On How You Can Melt Your Amyloid for the Price of a Gym Membership

"It is a capital mistake to theorize before you have all the evidence. It biases the judgment."
Sherlock Holmes "A Study in Scarlet"

However, that is exactly how science works. Usually there is a hypothesis that the researcher tries to prove (strangely by trying in fact to fail at disproving it), which informs the collection of experimental data. In the eyes of science, exploratory projects, which in Sherlock Holmes's view would be ideally non-biased, are actually seen as less worthy than traditional hypothesis driven - and as such inherently biased - science.

An interesting case of this scientific conundrum is illustrated by the strange case of how physical exercise (PE) goes after Alzheimer's dementia (AD). In a prior post I discussed some of the ways in which physical exercise might be good for the brain (which you can find HERE).

To summarize, we know that that the brain likes physical exercise. Yet if I may paraphrase Mr. Holmes "What we don't know dear Watson is how it does it."

While it is generally agreed that people who exercise have a lower risk for AD, a cause and effect it is yet to be demonstrated. In other words we don't know if exercise directly decreases the risk of AD, if there is something different about people who are at lower risk for AD that somehow increases their propensity to exercise, or if this is just an indirect effect of decreasing other risk factors for AD (such as diabetes, metabolic disorders, or cardiovascular disorders) or maybe a diffuse effect of an overall improved state of physical health on the brain.

How could we not know?

The problem is that most of the exercise-AD data comes from correlational retrospective studies. For example, at a level of a population, if one compares AD-individuals with non-AD individuals (healthy controls), the healthy people usually have higher levels of physical exercise.

However, when two things happen at the same time it does not mean that one is the cause of the other. No matter how solid, correlation does not necessarily imply causation, and that is one of the major hurdles in interpreting the findings of the PE-AD research.

So I get excited when there is new data that can help us better understand what's at stake here. This is the case with a study that just came out of Washington University looking at how physical exercise affects the amyloid  levels (one of the main culprits in the Alzheimer's drama) in seniors.

But before looking at the study let's talk about a couple of relevant characters in the "Alzheimer and Who Is at Risk for Memory Loss" saga.

First, meet the ApoE-ε4, a genetic factor that's been shown to have the strongest associations with late-onset Alzheimer's. When  ApoE-ε4 is present, conferring the status of (ApoE-ε4) carrier, this distinction comes at the price of a much higher risk for AD.

Second, meet another somber character, a villain with poor boundaries who, like those guests who overstay their welcome, tends to stick around (the ageing brain) for way too long: the amyloid. Clumping up in places where it does not belong, and wreaking havoc wherever it chooses to camp in the brain, the amyloid is the number one on the wanted list for anti-AD interventions at this time. So, when it comes to cognition in the older brain it makes sense to measure the amyloid in whatever way we can (e.g. brain imaging or CSF quotes) and see if we can understand what makes it stay or go.

The Wash U researchers tried to do exactly this. They first determined the ApoE-ε4 status for about 200 cognitively intact subjects, then measured the brain amyloid. They also asked the subjects to complete a questionnaire about the physical exercise history over the last 10 years. Their research question: Can exercise changes one's propensity to store brain amyloid?

What did they find?

ApoE-ε4 brains like exercise or amyloid but not both. If you are a carrier and you don't exercise your amyloid level is up; exercise and you will bring your level down to that of a non-carrier.

However, if you are a non-carrier, your amyloid levels would not change much with exercise. They tend to be low to start with, and they stay about the same regardless of how much time you log in at the gym.

In other words, exercising seems to have sort of a leveling effect on amyloid. Without knowing what your amyloid levels are, and without knowing your ApoE-ε4 status (which might be possible in the future, however is not a routine test your doctor can order for you at this time) the take home point is fairly obvious.

When it comes to amyloid and exercise, there is little to lose and there is a lot to gain. Or, you can think about it this way: exercise and you might just "melt" some of that excessive amyloid that you carry around your brain. Not bad for a cheap and safe treat.

And remember: surfing the net doesn't quite count as as a real sport.

Enough for today: time for you to hit the gym. But before you do, remember to bookmark this page and come back for the next installment of my discussion of this study. Without giving too much away I'll just say that: don't let the fact that this is yet another correlational study stand between you and your exercise routine.

For a summary of this check my Psychology Today blog HERE.

References:

Head D, Bugg JM, Goate AM, Fagan AM, Mintun MA, Benzinger T, Holtzman DM, Morris JC. Exercise Engagement as a Moderator of the Effects of APOE Genotype on Amyloid Deposition. Arch Neurol. 2012 Jan 9. [Epub ahead of print]

© Copyright Adrian Preda, M.D.

Getting to the mind the body-sattva way

I posted Exercising the body is exercising the mind on SharpBrain on August 23rd 2008. To restart the discussion I am re-publishing it now - it should be read together with my previous post. I would like to reopen the discussion and continue it here.

We live in a culture obsessed by appearances where body is many times valued before mind. At the same time, because of this obsession with appearances, the mind partisans uphold, most times, "anti-body" values. It is my opinion that both camps are extreme and as such wrong.

Middle way, as always, is best and this is what I will try to demonstrate in my next few posts on the whole body-mind theme.

Brain Lessons Part 2

I apologize for the long delay in getting back to this column but I have a good excuse. We just recently had a baby boy that takes care right there of the physical exercise need. Between carrying the baby upstairs and downstairs, running to get the baby, getting out of the bed and picking the baby up and putting the baby down a couple of times a night no need to worry about getting my daily exercise dose…

Now, the majority of the answers to my post on the brain virtues of physical exercise suggests that most people think that the brain benefits of physical exercise are mostly to be understood as complementary effects of a healthy life style.

Is this correct? In my post today I will attempt to answer this question.

First, while generally healthier people seem to have healthier brains, the physical exercise effect on the brain seems to be independent of other things. One of the most important development in neuroscience was when the official dogma claiming that there was no neurogenesis (production of new brain cells) in the adult brain was toppled. Now we know that the brain is “plastic” meaning that, under the right circumstances, the brain can change in terms of both producing new cells and getting more cells connected to each other.

One of the places where neurogenesis has been shown to occur in the adult brain is the dentate gyrus, a strip of grey matter placed deep down in the brain. The dentate gyrus is a part of the hippocampus, the main memory structure that has been shown to play a role in the forming of new memories. What can the dentate gyrus teach us with regards to physical exercise?

Following a series of extremely thought provoking experiments researchers from the Gage laboratory at UCSD concluded that exercise leads to the production of new brain cells in the dentate. First the researchers found that mice housed in an enriched environment (a larger cage with toys, tunnels, and more opportunity for physical activity, learning, and social interaction than in standard bare cage) have an increased number of new neurons in the dentate gyrus.

The enriched environment is the mice equivalent of not only healthy but good living: leisurely enjoying life, getting both physical and intellectual stimulation, socializing with friends. Now, the fact that new neurons were produced was a big enough news in itself, but the Gage group did not stop there. Their next goal was to figure out if neurogenesis was the result of a sum of factors acting together (i.e. the enriched environment) versus a specific effect of individual factor. So, they first dissected the enriched environment in a number of “sub” environments. In their next experiment they placed the mice in a “learning environment” where they had access to a maze, a “physical exercise environment” where mice had unlimited access to a running wheel, in addition to enriched and standard (empty cage) environments. Then they compared the groups in terms of behavioral performance and eventually looked at their brains.

Their conclusion was anything but expected: while both enrichment and wheel running led to improved spatial memory function phyical exercise in a running wheel alone also promoted neurogenesis and enhanced the survival of newborn neurons in the dentate gyrus.

Bottom line: exercising seems to literally mean “exercising the brain”.

So, in lieu of conclusion, till next time I wish you all happy trails (and I don’t mean it as just trails on the paper in a paper and pencil memory task)!

© Copyright Adrian Preda, M.D.

Exercising the body is exercising the brain

This is a reposting of one of my original post on Sharpbrains. I posted "The Brain Virtues of Physical Exercise" in August 2008. I just reviewed it today and I found a number of interesting comments that I will discuss on this blog.


So, for a starter, here is the original post. I will follow up with a series of posts discussing the some of the interesting points raised by my commentators.

Brain Lessons Part 1

Let me start with a list of common biases: expensive is better than cheap, free is of dubious value (why would then be free?), rare is likely to be valuable, and while new is better than old, ancient is always best. Which explains a common scenario that is reenacted about twice a week in my office. It starts like this: a patient shows me a fancy looking bottle of the brain supplement of the week: ancient roots with obscure names mixed together in another novel combination which you can exclusively find in that one and only store (rarity oblige!). And not to forget: it ain’t cheap either! Of course, there it is, the perfect the recipe for success: ancient yet new, rare and expensive. It got to be good! But is it, really?

The problem with recommending physical exercise when it comes to brain fitness is that is doesn’t have any of the glamour traits I have just mentioned: it’s been around for a long time – so there is nothing new and exciting about it, there is no fancy name or exclusive label marketing it and, worst of all, it is as cheap as cheap can be: not only free but also available in unlimited supplies.

So when I tell my patients that the single most important thing they need to pay attention to when it comes to keeping their brain in shape is exercise, I invariably get a “really, and you needed to get an MD to tell me this?” look. Nowadays everybody seems to know that physical exercise is good for the brain. Big news they say. And they needed to study that? Duh?

For most it’s no big surprise to find out the people who have a physically active life style have a decreased risk of Alzheimer’s dementia or the number of blocks one walks everyday appears to inversely correlate with the rate of cognitive decline later in life. It sort of makes sense to assume that has to be the case. Here are a few well established facts.

First of all, regular physical exercise correlates with improved health – meaning less risk for high blood pressure, metabolic problems (cholesterol, lipids and glucose dysregulation) and weight gain, which is all good for the brain. A healthy brain needs a healthy environment, doesn’t it? Or to put it in a slightly different way: an unhealthy environment would not be good for the brain, wouldn’t it? I think we would all agree on that one.

Now, would a healthy environment not only protect but also improve the brain structure and performance? Would it also promote the growth (if possible) of the brain? The answers to such questions are less obvious. For example we know that not all healthy people end up with “good brains”. Well, why is that? Specifically, when it comes to physical exercise then, are there such things as a minimal dose of exercise that can result in positive brain effects? And is there a maximal or “toxic” dose of physical exercise, which may in fact hurt the brain? Is all physical exercise equally good for the brain or do different physical exercise routines differ in terms of their brain effects? I put those questions on the table and the chance is that I got the “duh” people’s attention.

First, let me say that to scientists the physical exercise question is no different that any other scientific question. Scientists tend to be a skeptical bunch and as such they like to always point out that correlation does not necessarily imply causation. Take the old active people who didn’t get Alzheimer’s example. One possibility is that their consistent exercising keeps them from getting Alzheimer’s. But what is it that got them to exercise more in the first place? Could it be that their brains were equipped with the sort of gear that gets one excited about pushing oneselve a bit, which would then result in these fellows being more prone towards doing physical things to start with? Then they will be more active physically but that is because their brains were wired differently from the gecko and that, in itself, might have decreased the risk of Alzheimer’s dementia. In a situation like this physical exercise is what scentists call a confounder – i.e. a concomitant but not necessarily casual event that can falsely be seen as a cause resulting in the final effect.

How can one figure this one out? Over the next few columns we will look together at ways of answering apparently not so straightforward questions about physical exercise and the brain.

Now, to begin I will like to make this column, to whatever extent possible, an interactive forum. And that is as it turns out that the brain really likes it when it’s asked to be “active”. Passive audiences, which are spoon fed information, score less well when tested on retention and understanding of the presented material than audiences that were kept engaged through the process. So, in the spirit of “engagement” I will start by asking a few questions about what is important when it comes to the effects of physical exercise on the brain. Depending on what your answers will be we will then take it to the next level, i.e. critically examine the research evidence about specific brain effects of different types of physical exercise.

So, consider which of the following possibilities will get you convinced that physical exercise is good for the brain. Would you be convinced if exercise has been shown to:

1. Increase longevity (as a better brain should make us live longer, shouldn’t it)?

2. Decrease the risk of Alzheimer and other types of dementia?

3. Decrease the risk of “normal” age related memory loss or cognitive decline?

4. Increase one’s ability to problem solve?

5. Decrease one’s risk for depression or anxiety?

6. Improve one’s memory, concentration and attention?

7. Improve one’s ability to feel consistently happy?

8. Increase the number of nerve cells or nerve cells connections in the brain?

9. Correlate with higher education?

10. Correlate with higher social economic status?

11. Chemicals released during exercise were shown to pro¬mote nerve cell growth?

12. Exercise would “correct” chemical abnormalities reported in mental or brain illness?

I am looking forward to your answers. Please do not hesitate to come up with other questions or hypotheses. We’ll make this into an exercise about how to think about physical execise. Another form of exercise that might be good for the brain.

© Copyright Adrian Preda, M.D.