When the National Institutes of Health convened a panel of independent experts this past April on how to prevent Alzhei­mer’s disease, the conclusions were pretty grim. The panel determined that “no evidence of even moderate scientific quality” links anything—from herbal or nutritional supplements to prescription medications to social, economic or environmental conditions—with the slightest decrease in the risk of developing Alzheimer’s. Furthermore, the committee argued, there is little credible evidence that you can do anything to delay the kinds of memory problems that are often associated with aging. The researchers’ conclusions made headlines around the world and struck a blow at the many purveyors of “brain boosters,” “memory enhancers” and “cognitive-training software” that advertise their wares on the Web and on television. One of the panel experts later told reporters in a conference call that the group wanted to “dissuade folks from spending extraordinary amounts of money on stuff that doesn’t work.”

But did the panel overstate its case? Some memory and cognition researchers privately grumbled that the conclusions were too negative—particularly with respect to the potential benefits of not smoking, treating high blood pressure and engaging in physical activity. In late September the British Journal of Sports Medicine published a few of these criticisms. As a longtime science journalist, I suspected that this is the kind of instructive controversy—with top-level people taking opposing positions—that often occurs at the leading edge of research. As I spoke with various researchers, I realized that the disagreements signaled newly emerging views of how the brain ages. Investigators are exploring whether they need to look beyond the brain to the heart to understand what happens to nerve cells over the course of decades. In the process, they are uncovering new roles for the cardiovascular system, including ones that go beyond supplying the brain with plenty of oxygen-rich blood. The findings could suggest useful avenues for delaying dementia or less severe memory problems.

Dementia, of course, is a complex biological phenomenon. Although Alzheimer’s is the most common cause of dementia in older adults, it is not the only cause. Other conditions can contribute to dementia as well, says Eric B. Larson, executive director of the Group Health Research Institute in Seattle. For example, physicians have long known that suffering a stroke, in which blood flow to the brain has been interrupted by a clot or a hemorrhage, can lead to dementia. But research over the past few years has documented the importance of very tiny strokes—strokes so small they can be detected only under a microscope after death—as another possible cause for dementia. Studies at autopsy of people who had dementia have detected many of these so-called microvascular infarcts either by themselves or along with the plaques and tangles more typical of Alzheimer’s in the brains of people with dementia. These findings suggest that most dementias, even those caused by Alzheimer’s, are triggered by multiple pathological processes and will require more than one treatment.

Proving that cardiovascular treatment is one of those approaches will take some doing. Just because microinfarcts may make dementia worse does not mean that preventing them will delay the brain’s overall deterioration. Maybe severe dementia makes people more vulnerable to microinfarcts. And just because better control of high blood pressure and increased physical activity seem to decrease a person’s risk of stroke, that does not necessarily mean they are less likely to suffer microinfarcts. Correlation, after all, does not necessarily imply causation. That scientific truism was the problem that kept bothering the panel of outside experts put together by the NIH. Thus, the expert panel concluded, with one exception, that “all existing evidence suggests that antihypertensive treatment results in no cognitive benefit.” Data showing the benefits of boosting physical activity in folks with confirmed memory problems were “preliminary.”

11 Comments

1. 1. Christine Gorman 09:58 AM 11/18/10

   This is the third in our new section on the Science of Health. I'm curious what other topics you think we should cover.
   
   Although 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.

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2. 2. MarkASmith 04:50 PM 11/19/10

   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.
   
   The 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.

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3. 3. jtdwyer 10:57 AM 11/30/10

   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.
   
   I suggest that the long term effects of increased tissue residency of cellular wastes be carefully investigated if they are not already.

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4. 4. jbairddo 12:28 PM 11/30/10

   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.

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5. 5. zstansfi 03:09 AM 12/1/10

   I 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.
   
   I 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.

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6. 6. Sharon 01 in reply to Christine Gorman 08:09 AM 12/1/10

   Hi Christine,
   I 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

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7. 7. Christine Gorman 10:12 AM 12/1/10

   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.

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8. 8. Christine Gorman 10:24 AM 12/1/10

   Hi Sharon,
   
   I'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?
   

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9. 9. comingupwausernameisdumb 12:16 AM 12/6/10

   Would someone be awesome enough to write a one paragraph summary on this article?!

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10. 10. jobsinsales 07:57 AM 1/21/11

    There is a bit of study that says smoking delays dementia....very strange
    <a href="http://salesroles.com/">jobsinsales</a>

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11. 11. glacius 03:47 PM 5/12/11

    I know this is a bit late, but I think my comment still holds.
    
    The 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.

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