Can Genetic Risk for Alzheimer's be Reduced?

Contributed by: Dennis Fortier, President, Medical Care Corporation

As genetic testing has become more commonplace in medicine, we have all seen frequent examples of overstatement, where writers and speakers confuse "higher risk" with "absolute certainty".  This has been an especially maddening component of arguments against testing for the APOe4 gene associated with increased risk for Alzheimer's disease.

A great many of these faulty arguments state that learning about a genetic risk for an incurable disease is pointless.  (I have refuted that argument many times but that is not the point of this post).  This week, research published in Archives of Neurology strengthens the case for genetic testing.

In a study from the University of Washington in St. Louis, more than 200 participants aged 45 to 88 reported on their physical exercise habits and submitted to spinal fluid measures or PET scans to determine the amount of accumulated amyloid protein in their brains. They also had their APOe4 status checked and researchers found that, among those who carried the APOe4 gene, regular exercisers had less amyloid load than sedentary members of the group.  Interestingly, this was not the case among the APOe4 non-carriers.

This was a small study and needs replication before we can conclude that physical exercise staves off amyloid accumulation in those with genetic risks for AD.  However, the study has a very intuitive finding and gives credence to a much larger body of work showing that good cardiovascular health may reduce the risk of Alzheimer's disease.

The suggestion from this study is very significant.  It could be that genetic risk for AD (usually considered to be an unmodifiable risk), could possibly be reduced by physical exercise.  If so, it will put a whole new spin on those old arguments against genetic testing.

5 New Alzheimer's Genes: Is This Big News?

Contributed by: Dennis Fortier, President, Medical Care Corporation

This is definitely big news.  But how do you define "big" as it pertains to news?

If you base your opinion on the amount of press coverage devoted to a story, and the prominence of the media outlets covering it, then the recent announcement that researcehrs have discovered 5 new genes associated with Alzheimer's disease is, indeed, "big" news.

However, it is not always clear why a story is big or important, and this often leads to misinterpretations about what a story might mean.  With regard to the 5 new genes, I think the importance lies in the fact that, every new piece of explanatory data can help us understand Alzheimer's disease.

If you read the story and thought it meant that now we can tell who will get AD, you probably read too much into the discovery.  If you thought it meant that we now know how to treat AD, you definitely read too much into the disovery.

AD is a very complex and poorly understood disease.    Scientists have not yet isolated its cause, nor have they clearly mapped the progression of the multiple biological processes that unfold as the disease advances.  There are some consistent elements, like an accumulation of beta-amyloid protein in the brain, and a falling ratio of amyloid/tau proteins in the blood and spinal fluid.  We also generally see shrinkage of certain parts of the brain relative to others, and cognitive decline that usually begins with deficits in short-term memory.

But where it all begins, and which conditions lead to the next, is not clear.  There may be important metabolic processes, chemical changes, immune responses, and inflammatory mechanisms that all play roles in how Alzheimer's progresses.   Finding 5 new genes, with significant correlations to this disease, opens the door to better understanding which of these processes are most likely playing important roles.

To be clear, the better understanding we hope for, will require further work. The thought is that we can figure out what these 5 genes do, and that will tell us which processes might be most important to study as a means of understanding AD.  As you can imagine, that might be a long road.

I think it is great that we have gained new clarity about the possible genetic underpinnings of Alzheimer's disease.  But this is a big news story because it will help us focus future research toward a better understanding of the disease, not because we have unlocked any immediate secrets for better diagnoses or treatments.

Alcohol and Dementia

Contributed by: Dennis Fortier, President, Medical Care Corporation
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Alcohol kills brains cells.  That's an undisputed fact.

So what should we make of the many studies, including a new one published last week in Age and Ageing, that shows a lower incidence of dementia among those who drink light or moderate amounts of alcohol?

First we should note that many earlier studies have suggested similar findings.  In general, cumulative scientific evidence, supporting the same conclusion, builds a compelling case.  In that regard, the findings that alcohol consumption may somehow protect against dementia, should not be lightly dismissed.  After all, part of the scientific discipline is having an open mind when faced with seemingly contradictory evidence.

On the other hand, most recognize that it has been exceedingly difficult to untangle the many confounding factors in these studies.  For example, in this latest publication, the authors found that the subjects who reported themselves to be drinkers, were also higher educated, less likely to be depressed, and less likely to live alone.  All three of those characteristics are correlated with a lower risk for dementia.

This raises the question: are drinking habits and incidence of dementia both related to the same life style choices?  It is plausible that higher educated people partake in better care throughout their lives, and arrive at the age of dementia risk with a lower probability. They might also be more likely to be in good health, have attained the economic status to support an active social life, and have more social opportunities to drink.

In other words, we cannot yet be certain that drinking alcohol leads to lower incidence of dementia.  Perhaps, other factors  cause low dementia incidence AND more social drinking.

Also keep in mind, there are no studies showing that alcohol helps your liver.

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Is Testing for Alzheimer's Ethical?

Contributed by: Dennis Fortier, President, Medical Care Corporation


Regular readers know where the Brain Today blog stands on this one.

We have written many times that the world does not need a single, sweeping answer to the question about whether or not tests should be available to inform people about their future risk for Alzheimer's.  It is a question with as many individual answers as there are individuals on the planet.  Each person is entitled to make that decision for themselves so, of course the tests should be available.  Anyone who doesn't wish to know their risk profile will opt not to learn it.  Those who do wish to know, on the other hand, can do so.

However, the notion of individual rights to make their own decisions has not stopped a growing number of bio-ethicists from debating the topic on a daily basis.  They seek, for some reason, one unified position to which all people should adhere; the single, optimal stance on this complex issue.

In fact, the complexity of the issue is driven by the variability of individual circumstances across a population.  What is best for one person is not best for another.  A fantastic overview of the debate was published yesterday at reason.com.  If this is a topic of interest to you, I encourage you to click through and read it.

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A better understanding and more awareness of Alzheimer's related issues can impact personal health decisions and generate significant impact across a population of aging individuals. Please use the share button below to spread this educational message as widely as possible.

Physical Exercise and Genetic Risk of Alzheimer's Disease

Contributed by: Dennis Fortier, President, Medical Care Corporation
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It has been well established that certain genes confer a higher risk for, but not a certain correlation with, Alzheimer's disease. It has also been well established that physical activity confers many health benefits including better flow of oxygen-rich blood to the brain and higher cognitive function.

Now, a study from the University of Wisconsin, Milwaukee, has looked at the benefits of physical exercise on those subjects with a specific, genetic, predisposition to Alzheimer's. As we would have hoped, the benefits of the physical activity seem to translate to this "at-risk" group as well.

The full publication on this study has not yet been released but the methodology was straight forward. Reearch subjects were separated into a "physically active" group and a "sedentary" group and brain activity was measured with functional MRI. According to the pre-publication press, there was no difference in brain activity in the hippocampul region (where short-term memory is processed) between those with a genetic risk for Alzheimer's and those without it.

This suggests that, even for those with a genetic predisposition to the disease, physical activity might be beneficial in delaying the onset or slowing the progression of Alzheimer's, just as it is for the rest of the population with a more favorable genetic profile.
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A better understanding and more awareness of Alzheimer's related issues can impact personal health decisions and generate significant impact across a population of aging individuals. Please use the share buttons below to spread this educational message as widely as possible.

Another Piece of the Alzheimer's Puzzle

Contributed by: Dennis Fortier, President, Medical Care Corporation
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We know that Alzheimer's is a complex disease encompassing an interactive cascade of pathological processes. Understanding those processes, the mechanisms that trigger them, and beneficial ways to intervene against them, are all topics of intense scientific scrutiny.

This week, that scrutiny uncovered another piece of the puzzle and created a new challenge to understand where and how it fits into the bigger picture.

Research conducted at the University of Miami, and published in PLoS Genetics, showed that variations in the MTHFD1L gene were highly correlated with Alzheimer's disease. In fact, those with a specific variation were about twice as likely to develop Alzheimer's disease as those without it.

This gene also plays a role in regulating the body's level of homocysteine, an amino acid affecting cell metabolism. This discovery seems integral in understanding Alzheimer's because, aside from the high correlation between the genetic variant and the presence of disease noted in this study, high levels of homocysteine were already known to be a risk factor for the Alzheimer's.

As suggested by the headline of this post, this scientific advance provided no new answers; it only uncovered another piece of the puzzle that must be fit into the complete picture before we can fully understand how best to intervene against Alzheimer's. Nonetheless, it is exciting because we cannot hope to fit the puzzle together until all the pieces are in hand, and this is another small but important step toward that end.
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A better understanding and more awareness of Alzheimer's related issues can impact personal health decisions and generate significant impact across a population of aging individuals. Please use the share buttons below to spread this educational message as widely as possible.

Over the Counter Genetics Test for Alzheimer's Disease

Contributed by: Dennis Fortier, President, Medical Care Corporation
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This topic has made for an active news cycle over the past week.

First, Walgreens pharmacies announced their intention to sell an over the counter gene test. The product would enable consumers to swab their cheek and send a DNA sample, via mail, to a lab where the sample would be analyzed. The lab would then report back to the consumer on whether or not the sample indicated an increased genetic predisposition to some 70 diseases and medical conditions, including Alzheimer's disease.

This widely covered story was followed by the news that the FDA had formally notified Pathway Genomics, the manufacturer of the test kit, that the FDA required more information about the product. Finally, the news cycle peaked with Walgreens' announcement that they would not stock the product until the FDA situation was clarified.

The interesting question at the heart of this matter pertains to the debate over the value of providing complex genetic information to the lay public.

Those against enabling people to learn about their genetics take the view that the public must be shielded from information that they might use to hurt themselves in some way. I disagree with those people. Frankly, they remind me of an earlier time when similar thinking suggested that religious scripture should not be translated into common languages for public consumption.

I concede that there is a risk of misinterpretation where some might learn they have increased genetic risk for Alzheimer's disease and falsely conclude they they will definitely get the disease. However, we are talking about a self-selecting population that already has some concerns about their health and has demonstrated a willingness to invest their time, money, and effort into learning more. It is clear that these people want to know.

No one is suggesting we casually thrust genetic information upon anyone who would rather not have it. Those who share my view simply suggest that there is increasing demand among a well-educated public to learn about and manage their own health in a proactive manner. It makes good sense to support them in that noble initiative.


A better understanding and more awareness of Alzheimer's related issues can impact personal health decisions and generate significant impact across a population of aging individuals. Please use the share button below to spread this educational message as widely as possible.

Why is AD More Prevalent Among Minorities?

Contributed by: Dennis Fortier, President, Medical Care Corporation
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With yesterday's release of the Alzheimer's Association's report (2010 Alzheimer's Disease Facts and Figures), one aspect of the report has been greatly emphasized in the press over the past day and a half. I refer to the report's stark conclusion that African-Americans and Hispanics are being especially hard hit.

In fact, according to the report, older African-Americans are about twice as likely as older Whites to have Alzheimer's disease and older Hispanics are about one and a half times as likely. The most obvious conclusion that readers may jump towards is that some genetic difference predisposes risk differently across the human races. However, there is a much better explanation described in more detail by U.S. News and World Report.

Many risk factors play a role in determining the likelihood of any given individual getting Alzheimer's disease. Some of the more well-established risk factors, such as high blood pressure, diabetes, and stroke, are known to be more prevalent in certain populations. There is certainly a correlation between the higher incidence of these risk factors among African-Americans and Hispanics and the incidence of Alzheimer's disease in those populations.

The good news is that these risk factors can be controlled through medical intervention. Theoretically, this should allow us to also reduce the prevalence of Alzheimer's disease in those populations.

Genetic Risk for AD: Important Information to Embrace

Contributed by: Dennis Fortier, President, Medical Care Corporation
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The Washington Post has a health related blog (The Checkup) that often presents interesting viewpoints on a variety of topics. I like reading it and generally find the information useful. Today was not one of those days.

In today's post, the authors argue that it may be better not to know if one is genetically predisposed to higher risk for Alzheimer's disease. As regular readers of this blog already know, that represents a poor understanding of the facts and a position that, for most people, is not in the best interest of health.

Below is the body of the comment I left at "The Checkup".

At the risk of offending the author, it should be noted that "not wanting to know if one is genetically predisposed to Alzheimer's disease" is not a very defensible position once inspected under an educated light.

First, having certain genetic variants (APOe4 or TOM40) may increase risk of one day developing Alzheimer's disease while having a certain others (CTEP) may decrease it. However, no combination of these genes approaches a certainty of fate, they merely suggest probabilities. To imply that learning a bit about one's genetics is akin to knowing the future is to overstate our current understanding of genetics and Alzheimer's disease.

Second, like the author suggested with regards to breast cancer, there is plenty one can do to reduce risks for Alzheimer's (more so than one can do to reduce the risks for breast cancer). For example, there is solid scientific evidence that we should all maintaining good cardio-vascular health (lower LDL's, obesity and BP), enjoy a brain healthy diet (green leafy vegetables, berries, fish with Omega-3's, and fewer fats), remain intellectually and physically active, and stay socially engaged. A few other well supported life-style decisions would be to protect the head against the potential of injury and to stop smoking and excessive drinking. All good advice but perhaps more compelling if one knows they have a high genetic risk for a dementing disorder such as Alzheimer's.

Third, because early stage Alzheimer's has symptoms that look exactly like normal, age-related cognitive decline, it often goes undiagnosed and untreated during its earliest and most treatable stages. If one knows there is an increased genetic risk for the disease, it is more likely that early symptoms will be more vigilantly investigated and medical intervention might occur in a more timely and efficacious manner.

Finally, as other commenters have noted, the problem should be considered in a context broad enough to include more than just the patient. Many other lives are often affected and proper planning can be beneficial to all. The problem of Alzheimer's disease is greatly exacerbated by late detection; a phenomenon that is perpetrated by the antiquated "better not to know" dogma. That may have been true 20 years ago but we need to embrace a higher level of understanding. Journalists who continue to promote that idea are on the wrong side of the solution.

Good Gene, Bad Gene

Contributed by: Dennis Fortier, President, Medical Care Corporation
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It seems like we are often on a quest to identify those genes associated with disease and/or other attributes of poor health and function. However, a well sustained, albeit less publicized, parallel effort is underway to identify genes associated with good health. Researchers from the Albert Einstein College of Medicine have now published in the Journal of the American Medical Association their findings on such a gene.

According to their research, having two copies of a particular CETP variant was highly associated with slower memory decline and general brain health. While this gene variant has long been known to have an association with longevity and with good vascular health, it has never been definitively associated with brain health.

This study confirms what many had hypothesized and represents good news for those with this genetic profile.

One unanswered question, which may be the topic of further study, is how this relates to previous knowledge about the increased risks for Alzheimer's conferred by the APOe4 gene? If both are present (APOe4 and CETP), how does that affect an individual's risk?