balance of information doesn’t clearly point one way or the other. And I agree with that in younger men. And I would tend to agree that in older men you really should think carefully, is this man likely to live long enough to benefit from screening, if indeed there is a benefit.

Dr. Kramer: There are biases that can make a test that has no benefit appear to be beneficial. The same biases can actually make a test that has a net harm appear to be beneficial. One of the most important biases is called lead time bias, that is a screening test will always pick up a cancer before it would have been picked up by the onset of symptoms from the cancer. And since we always measure the survival time of a cancer from the date of diagnosis, then even if you die on the very same day of the very same cancer, a screening test will make it appear as though survival is better, even when life expectancy hasn't changed at all.

Dr. Parnes: I think from a big picture point of view, and I don’t mean to sound pessimistic, but I think what it really comes down to is a balance of known risks versus potential benefits. To me the risks are more clear than the benefits. And the risks occur immediately, the benefits may occur later.

Host: Thanks to Dr. Howard Parnes at the National Cancer Institute and Dr. Barry Kramer from the Office of Disease Prevention and NIH. For more information on prostate cancer, visit www.cancer.gov. Also, for more from these experts, look for more excerpts from these interviews on YouTube. Visit the NIH4Health channel at www.youtube.com.

Host: The National Library of Medicine, the world's largest medical library and a component of the NIH, has opened a new interactive exhibition, "Against the Odds: Making a Difference in Global Health." The exhibition presents a look at the public health problems posed by Hurricane Katrina. Wally Akinso files this report.

Wally: The National Library of Medicine held an opening program for the new interactive exhibition, called “Against the Odds: Making a Difference in Global Health”. The audience consisted of high schools students from Washington D.C., Maryland and Virginia. Manon Parry, the curator of the exhibit, describes the purpose of the exhibit.

Parry: Against the Odds is a new exhibition at the National Library of Medicine that attempts to expand our understanding of global health to make us think about our role in our world community that shares values about what we can do to get involved in health, and the issues that we all care about, and also what are the things that affect illness? It’s a way to explore not just how diseases are spread by viruses or the role of bacteria, but to look at some of the basic things that interfere with quality of life. So that would include nutritious food, access to affordable health care, clean water and protection from violence.

Wally: CNN Medical correspondent Elizabeth Cohen was the moderator of the program. She evaluates the performance of the panelists.

Cohen: They were great. I thought that they really told the kids what they needed to know, which is they can become a part of an exhibit like this someday. They can really do incredible public health work, and they can do it starting now. The examples that were set -- Jeanie White and all of the other people who really showed what you can do.

Wally: The program featured individuals whose stories appear in the exhibition such as Dr. Victoria Cargill, director of clinical studies and director of minority research of the NIH Office of AIDS Research, Dr. Roger Glass, Director of Fogarty International Center and Dr. Jack Geiger, a founding member and past president of Physicians for Human rights. Dr. Donald Lindberg, Director of NLM also spoke to the large audience. He gives a play-by-play of the program.

Lindberg: Well, we’re outside the opening of our exhibition on global health. The audience has just come out from an auditorium. They have heard a really interesting set of presentations by students who are doing something in the world to make a difference and some older people who spent 40 or 50 years making a difference in health care delivery.

Wally: After the program the kids got the opportunity to check out the exhibit. Dr. Lindberg is optimistic about what young people can gain from the exhibit.

Lindberg: Well, I think the top expectation is that young people coming to see this will find something of interest and inspiration. Really, in that sequence, because I’ve stressed to them – or at least I’ve tried to say – we hope that you’ll find an inspiration to pick an area and make a difference socially in your own community or in your own group, whatever you’re interested in, but you can’t do that just by wanting to help. It’s nice to want to help. Medical profession, medical library people, they all want to help. But you have to know something. For the students it’s a priceless four years of high school and then college where they can learn anything. So it’s up to them to pick an area and to get a background in science or politics even, chemistry, motivational behavioral science, whatever that they can apply to accomplish something in society. That’s what we’re after.

Wally: Throughout the exhibit, harnessing the best of 21st century technology, engaging text and graphics, and interesting objects, “Against the Odds” focuses on how individuals and communities, in collaboration with scientists, advocates, governments and international organizations, have made and are making a difference in the health of people around the world. Various students shared their thoughts about what they experienced at the event.

Student 1: I thought it was really informative. I like seeing everything on the different countries and what was happening and the things we could do to fix it.

Student 2: I was inspired by the story of the two twin brothers and how they heard gunshots, and they were only 11 when they started an organization. So I wish I could do something like that too.

Student 3: It was very empowering because, you know, we live in high school. We hear all kinds of stuff every day. We think we’re little kids. We cannot do anything to change the world, but especially Ryan White, he helped me realize that we can do stuff to prevent all the things going on around here. It’s not about your age or your class. Anybody can help the world.

Wally: Ryan White was diagnosed with AIDS at the age of 13 and gained international notoriety fighting for his right to attend school. Jeanne White Ginder, mother of the late Ryan White and an AIDS activist, talks about her son’s battle with AIDS.

Ginder: Well, a few weeks after Ryan death, Senator Kennedy called me. I was feeling sorry for myself. I was just questioning God, questioning everything, why. Why did this happen to our family? Senator Kennedy called and said, “We would like for you to come to D.C.” I said, “No.” I said, “You know, Ryan used to do that, not me.” He said, “No, we really need your voice. I mean would like for you to come to D.C. and talk to senators.” Finally, Senator Hatch called me, and he said, “Jeanie, we’re not going to take no for an answer.” He said, “I have 20 senators lined up for you.” He said, “All they want you to do is tell these senators what it was like to watch your son live and die from AIDS.”

Ginder: This is one mom that has seen this epidemic through they eyes of moms and dads and seeing the suffering not only the person with AIDS but also through the eyes of the moms and dads in the families. So please, if something touches your heart, you go for it. Don’t think that you can’t do it because you can make a difference in the lives of people that you love and people that you care about. Thank you.

Wally: Against the Odds presents a look at the public problems posed by disasters such as Hurricane Katrina. It also profiles a campaign for oral rehydration in Bangladesh that was so successful that it has been adopted in Afghanistan as well. Parry says the exhibition highlights some of the achievements of people around the world who share a commitment to a better life and a healthier future for all.

Parry: We have photographs and artifacts from Act Up: The AIDS Coalition to Unleash Power. They actually stormed the NIH in the late 1980’s and early 1990’s to complain about the practices, medical research and the slow pace of development of new treatments for people living with HIV. So it’s an opportunity for us to look back on a community of people who, again, were not involved in careers in medicine but wanted to stand up and make a change in what was going on and how people with HIV were being treated.

Parry: We have the Nobel Peace Prize that was awarded to international physicians for the prevention of nuclear war for their work campaigning against nuclear weapons testing and towards a ban and a treaty to stop nuclear proliferation. We also have hundreds of photographs from stories all around the world of people making a difference in their own communities.

Wally: Parry says the exhibit provides NLM an opportunity to showcase some of the contributions that they are involved in.

Parry: It’s also a chance to highlight all the activities that other people outside have been engaged in collaborating around the world. It’s a way to look at how people can make a difference. So although people might feel overwhelmed by the scope of global health problems, it’s an opportunity to highlight some of the successes and look at some of the reasons behind why some of those problems last still to this day even though we’ve tried to make a difference, and think about strategies for taking those remaining challenging on and what we can do about them.

Parry: Some of the messages in the exhibition are about things that are universal issues that everyone can get involved in and all of us can care about. That includes a safe place to live, clean water, access to affordable health care and protection from violence. I think it’s an opportunity for us to invite a whole community, a diverse community of people to take on those issues and get involved in the fight for global health.

Wally: Parry says this exhibition represents the accomplishments of many individuals as well as the challenges that remain and also encourages others to join the fight for health and human rights. For I on NIH, This Wally Akinso.

Host: Thank you Wally. Scientists think that as many as 4.5 million Americans suffer from Alzheimer’s disease. With November being Alzheimer’s Disease Awareness Month, we’re featuring an interview with an expert on the subject. Dr. Laurie Ryan is with the National Institute on Aging. We start by asking what exactly is Alzheimer’s disease?

Ryan: Alzheimer's disease is a type of dementia, and actually it's the most common form of dementia in those who are over the age of 65. And dementia, simply, is a term that means you have a loss of cognitive function, of memory and thinking skills. It deteriorates over time.

Joe: Are the number of cases of Alzheimer’s disease increasing?

Ryan: Yes, unfortunately, because the population is getting older, and age is the biggest risk factor for Alzheimer's, we are seeing more people, and that trend is only going to continue unless we find a treatment that either stops or slows the progression of the disease.

Joe: What kind of treatments are available for Alzheimer’s disease?

Ryan: Currently, what we have available for patients are drugs that work on the symptoms. They're called acetylcholine esterase inhibitors -- Aricept, people might have heard of, Exelon — and those drugs treat symptoms. They don't stop the underlying disease pathology, though. And so, what's exciting now, is it’s in early-stage human trials, Phase I and Phase II, where drugs are actually trying to target the underlying disease to, like, stop or slow the progression of the illness.

Joe: Is there any researcher shedding more light on Alzheimer’s disease?

Ryan: Oh, absolutely, the interesting thing now is, like I said, we're finding out more about the disease mechanism, so, the basic science has really helped us to identify a couple of areas that we want to target. One is the beta amyloid protein, which has an abnormal build-up in the brain, and the other one is the tau protein, and now, there are new, Phase II, like I said, early phase clinical trials actually targeting both of these mechanisms.

Joe: What are some new treatments for Alzheimer’s disease that are being studied now?

Ryan: One of them is actually a nutritional supplement, Suvenade, that actually combines omega-three fatty acids, anti-oxidants, and a lots of other nutrients, to see if it can actually slow the progression of Alzheimer's, and they gave this to mild Alzheimer's patients, and, in fact, found that in the early, again, in the early phase trial, Phase II, found that there was a lessening of the cognitive decline. It didn't stop it, but it did slow it down, compared to the people who were on the placebo, the standard of care.

Joe: What are some other interesting areas of Alzheimer’s disease research?

Ryan: We are making great strides, now, with imaging, and also biological markers, in human blood and in the cerebral spinal fluid, of the underlying Alzheimer's pathology, and they're finding that we can actually look early on. You know, people, at least with his mild cognitive impairment stage, and, hopefully, move it even further back, to identify people who are at risk, and also these biomarkers, as we call them, will also be helpful for treatment trials. We would be able to see if there were changes, something like you might see in cholesterol on somebody with heart disease, and so that you wouldn't have to wait, you know, years to see if you’re slowing down the progression of the cognitive changes, which are not quick. They’re actually fairly slow over time, so, if we had a marker in blood or in spinal fluid, or even imaging, or a combination, we would be able to see if drugs were working faster, and, hopefully, find out sooner whether or not they were working, and also find out who might be the people to respond to the drugs.

Joe: For more about Alzheimer’s disease, visit www.nia.nih.gov/alzheimers. You can also call the Alzheimer's Disease Education and Referral Center at 1-800-438-4380. Be sure to ask for or look up the new publication: “Alzheimer's Disease: Unraveling the Mystery.” For more from Dr. Laurie Ryan at the National Institute on Aging, check out the NIH Research Radio podcast episode number 70 from October 31.

Host: And that’s it for another episode on i on NIH. Thanks for tuning in and please watch again next time. We’ll be back again next month with another episode. For i on NIH, I’m Joe Balintfy.