August 27, 2010
NIH Podcast Episode #0116
Balintfy: Welcome to the 116th episode of NIH Research Radio with news about the ongoing medical research at the National Institutes of Health – the nation's medical research agency. I'm your host Joe Balintfy. And coming up in this episode we focus on aging and Alzheimer’s disease: We’ll hear about findings that provide insights into how the brain clears blockages; we’ll have a report on a gene related to Alzheimer’s diseases; we’ll get a perspective on living longer in the 21st century, and hear an interview about the direction of Alzheimer’s disease research. But first, this news update.
Balintfy: Eleven research institutions in 11 states will receive more than $6 million in federal funding to support research on substance abuse and associated problems among U.S. military personnel, veterans, and their families. The National Institute on Drug Abuse is collaborating with the Department of Veterans Affairs, to award grants that will examine substance abuse related to deployment and combat related trauma. The National Institute on Alcohol Abuse and Alcoholism and the National Cancer Institute are also partnering in this endeavor. Studies funded by the partnership should yield important findings about returning military personnel.
Women who report feeling stressed early in their monthly cycle were more likely than those who were less stressed to report more severe symptoms before and during menstruation. This association raises the possibility that feeling stressed in the weeks before menstruation could worsen the symptoms typically associated with premenstrual syndrome and menstruation. According to a recent study, women who reported feeling stressed two weeks before the beginning of menstruation were two to four times more likely to report moderate to severe symptoms than women who did not feel stressed.
News updates are compiled from information at www.nih.gov/news. Coming up next clearing blockages out of blood vessels in the brain, plus lots about Alzheimer’s disease and aging, right after this.
(BREAK FOR PUBLIC SERVICE ANNOUNCEMENT)
In Mouse Study, Researchers Discover New Mechanism for Clearing Blockages from Smallest Blood Vessels
Balintfy: Researchers have identified in mice a previously unknown protective mechanism by which the smallest blood vessels remove blood clots and other blockages from the brain. Uninterrupted blood flow is critical for brain function, and the brain has developed various ways to maintain it. Blockages in the smallest blood vessels can be cleared by processes that disintegrate or wash them out. However, not all blockages are cleared completely. Dr. Suzana Petanceska at the National Institute on Aging explains that even tiny blockages in the smallest blood vessels — called microvessels—are bad.
Petanceska: Obstructed blood flow, even in the tiniest microvessel, has negative consequences on the connections between nerve cells, which is how they communicate and this is how the brain operates, and on the general health of individual nerve cells.
Balintfy: Persistent blockage can reduce or stop blood flow, limiting the supply of oxygen and nutrients to the surrounding tissue and nerve cells. This, in turn, can lead to impaired communications between nerve cells and ultimately cell death.
Petanceska: So the body has developed a number of mechanisms to actually eliminate spontaneously occurring blood clots in these vessels. One is by what is called hemodynamic forces; clots are being just pushed through or squeezed through.
Balintfy: Another way, she adds, is the anti-clotting activity that exists in the bloodstream. Dr. Petanceska says scientists were curious to further investigate the ways that microvessels eliminate blood clots and to also examine the consequences when blood clots are not removed.
Petanceska: So, this was a study conducted in mice, where they used some cutting-edge new technology that allowed them to visualize.
Balintfy: She explains that researchers were surprised to see the cells known as endothelial cells basically reach out and surround clots and push them out of the microvessels after two to seven days.
Petanceska: So this was fascinating; this was neither anticipated nor previously described.
Balintfy: The researchers also found that the ability to move the blockage out of the blood vessel diminished with age. Dr. Petanceska cautions these are early results and this discovery needs to be followed up by much more research; but she says it could have broad implications.
Petanceska: First, this may hold true in other organs, not just the brain, and it is important in terms of understanding microvascular resilience in a number of body organs. Second is that given that this process may be compromised and less efficient in the aged brain, this may be part of the mechanism by which age-related cognitive decline occurs in humans, and this may also play into what are the early pathogenic steps for neurodegenerative disorders such as Alzheimer's disease that has a huge cognitive component.
Balintfy: She says this also may play a role in processes that are required for recovery after stroke. The findings were described in a recent issue of Nature by researchers at Northwestern University Feinberg School of Medicine. For more on this study, visit www.nia.nih.gov.
Gene Linked to Alzheimer's Disease Plays Key Role in Cell Survival
Balintfy: In this next report, we learn how scientists have discovered that a gene linked to Alzheimer's disease may play a beneficial role in cell survival by enabling neurons to clear away toxic proteins. Neurons are one of two basic types of cells in the brain. A study funded by the National Institute on Aging shows the particular gene helps cells digest and recycle unwanted proteins. However, as Anahita Hamidi reports, mutations in the gene disrupt this process.
Hamidi: For more than a decade, researchers have known that two particular genes: presenilin 1 and 2 play an important role in the development of Early-onset Alzheimer’s disease. A new study, funded by the National Institute on Aging and published recently in the journal Cell by Dr. Ralph Nixon and colleagues, demonstrates a newfound role of presenilin proteins. Dr. Lorenzo Refolo, program director at National Institute on Aging in the division of Neuroscience and Dementias of Aging Branch, explains the findings.
Refolo: What's new here is that Dr. Nixon and his group found that the presenilin proteins one of it's normal roles is to somehow regulate this endosomal-lysosomal autophagy system by creating the right kind of environment within the system to start degrading proteins—both normal proteins and toxic proteins. Nobody had any clue that this was a function of presenilin.
Hamidi: This newly discovered function of presenilin works as a type of housekeeping mechanism—removing unwanted and potentially toxic proteins from the cell. Scientists refer to this process as macroautophagy.
Refolo: Sometimes, cells produce more proteins than are actually needed and these proteins need to be cleared from the cell because if they accumulate they can lead to some unwanted sort of side effects, if you would. This is an organelle system, which is responsible for removing those proteins.
Hamidi: What makes a protein toxic? Dr. Refolo explains that this is not entirely understood. However, one thing that is known is that structure plays an important role. Sometimes proteins take on a particular shape referred to as a beta-pleated sheat. This structure, says Dr. Refolo, increases the probability of proteins clumping together in the cell, leading the cellular toxicity which as been implicated in alzheimer's disease.
Refolo: Somehow, this structure, as these proteins accumulate in the cell, give signals to cells, in the case of alzheimer's disease, to neurons that things are not going well and that the neurons start a degenerative process. Often what happens is that these toxic proteins not only accumulate in the cell itsef, but get outside of the cell so they're found extra-cellularly and this is also very bad because then they can affect not only the cell that's producing them but the cells surrounding that cell and it’s almost like a domino effect and these proteins get out sort of get loose and do their bad, dirty work in the brain.
Hamidi: In other words, mutations in the presenilin gene are unfavorable because (1) it leads to an increase in the ABeta peptides and (2) the mutations disable the cell’s housekeeping machinery from working properly, thereby increasing the amount of toxic proteins in the brain.
Refolo: It's bound to have some therapeutic implications and will probably give more encouragement to the pharmaceutical companies to pursue this drug target. But I think there's some more basic science that needs to be worked out. Again, what’s the signaling mechanism? Are any of the signaling macromolecules are they also drug targets for therapeutics? So it has very broad therapeutic implications.
Hamidi: For more information regarding the study visit www.nia.nih.gov. This is Anahita Hamidi, National Institutes of Health, Bethesda, Maryland.
Long life in the 21st Century
Balintfy: Over the last 100 years, life expectancy of humans has nearly doubled. Social scientists are looking at the effects of aging on the individual and society as a whole. Elizabeth Goers attended a recent Matilda White Riley Lecture in the Behavioral and Social Sciences. She shares highlights from the lecture in this interview with the speaker, Dr. Laura Carstensen.
Goers: Dr. Laura Carstensen founded the Stanford Center on Longevity. For over 20 years, Carstensen has received funding from the National Institute on Aging for her research and recently spoke on the NIH main campus for the Matilda White Riley Lecture.
Carstensen: With this near doubling of life expectancy we now need to apply science and technology—medical science, social science — to solving the problems and challenges of people 50 and olderr. What we’ve really done so far in the history of science is to think about, attack, and solve problems of people 50 and younger. It’s really been all about solving acute diseases, improving infant health, reducing second heart attacks in middle aged people. We’ve really done a lot and come far there. We have a long way to go in the treatment of chronic diseases and conditions like Alzheimer’s disease that come on gradually and probably reflect some cumulative process that is taking place for decades.
Goers: Much of the focus of research looks at the problems of the aging mind such as poorer memory, degradation of reading comprehension, and more difficulties with multi-tasking and concentration. But Dr. Carstensen explains some of the advantages people gain as they age.
Carstensen: It turns out there are other aspects of cognitive and emotional function that actually improve with age and these are really very relatively recent discoveries that is people are better able to regulate how they feel, their feeling states, they are better at social relationships. Sometimes I think the slowing that comes with age may add to that. That is if you are talking about how quick does someone become enraged, well that probably slows down too. So there are some of those changes in emotional functioning that seem to improve, and changes in emotion also interface with changes in cognition, since much of what we do in day to day life involves both. So we do see some improvements. There are a number of people who are studying wisdom and it seems that wisdom, knowledge about life, being able to solve practical problems of everyday living improves, so a lot of what we think of as sort of being smart in life are involved processes that get better with age, not worse.
Goers: Due to the added years, Dr. Carstensen feel there needs to be changes as our population ages instead of just tacking all the additional years on to the end of our lives for leisure.
Carstensen: You know in my mind there could be nothing better than to double the length of time a species survives—for the species. What could be better than to have twice as long than your ancestors to live your life, to realize your goals, to be with the people you love and care about, to contribute, I mean this is terrific. There's nothing inherently wrong with longer lives, but there is something terribly wrong with adding years of life and not changing the way we live. So if we fail to change the way we live and continue to, say get all of our education by the time we are in our early 20s and then that's done, work like as hard as you can from your 20s to mid 60s and then now say you are going to have leisure for the first time ever by the way because you are working so hard earlier either studying or earning a living—then that’s not going to work.
Goers: For more information on aging, visit the NIA home page at www.nia.nih.gov. This is Elizabeth Goers, National Institutes of Health, Bethesda, Maryland.
Balintfy: For more on the Matilda White Riley Lecture series, visit the website obssr.od.nih.gov. Coming up next, more on Alzheimer’s disease.
(BREAK FOR PUBLIC SERVICE ANNOUNCEMENT)
Preventing Alzheimer’s Disease and Cognitive Decline
Balintfy: Alzheimer’s disease was first described in 1906 by German psychiatrist and neuropathologist Alois Alzheimer. He observed the pathological hallmarks of the disease in the brain of a female patient who had experienced memory loss, language problems, and unpredictable behavior. Since its first description, Alzheimer’s disease has gone from a rarely reported disorder to one of the most common disabling diseases among older adults.
To provide health care providers, patients, and the general public with a responsible assessment of currently available data on prevention of Alzheimer's disease and cognitive decline, the National Institutes of Health held a State-of-the-Science Conference called "Preventing Alzheimer’s Disease and Cognitive Decline." Dr. Neil Buckholtz was the planning committee chair, and is a topic expert: he’s chief of the Dementias of Aging Branch in the Neuroscience and Neuropsychology of Aging Program at the National Institute on Aging.
First Dr. Buckholtz, can you share some statistics on the prevalence of Alzheimer’s disease?
Buckholtz: Yes. It’s estimated that there are up to five million people in the United States currently with Alzheimer’s disease, and the projections are that by mid-century, there will be anywhere from 12 to 14 million people in the U.S. Worldwide, the estimates vary but probably about 20 million people currently with Alzheimer’s disease.
Balintfy: And part of the increase is because of the aging population?
Buckholtz: Yes. The major risk factor for Alzheimer’s disease is still aging, and the population, especially the group of people over 85, is the fastest growing group of people in the United States and actually around the world.
Balintfy: Dr. Buckholtz, what’s a good way to explain Alzheimer’s disease or cognitive decline?
Buckholtz: Basically, Alzheimer’s disease is an age-related irreversible brain disease that develops over many years. In the very early stages, the hallmark of Alzheimer’s disease is loss of memory. As the disease progresses, then other kinds of cognitive symptoms develop, such as language problems and decision-making problems. And then eventually, as the disease progresses to its very later stages, there are behavioral and personality changes that occur as well.
Balintfy: Which is tragic . . .
Buckholtz: Yes. Yes, it is very tragic both for the individual and for the families, because basically the person loses his or her personhood and the family — doesn’t remember the family members and the other people, the caretakers, and it’s very difficult to deal with for the family and the loved ones.
Balintfy: Are there treatments currently available?
Buckholtz: The current treatments provide some symptomatic benefit for a small period of time, maybe a couple years, but there are no treatments that are currently available that will delay the progression of the disease, although that is a major focus of the research that we do as well as pharmaceutical companies, trying to develop drugs that will slow the disease progression and eventually halt the disease progression. And the Holy Grail is prevention, in terms of preventing the disease entirely.
Balintfy: The NIH State-of-the-Science Conference was about prevention. Can you tell me a little about who was there and what they were doing, what they were discussing?
Buckholtz: The State-of-the-Science Conference was set up in collaboration with the National Institute on Aging and the Office of Medical Applications of Research at NIH to really determine the state of the science in prevention of Alzheimer’s disease and age-related cognitive decline. There are things put forward all the time which are purported to prevent Alzheimer’s disease, but the question was what is the actual scientific evidence for any of these things for preventing Alzheimer’s disease or age-related cognitive decline.
The people who were there were scientists who presented information and panel members who evaluated the information and made their final recommendation. The interesting aspect of this particular kind of consensus meeting that NIH puts on is that the panel members are not themselves scientists in the area of Alzheimer’s disease or cognitive decline; they’re basic scientists, clinicians, other kinds of people who are obviously very smart people, usually for other areas of disease, but are not themselves directly associated with Alzheimer’s disease.
Balintfy: What was learned? What were these experts able to share? And what was the end result?
Buckholtz: They evaluated various reports that looked at what is the literature, what are the studies that are available currently for trying to determine whether there are specific associations between anything — any drugs, any natural products, foods, physical activity, other kinds of things—that are suggestive of prevention of Alzheimer’s disease.
And again, it’s a very particular kind of analysis, because they look at a report that’s put out through the Agency for Health Research and Quality, AHRQ that evaluates these—basically the literature. And what they found was that there is no evidence that reaches what they call a high or medium level of evidence, but there are some things that are suggestive of associations. And the major recommendation was that more research needs to be done to firm up these kinds of associations.
So, for example, Alzheimer’s disease, there’s some suggestion that the risk of Alzheimer’s disease goes up with diabetes, with high cholesterol at mid-life, with depression, and may go down with omega-3 fatty acids—these are the constituents of fish, for example—fruits and vegetables, higher education, increased physical activity, but the data are not really pinned down sufficiently to make—actually make that recommendation. So, more research is needed to look at a variety of these different risk and protective factors to see what actually can be eventually recommended.
Balintfy: Would a simple way of explaining the conference be to say they were setting goals?
Buckholtz: Goals to evaluate—to do more research to look at these various factors to see if there are actually strong associations between these factors and prevention of Alzheimer’s disease and cognitive decline.
Balintfy: Do you feel that this conference will make an impact? Will these goals ultimately lead to better care for people?
Buckholtz: NIH is doing a number of these studies now to look at some of these factors, such as—in clinical trials, such as physical activity, and a number of epidemiological studies are looking at some of these other factors, such as fruits and vegetables, omega-3 fatty acids, fish consumption, those sorts of things. So, these are—some of these are ongoing; some of these things need to be done in a much more rigorous fashion, but I think these recommendations were quite good in suggesting how to go forward with the research agenda.
Balintfy: Thank you very much Dr. Buckholtz. For more information on the State-of-the-Science Conference "Preventing Alzheimer’s Disease and Cognitive Decline" visit the website consensus.nih.gov. For more information on Alzheimer’s disease and the latest research on it visit www.nia.nih.gov.
And that’s it for this episode of NIH Research Radio. Please join us again on Friday, September 10th when our next edition will be available. If you have any questions or comments about this program, or have story suggestions for a future episode, please let me know. Best to reach me by email—my address is firstname.lastname@example.org. I'm your host, Joe Balintfy. Thanks for listening.
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