The controversy boils down to semantics, says Martha L. Daviglus, chair of the consensus panel and a preventive cardiology researcher at Northwestern University’s School of Medicine. “Obviously, smoking and hypertension are risk factors for cardiovascular disease,” she says. “And they may turn out to be risk factors for Alzheimer’s disease as well,” she says. But after reviewing all the evidence, Daviglus and her fellow panelists concluded that it “failed to provide convincing evidence” of the link, whereas other researchers see “some evidence” of a link.
Getting better data may be a problem, however. One of the best ways scientists have to prove cause and effect in medicine is to conduct a randomized controlled trial, in which study subjects are randomly assigned to two groups. One group—the so-called control group—receives the usual standard of care. The other group—the so-called experimental group—gets whichever intervention is being tested. The simplest way to prove that treating high blood pressure helps to delay the onset of dementia would be to treat one group for hypertension and leave the other group deliberately untreated for the sake of the experiment. No ethical physician would participate in such a study.
One way out of this dilemma, Daviglus notes, is to design a study in which patients suffering from hypertension get treatment, and doctors analyze the results based on how well the patients’ blood pressure was controlled. If the amount by which blood pressure dropped closely paralleled the decrease in dementia risk, that would be powerful evidence of a beneficial link. Such a so-called dose-response study has not been done yet—it is a complex and expensive undertaking—but there is reason to believe it could be worth the investment.
Observational studies, which follow people as they get older without directly intervening in their treatment, have uncovered some suggestive trends. Larson and others have shown that people who have good control of their blood pressure from age 65 to 80 are less likely to develop dementia. After age 85, controlling blood pressure does not have much effect on dementia risk. That doesn’t mean anyone older than 85 should stop taking blood pressure medication. Lowering high blood pressure still prevents congestive heart failure and promotes kidney health. But these studies suggest that doctors do not have to take aggressive measures when treating patients older than 85 for hypertension.
As for physical activity, the best evidence in favor of its benefits for the brain comes from Australia. Two years ago researchers there published the results of a randomized controlled trial of physical activity in 170 older adults who had started showing greater memory problems than their peers and were thus at increased risk of developing dementia. Study participants averaged an extra 20 minutes a day of physical activity over six months. The study was so rigorously designed that individuals undertook the extra exercise by themselves at home to preclude the possibility that the true benefit had come from socializing with other people during group activities. The benefits of extra exercise were obvious and lasted—albeit at a diminishing level—for 12 months after the exercise program ended. Not only did the experimental group score better on tests of their cognition compared with the control group, but the improvement was twice as great as the one that had previously been shown for the antidementia drug donepezil (brand name Aricept). This was the first time that anyone had proved in a randomized controlled trial that exercise could improve mental functioning in people with some cognitive problems.
No one understands on a biochemical level why physical activity might help the brain. The best explanation so far, says Henrietta van Praag, a neurobiologist at the National Institute on Aging, is that exercising the heart somehow stimulates growth factors to produce new nerve cells in the brain. In 1999 van Praag showed that more new nerves formed in the hippocampus—one of the key centers in the brain for memory and learning—in physically active mice than in inactive ones. (She was working at the time as a postdoctoral researcher in Fred Gage’s laboratory at the Salk Institute.) She has since shown that the new cell growth is associated with a marked improvement in learning and memory. The new nerves also show qualitative differences from their older counterparts. The younger cells are better at establishing new connections with other cells. The effect is somewhat temporary. After a couple of months, the new cells start acting like the older cells, although they do not die off.
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Add CommentThis is the third in our new section on the Science of Health. I'm curious what other topics you think we should cover.
Reply | Report Abuse | Link to thisAlthough I've written two of the columns, I will mostly be editing the columns from now on. The are reported columns that are based on evidence and are not opinion pieces. Ideally, they should examine the science behind an emerging consensus in a field, in an instructive controversy or an engaging mystery.
Let me know what you think, using the comments box.
A recent study published in the online peer-review journal, PLoS One, showed that daily supplementation of high doses of vitamin B (Folate, B12, and B6) over 2 years decreased the rate of brain atrophy in elderly individuals with mild cognitive impairment (MCI). MCI is a possible precursor to Alzheimer's.
Reply | Report Abuse | Link to thisThe B vitamins lowered plasma homocysteine levels. High levels of homocysteine have been shown to be associated with increased rate of brain atrophy, in addition to cardiovascular disease.
The study made no mention of physical activity level among the subjects in either group (control and active treatment). A study that could possibly combine the variables of the Australian study mentioned in this article with the variables of homocysteine-lowering B vitamins would be interesting to see.
I have cardiomyopathy and have suffered a couple of rounds of acute congestive heart failure. From my personal experiences, I think that it's curious that no mention was made in this article of the heart's critical role in extracting increasingly toxic waste products from tissues. Certainly the supply of oxygen and nutrients is crucial to cellular performance, but I have this suspicion that my thinking becomes less clear as cellular waste products accumulate in the brain. Rest seems to allow the extraction process to clear the accumulated wastes and clear my thoughts as well.
Reply | Report Abuse | Link to thisI suggest that the long term effects of increased tissue residency of cellular wastes be carefully investigated if they are not already.
The B vitamin story was immense as it showed that nutrition is a select population could benefit. But a fine point was left out, the study showed a benefit in only those with elevated homocysteine levels. Those with normal levels showed no benefit. But the bigger question can you lump cognitive decline in those with elevated homocysteine levels as Alzheimer's? Alzheimer's is still mainly a diagnosis of exclusion. My dad was diagnosed with Alzheimer's. He had few of the symptoms other than the inability to recall facts and figures. When my mom finally got him to a pulmonologist who adequately treated his sleep apnea, surprise, his symptoms improved immensely. Older people with memory problems are often given little in the way of alternative diagnosis and relatives must be a real advocate for finding an answer.
Reply | Report Abuse | Link to thisI would love to see a piece on critical thinking in health and science. I've noticed that one major deficiency in mandatory education relates to a lack of self-directed critical thought on the part of students. Most courses are so strongly geared towards rote memorization that critical thought can often be found lacking. Moreover, many individuals learn these skills in a specialized fashion, and may lack the ability to transfer these skills to other areas.
Reply | Report Abuse | Link to thisI believe that it is important for the majority of individuals in a society to be able to understand science in general, and health science in particular. In order to do so, such individuals must have a solid understand of how to navigate misleading, false or logically questionable claims. Recently controversies such as the MMR vaccine link to autism and the multiple sclerosis "miracle cure" are among the more well-known examples of unfounded treatments which have taken hold of the public imagination. Often these controversial issues are worsened by media sensationalism, which compounds the risk that lay individuals will miss a more nuanced explanation for a set of findings.
I would certainly propose a discussion of basic health and science critical thinking strategies. In the area of health in particular, obvious topics would be "the importance of placebo treatment and double-blind controls in health research" or the "limitations of correlational research designs, a primer on causation".
While I have no doubt that most Sci Am readers are better versed in these issues than the general public, I also believe that the public often receives deficient information on how to reason critically. While many publications tend to point out specific examples of non-causal relationships, it seems important that readers be able to parse such information on their own. Perhaps an article on this topic could provide a basic primer on criticism in health research, and then follow up with some real-life examples of controversies in health and medicine and an explanation why such claims go beyond the available evidence.
Hi Christine,
Reply | Report Abuse | Link to thisI would love to see an article about the toxic effects of low-metal poisoning & its relationship to the cause of Alzheimers!
They have known for a very long time that the nerofibulary tangles of tissue that form in the brains of alzheimers patients are forming around cores of aluminum and mercury. This is well documented and the medical field has known it for well over a decade.
There are several books on toxic metal poisoning (most discuss the affect on arterial disease)but I would suggest "Toxic Metal Syndrome: How Metal Poisonings Can Affect Your Brain" by Casdorph/Walker. Their information is supported by medical studies and biochemistry.
The NIH has scientific studies available on their own website about this as well. The NIH has been using this information for drug development. See here ~ http://www.ncbi.nlm.nih.gov/pubmed/11193167. There are some great informative links to other studies on the right side of that page as well.
There are also articles all over online about chelation therapies.
Try here (very informative) ~ http://alzheimers-review.blogspot.com/2010/03/chelation-therapy-for-alzheimer-disease.html
Or here ~ http://www.webmd.com/alzheimers/news/20031215/chelation-therapy-ease-alzheimers
These are reputable websites, although the book I mentioned earlier is more scientific and through in its explanations.
Your article hit home with me as I took care of a close relative with Alzheimer's, and none of his doctors ever suggested chelation as an option even though it has been successfully used as a treatment for over 30 years. Now another person close to me has recently been diagnosed with Alzheimer's as well, without chelation being proposed as a treatment option. This disturbs me a great deal. It takes the patients family to bring chelation up themselves, and not many people are aware of it in order to bring it up in the first place. So I think an article in your magazine could help raise public awareness.
Thank you for your consideration,
Sharon
Thanks, zstansfi. An article on critical thinking is an intriguing idea. Do you know of any new research or interesting investigators in this area? A few years ago Dr. Jerry Groopman wrote a book on How Doctors Think that looked at various cognitive traps physicians (and the rest of us) fall in to. Things like confirmation bias (looking only for evidence that supports an idea as opposed to also considering negative evidence), etc.
Reply | Report Abuse | Link to thisHi Sharon,
Reply | Report Abuse | Link to thisI'm sorry to hear about your personal struggles with loved ones who suffer from Alzheimer's disease. My own grandfather spent the last few years of his life in a nursing home because of his increasing dementia.
Having said that, I'm not sure what we could say about heavy metals and Alzheimer's. A researcher by the name of Markesbery did some definitive work in the 1980s that showed that neither aluminum nor mercury levels are elevated in folks with Alzheimer's compared to those without. But I will take a look at the sites you recommend.
You may also want to check out this site: http://www.kentucky.com/2010/02/01/1119060/william-markesbery-alzheimers.html
Are you part of an Alzheimer caregiver's support group?
Would someone be awesome enough to write a one paragraph summary on this article?!
Reply | Report Abuse | Link to thisThere is a bit of study that says smoking delays dementia....very strange
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I know this is a bit late, but I think my comment still holds.
Reply | Report Abuse | Link to thisThe article is very well written and present very interesting ideas.
The graph on p.38 is however of very limited validity because of the lack on information. Specifically, it is not explained:
- on which time range were the data extrapolated until 2050? If only data from 2008 were used as it seems on the plot, I would really reconsider any extrapolation up to 2050
- where do the data for extrapolation come from (source of the data)?
- on which sample where the data collected: only US citizens, or Europe, Asia and Africa as well?
- and so on.
I don't mean that everything has to be explained in details but I think that most of these important questions can and should be dealt with, even if only with a very short sentence in brackets in the legend.