By Paul R. Burghardt & Simon J. Evans

In the last article we spoke about the age at which a person develops diabetes increases their risk for different types of dementia. In effect, the longer you can hold-off developing diabetes the less risk you have for developing vascular dementia and Alzheimer’s Disease.

A recent article by De Felice and colleagues in the Proceedings of the National Academy of Sciences speaks to how preventing diabetes or effectively managing the disease can affect brain cells at the microscopic level.

In this study, the researchers were able to show that insulin blocks the protein A-derived diffusible ligand (ADDL). This protein causes all sorts of problems for neurons including withering of the “spines” that make connections with other neurons and redistribution of other neuronal components (receptors) that are critical for the formation of memories.

In a sense, it appears that insulin is helping neurons stick to a microscopic version of the “use it or lose it” principle. When insulin was able to interact (bind to) insulin receptors the ADDL protein was not able to bind to the nerve cells. If you don’t use your insulin receptors, you lose parts of your brain cells (i.e. spines).

One issue that needs to be pointed out regarding this paper is that these studies were carried out in “cell culture.” No, this is not a New-Wave band from the 80’s. Cell culture, in science at lease, refers to a technique used to grow cells in a dish. Once you have cells growing in this very controlled laboratory situation, you can test the effects of different drugs, chemicals, nutrients on various functions of those cells. This is great for learning about how the nuts and bolts of cell biology work, however this is not a “natural” situation for a cell, and it can be difficult to directly use the information gleaned from cell culture experiments in an intact organism (i.e. a walking talking human).

With that cautionary point about cell culture experiments in mind, we’d like to point out that there are studies showing that insulin-sensitizing drugs (drugs that help the body use insulin) can improve memory in diabetics and people with Alzheimer’s Disease. So this is something that people should pay attention to! Not just us nerdy scientists that are fascinated by how things work under a microscope.

The real take-home message for diabetics, relating to the previous blog, is that good management of your diabetes is EXTREMELY important. If insulin has the ability to block these nasty little ADDL proteins from eating the branches of your brain cells, then the better control of your insulin levels should help you fend off these proteins. If you are not diabetic, but have a family history, then take steps to reduce your risk of developing diabetes. This disease occurs over time, so the longer you can avoid it (see the February 17th blog) the less you are likely to accrue.

Now, if you’ve been reading faithfully, you’ll notice Simon focused on the same article in “Control your blood sugar, Improve your memory?” on February 11th, but we wanted to revisit it to tie together with the posted on February 17th, “Diabetes increases risk for developing dementia: what control do you have” to emphasize that no matter if you have ‘normal’ blood glucose control or have diabetes you can help reduce your risk for developing dementia.

Another side-note….although the narrator of the video clip below mentions that insulin does not cross the blood brain barrier (which protects the brain from bad stuff), there is pretty good evidence indicating that insulin actually does cross into the brain.

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By Paul R. Burghardt

A recent report by Xu and colleagues in the journal Diabetes, addresses one of the “modifiable risk-factors” for developing dementia. In other words, it tried to identify those things we do and control on a day-to-day basis that ultimately reduce or increase the likelihood of developing disease. These modifiable risk-factors include things like weight-management, blood pressure control, managing diabetes, and exercise. This study focused on how diabetes can influence the chances that we develop dementia depending upon genetic traits and when in the lifespan a person develops diabetes.

Since diabetes increases the risk of developing Alzheimer’s disease, as well as vascular dementia (yep, unfortunately there are a couple of ways to develop substantial cognitive decline), understanding how genetics and lifestyle choices interact during the development of disease will provide a lot of information that can be used for both prevention and treatment. We already know that avoiding diabetes, or managing diabetes effectively, is of the utmost importance.

To address the issue of how the development of diabetes relates to the risk for dementia, Xu and colleagues utilized the Swedish Twin Registry. This is a national survey in Sweden that tracks health information about twins, which is pretty cool for research purposes. Plus, it’s good to know the Doublemint girls are keeping busy, right?

Their general findings weren’t too surprising: diabetes increases the risk for developing dementia whether it be, vascular dementia or Alzheimer’s disease. However, there were some distinct findings in this study emphasizing that timing is everything.

A particularly interesting finding was that the risk for dementia (vascular or Alzheimer’s disease) increased if a person developed diabetes before they turned 65. By the way, the most common time for Alzheimer’s disease diagnoses is in people 65 years of age or older. Remember, this disease takes a number of years to develop, so what you do now may have a substantial impact on how your brain ages.

This probably occurs by the amount of ‘wear-and-tear’ your brain is able to handle under diabetic conditions, particularly if you are genetically predisposed to developing dementia. The concept of cumulative wear-and-tear has a fancy name, “allostatic load.” This idea is important for all aspects of our health as it accounts for the interactions between our genes and environment in a time-dependent manner. But that is for another post….

In general, this study reiterates a couple of issues. First, it highlights the importance of the mind-body link. Although many people think that diabetes is a problem for blood sugar control, it influences a lot of other organs in our bodies, including our brains. Second, if you have a family history of diabetes the longer you avoid developing the disease the better this will be for your brain (and rest of your body).

Unfortunately in this study the authors weren’t able to look at individual’s ability to control/manage their diabetes. But I’d like to be optimistic and believe that better management of a disease like diabetes would help decrease its negative influence on other aspects of our biology. In line with this, please see our blog post for this Thursday!

Reference:
Diabetes. 2009 Jan;58(1):71-7. Epub 2008 Oct 24.

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By Simon J. Evans, PhD

It’s been long known that social support is good for your health, and conversely, social isolation can put you at increased risk for many diseases. Having a good group of friends and family can protect from heart disease, Alzheimer’s disease and generally leads to longer life.

Part of this is related to the ability to handle stress, having a shoulder to lean on and such. The ability to express your feelings to others has a calming effect on your nerves and actually helps your regulate the hormones that control your physical stress responses.

Part is also due to the tendency to take a little better care of yourself with others around. People who live alone aren’t as motivated to cook healthy meals for one. If you are married and your spouse (and maybe kids) have left town for a few days, you probably don’t eat quite as well as you do when they’re around. But this is only part of the story and there is much that we have yet to understand.

A new small study published in the September 2008 edition of Molecular Psychiatry adds some interesting insight. The study was done using mice. After all, mice are social animals as well, who live in groups referred to as a horde or mischief. The authors found that mice housed alone have a much more difficult time recovering from a heart attack than those housed with other mice.

Since, in this study, the mice were all fed the same thing and treated the same by the researchers, the only difference was their ability to interact with other mice. This controls for many of the differences in people’s lives that are impossible to control for in human studies.

The researchers looked at brains and stress levels (by hormone responses) of mice that were housed with four other mice or by themselves, following a non-fatal heart attack event. After the heart attack, the mice were resuscitated in much the same way we would be, by adrenal injections and mouse-sized CPR. They found that those that lived with other mice were much better off and were somewhat protected from the damaging effect of the heart attack.

The socially housed mice had far less brain damage (due to temporary loss of blood supply to the brain) and lower stress hormones after the heart attack than did those who had no social support. Interestingly, the part of the brain that these researchers looked at was the hippocampus, which we have discussed before as crucial for learning and memory. It is also one part that seems to degenerate during Alzheimer’s disease. So this research suggests that social support can help protect this crucial part of the brain from a serious environmental insult; in this case, a heart attack.

So when you’re visiting your family over the holiday season, be grateful for the support you have. Even though they may stress you out sometimes, you know that in times of need they would be there for you. This alone is a key factor in brain fitness.

Reference:
Molecular Psychiatry (2008) 13, 913-915.

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by Simon J. Evans, PhD

There’s a rapidly emerging research field centered around ‘epigenetics’. Essentially, this is the ability to modify your genes during your life to change their level of activity. Genes, in and of themselves, are just blueprints. In order to use them you have to make the product that the genes code for. This requires ‘activating’ the gene so that it goes into production mode.

Epigenetics refers to the types of modifications we do to our genes that either crank up their productivity or dial it way down. The kicker is that these types of modifications can be heritable. Meaning, the way you modify genes during your life can be passed on to future generations. Also, the way your parents and grandparents modified their genes may have been passed on to you.

So far, we know that this applies to genes that control your eating behavior, fat storage, learning and memory, predisposition to drug addiction, and your circadian rhythms. Epigenetics have also been implicated in the risk for diseases such as schizophrenia, bipolar disorder, and maybe even Alzheimer’s, so definitely fall into the realm of keeping your brain fit.

So how do we modify our genes? This is a hot area of research. We have made great strides in understanding of how our genes are modified at the biochemical level, but we are still only scratching the surface of understanding which behaviors or experiences cause these modifications.

However, current research does support the role for a few major lifestyle factors. First, what we decide to eat can have an effect on how our genes are modified. Certainly, pregnant women partially control the modification of their unborn’s genes through dietary choices. But there is also data suggesting men’s diets can control the epigenetic modifications of their future kids and even grandkids. Second, stress levels and trauma exposure are likely to be key factors in controlling epigenetic modifications.

Okay. So the way we choose to live our lives can modify our genes and we can pass those modifications on to our next generations. But what kinds of effects are we talking about?

Again, the field is young, but there are some interesting studies out there. A new study from Chang et al. at Rockefeller University published in the Journal of Neuroscience, used rodents to show that a mother’s diet during pregnancy continues to effect their offspring well after birth. Not too surprising, but here are some interesting details.

Moms who ate a high fat diet had babies, who, after birth, showed a preference for fat (over carbohydrates), ate more when allowed to eat freely, and showed an increase in many hormones that make you feel hungry. This included hormones released from the gut and those controlling feeding behavior at the level of your brain. Not surprisingly, these baby rats grew up to be fatter teens (they didn’t follow them into later adulthood) and had higher triglycerides and higher insulin. In humans, these types of changes can link to increased risk for diabetes, heart disease and depression.

To be clear, this study was solely about mom’s diet. There were control rats, who were genetically very similar, that ate a balanced diet and their pups did not have these problems. This means that the high fat diet that mom ate caused epigenetic changes in the pups that cranked up the production of genes the led to bad dietary choices in the pups, even after mom was out of the picture.

There are a few interesting studies in humans as well that suggest these types of effects apply to us as much as our lab rat friends. And it’s not just the mother’s diet that counts, although that probably has the biggest effect. Another study found that paternal grandfathers who suffered from a famine, had grandkids with a higher risk for diabetes.

So to answer the question posed in the title of this article, yes and no. You are probably stuck with the genes you’re born with, but how you choose to use those genes (and pass them on to your children) depends on how you choose to live. Even if you are past your reproductive years, the behaviors that you instill in your kids and grandkids can alter their genes and their future generations, so why not alter them for the better?

References:
The Journal of Neuroscience (2008), 28(46):11753-11759.
The Journal of Neuroscience (2008), 28(46):12107-12119.

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By Simon J. Evans, PhD

The title question may be a bit of a stretch, but you only need to connect a couple of research dots to get from childhood obesity to reduced brain fitness in older age.

Belly Fat and Brain Fitness are Related

First, a recent meta-analysis from researchers at Johns Hopkins University verified that the odds of getting Alzheimer’s and other types of dementia increase as you gain weight. A meta analysis takes all previous studies on a particular topic and looks at them together to improve the statistical power over any one study by itself. This particular meta analysis looked at all studies that evaluated whether or not risk for Alzheimer’s or other types of dementia is increased in obese individuals.

Some studies evaluated obesity status of people in their mid-forties, others looked at people in their mid-sixties or seventies. In any case, obesity in mid-life or late life increased odds of getting Alzheimer’s disease or other dementias anywhere from 10 to 30 years later. Importantly, researchers controlled for socio-economic status, lifestyle choices, genetic factors and other illnesses so that the condition of obesity itself, seemed to be the culprit.

Adolescent Weight Problems Lead to Adult Weight Problems

The second dot to connect is that being overweight in childhood dramatically increases the odds of battling a weight problem throughout adulthood. So giving in to your kids’ demands for cakes, cookies and sugared cereals now, is not doing them any favors down the road.

There are really two ways to pack on the pounds. One is to make more fat cells, and the second is to store more fat in the fat cells you already have. An important study from the Karolinska Institute in Sweden, discovered that the number of fat cells you will carry throughout your adult life is really set during your adolescent years. After the age of 20, your number of fat cells will stay about constant.

Obviously, this doesn’t mean that your weight is set after age 20. You can still lose weight or dramatically gain weight. It’s not uncommon to gain weight in your 30s and 40s, as your activity level and metabolism slow down, especially if your food intake doesn’t change. You can always lose or gain fat in the cells that you already have. However, if you gain too much weight in adolescence, when you are actively making more fat cells, you are going to set yourself up for a tough battle for the rest of your life. So as parents, we should do everything possible to regulate our kids weight while it’s still somewhat in our control.

If you connect these two lines of research, you can see that increased weight gain in childhood predicts increased obesity in adulthood; and increased obesity in adulthood boosts your odds of Alzheimer’s and dementia in your 70s and 80s. There have not been any research studies following kids all the way from adolescence to old age to look directly at the relationship between childhood weight and dementia, but they will come eventually. Personally, I won’t be surprised if these studies find increased odds of dementia with childhood obesity.

It’s difficult to think of our kids as old people, but that is who they will become. We must think proactively and do everything we can to boost their odds of life-long cognitive success. If you have concerns about your own children’s weight, work with your pediatrician to design a diet and exercise program and get it under control while you still can. If you struggle with a weight problem yourself, don’t give up. The more effort you put in to bringing your weight under control, the better your odds of a fit brain down the road. Even if you only drop some of the weight you want to lose, every little bit helps boost those odds.

References:

Nature (2008) Jun, 453(7196):783-7

Obesity Reviews (2008) May, 9(3):204-18

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By Simon J. Evans, PhD

Does your job have anything to do with your odds of getting Alzheimer’s disease down the road? Studies have come out recently linking intellectually challenging careers to reduced risk of dementia. Other studies link education level to cognitive health in later years. Overall, people with more education have lower rates of Alzheimer’s disease than those with less education.

This really isn’t that surprising if you think about it. We know that the more you use your brain, the stronger it gets. Just like muscles in your arms and legs, the brain gets more fit when you work it out. Higher education usually means more mentally stimulating jobs and that keeps your brain fit.

But that doesn’t mean that you have to go to graduate school to stay mentally active. Big studies look at large groups of people. On average, when you look at lots of people those with higher levels of education have more intellectually challenging jobs. So overall, they have lower rates of dementia. However, you can be a high-school drop out and still do what’s necessary to keep your brain fit. Just don’t be average.

You can maintain an active mind by committing yourself to life-long learning. It doesn’t take a formal education to teach yourself new skills, read new books and continually challenge your mind – it ain’t rocket science.

There is, however, a flip-side to this coin. Even though higher education predicts lower odds of getting Alzheimer’s disease, those with higher education who do get Alzheimer’s, decline much more rapidly and die sooner than those with less education. Remember, again, this is based on big number averages and is not necessarily predictive for any one person. Still, on average if you have an intellectually challenging career, your odds of getting dementia are lower, but if you do get it, your odds of rapid decline are greater.

At first, this might seem paradoxical. But I think there is a likely explanation for these seemingly odd data. It all relates back to the cognitive reserve theory, which we have discussed in the past.

Essentially, cognitive reserve is something you create throughout your life. The more you learn and the more you experience, the more you create cognitive reserve. This is like ‘extra’ brain circuits to accomplish intellectual tasks.

Think of it like a city building multiple bridges across a river. If you only have one bridge to cross the river and it gets knocked out by a freak storm, you can’t get traffic to the other side. If, however, you’ve created reserve routes to cross the river with multiple bridges and one gets knocked out, you can divert traffic across the other bridges.

This is the same with brain circuits. If you’ve created multiple circuits through a variety of experiences you have different ways to accomplish the same task. If one takes a hit due to age-related damage, you can divert thoughts through different circuits and not really notice a problem.

So people with higher education and more challenging jobs may have reserve brain circuits. That means that even though we may all experience the same age-related damage, someone with more cognitive reserve will show less cognitive decline. There are also ways to minimize the age-related damage through healthy living, but that’s another topic.

So why would people with more reserve show more rapid decline once dementia sets in? Again, this makes sense if you think about it. People with high levels of reserve who get dementia must have experienced severe damage that took out all their bridges. Damage of this severity will take them down quickly.

However, it’s an illusion. Since studies only compare people diagnosed with dementia, they may be comparing apples to oranges. On average, the people with high reserve (mentally challenging careers in these studies) who have Alzheimer’s disease have likely experienced a lot more damage than, on average, the people with low reserve who have Alzheimer’s.

This would explain why people with more challenging careers would have fewer cases of Alzheimer’s; and also why people with higher levels of education who do get Alzheimer’s, decline much more quickly.

Overall, it’s better to boost your odds of not getting dementia in the first place by doing what’s necessary to challenge your mind on a daily basis. Commit yourself to life-long learning and stay mentally active to build more bridges. Couple this with quality nutrition, plenty of exercise and enough sleep, and you will also minimize the storms that create the damage that can damage your bridges.

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