My inbox flooded with links to the report released by NIH (and evangelized by TIME) stating that lifestyle interventions (diet, physical activity, mental exercises, etc.) may not be that effective in preventing Alzheimer’s Disease.

Before I mount my full counterattack, I need to carefully read through the studies the meta-analysis cites.  Still, a quick glance at the exclusion criteria of the meta-analysis reveals the authors limited their review to studies using patients over the age of fifty.  So really, these results imply that lifestyle modifications may not prevent, delay, or treat Alzheimer’s Disease if you start these changes later in life.

My second point is that all lifestyle modifications are not created equal.  Scientific evidence in animal studies suggests that of all interventions, aerobic exercise is our best chance of staving off cognitive decline.  In fact, this meta-analysis also found some correlation between exercise and preserving or improving cognitive ability.

There’s a good article in The Economist that discusses the failures of the drug industry to find a solution to treating Alzheimer’s Disease.  One particular quote resonates with my feelings on the NIH report:

Another fundamental problem is that, whatever is causing the damage, treatment is starting too late. By the time someone presents behavioural symptoms, such as forgetfulness, his brain is already in a significant state of disrepair. Even a “cure” is unlikely to restore lost function.

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I was fairly quiet on the blogs and Twitter the latter part of last week, because I spent Thursday and Friday at the Health Horizons Conference, sponsored by the Institute for the Future (IFTF). I’ll post some reflections soon, but first I want to comment on an interesting discussion that was brewing last week. Read more…

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Ever since I saw the press releases yesterday telling of a new article to be released in Nature showing that brain-training software was ineffective, I knew a storm was brewing.  The paper was still under embargo at that point, so I was anxiously awaiting its release today.  Slowly, but surely, the mainstream media got wind of the paper, running headlines like “Brain Games Don’t Make You Smarter”.  Then the blogosphere lit up, with ongoing chatter throughout the day on this controversial paper.

I was stuck in the lab all day, and couldn’t put a post together, so I’m a little late to the party.  But I wanted to give you a rundown of what exactly the study found, and point out a few intricacies of their findings.

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Check out this study.

Researchers found that when “teenage” rats (30-45 days old) consumed massive amounts of sugar, they became extremely difficult to train as adults. For two weeks or so during adolescence, one group of rats had free access to a tasty 5% sucrose solution, while the control group only had water available. Similar to some American teenagers, the experimental group of rats consumed about 20% of their daily caloric intake as simple sugar.

To give you some background, it’s extremely easy to train adult rats to perform simple tasks, such as pulling levers or pressing buttons in return for a food reward. However, the researchers couldn’t motivate the rats that had consumed large amounts of sugar as teenagers to learn the task. My first reaction while reading this paper was: “Big deal. That group of rats just had sugar overload. It no longer had any real value for them, so there was no incentive to learn the new task”.

But here’s where the story gets interesting: if you repeat the experiment, but replace the teenage rats with adult rats, you get strikingly different results. When adult rats have free access to a sugary drink for two weeks, they never lose motivation for the sweet reward, and easily learn the new lever-pull task later in life. So it’s not that rats are simply sick of the sweet reward, but rather, it seems the sweet drink over-stimulated the reward pathway in the brain during adolescent development, leading to problems with motivation in adulthood.

Were the calories in the sugary drink or the sweet taste to blame for hyper-activating the reward circuits in the brain? To answer this, the authors took another group of teenage rats and gave them free access to a drink flavored with artificial sweetener, which has no calories. These rats were also unmotivated and rather difficult to train later in life, so the authors concluded that the sweet taste, but not the sugar itself, was hyper-activating the brain’s reward circuits.

Besides, ahem, crazy neuroscientists writing for health blogs, who cares about lazy rats? Well, the authors argue that a sign of depression in rodents is lack of motivation to perform simple tasks. Given that incidence rates for depression and other psychological illness are increasing in today’s society, it’s interesting to see how seemingly benign events during adolescence — a critical time in brain development — affect the mental state of adult animals.

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I just finished reading Dave Dobbs’ new article in the the December issue of The Atlantic, “The Science of Success”.  Dobbs turns the classic question of Nature vs. Nurture, whether our genes or our environment are the deterministic drivers of our fate, on its head.  Traditionally, those who support “nature” say that our genes are most influential in defining us.  On the other hand, those that support the “nurture” side say that our environment plays a more important role.

Based on new research, Dobbs introduces the idea of two types of people, “dandelions” and “orchids”.  Dandelions can thrive anywhere, despite their environment or upbringing.  Orchids, however, are more temperamental, and require a stable environment to survive.  At first glance, the orchids may seem like a liability, and in fact, they often carry genes that make them susceptible to mood disorders and psychological disease.  The astounding part of Dobbs’ report is that he shows that given the right care, or environment, the orchids don’t just do OK, but far surpass the dandelions in perfomance.  In other words, given the right training, orchids may in fact be destined for greatness.

This finding redefines conditions we typically may have classified as undesirable.  ADHD, depression, and generalized anxiety disorder, are no longer conditions to dread, because given the right training, people with these predispositions may in fact be the true “movers and shakers” in the world.

Please read the full article for yourself.  And, as always, I’d welcome a discussion here…

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While attending the Institute for the Future’s Health Horizons Fall Conference on Monday, one thing became eminently clear. The 21st century will be the era of brain, the last great scientific frontier. Due to societal shifts, environmental changes, and the fact that we are just living longer, we are poised to see a sharp rise in cases of diseases such as Alzheimer’s, Parkinson’s, autism, and post-traumatic stress disorder. The only thing worse than the increasing prevalence of brain disease is the sobering fact that few viable treatments currently exist.

For years, we’ve heard the mantra of behavior change and health. Exercise more and you’ll cut your risk for heart disease and stroke. Eat more fruits and vegetables and you can decrease your risk for colon cancer (or possibly prostate cancer, as discussed in a previous Decision Tree post, “Why Behavior Change is Better Medicine than Drugs”). Could behavior change serve our brain health as well as it did other organs of the body?

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Usually, we think of preventive medicine as a first-person experience, e.g. what we can do to keep ourselves healthy. But preventive medicine includes steps to keep our families healthy as well, as in the case of an elderly relative, or a newborn baby.

My first postdoc stint was in a developmental neuroscience lab at UCSF, where many talented researchers spent years answering questions like, “How do different types of environmental noise affect the development of the auditory system?”. So when a friend of mine sent me a message the other day, asking about using a white-noise generator to stop her crying, colicky baby, some red flags immediately went off in my head. Because I’ve been asked this question several times over the past few months, I decided to post my take here.

There’s been a lot of anecdotal evidence that white-noise calms a crying baby. In fact, some parents swear by the method. But this is a clear case where the science disproves the hype. In 2003, our lab at UCSF published a study in Science Magazine with a striking finding. The auditory system of newborn rat pups, which normally progresses like clockwork, was under-developed after the pups were exposed to white noise compared to animals raised in normal conditions. But why would white noise cause a problem with the development of the brain?

First, let’s look at what happens to the auditory system during normal development. When rats are born, the area of the brain responsible for making sense of sounds, the auditory cortex, undergoes constant changes. Scientists refer to this phenomenon as brain plasticity. Newborns are unique because brain plasticity occurs just by passive exposure to sounds during a very well-defined time in development called the “critical period”, which lasts through several postnatal days in rats. A correlate in humans might be the fact that children learn new languages just by being exposed to sounds, while adults have to spend hours studying, memorizing, and practicing. This developmental period is a crucial time for a newborn, where the brain “sets” itself to efficiently process its native language.

When white-noise was played for the newborn rats, the lab found that the “critical period” remained open indefinitely, which means there was a delay in normal brain development. For this reason, members of the lab were against using white-noise generators on newborn babies. Theories suggest that the white-noise might interfere with a newborn’s ability to grasp its native language, leading to progressive developmental problems.

Even if the results found in rats did not directly carry over to humans, I really feel that you just shouldn’t screw with Mother Nature when it comes to brain development. I’m not a parent, and I can only imagine the empathy, or even frustration, that ensue when a baby is crying hours on end. But using white-noise generators just doesn’t seem like the best answer. Our brains evolved to process biologically- and socially-relevant sounds, and exposing newborns to extremely unnatural sounds seems like an needless gamble.

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Making a choice that leads to better health is not always easy.  Otherwise, we would have many more ex-smokers and far fewer holiday pounds to shed.  We would have no need for nicotine gum and patches, or Weight Watcher’s meetings.  So if it’s that difficult, why bother?  For years, physicians have told the American public that reducing your calorie intake, eating a diet low in salt/sugar/saturated fat, and exercising 3-5 days per week will reduce your risk for heart disease and diabetes.  Now, new information has shown that the benefits of a healthy lifestyle are even more far reaching than initially thought — diet and exercise can affect our minds.

About 5-8% of people over the age of 65, and nearly 50% of people in their 80′s, show signs of dementia.  As the baby-boomer generation increases the population of the 55-64 age group in the U.S. from 29 to 40 million by 2014 , and their life expectancy continues to rise, the number of people affected by dementia is poised to increase as well.  Recent studies have shown that regular exercise may prove to be a potent mediator of dementia and Alzheimer’s Disease.  In one study, those who exercised 3 or more days per week had a 32% risk reduction in developing dementia compared to those who exercised less.  Exercise has also been linked in similar studies to moderate cognitive improvements in adults who are at risk for Alzheimer’s Disease, as well as a lower occurrence of vascular dementia.

Recent pre-clinical results have shown that diet is also tied to brain health.  A 2002 study revealed that rats fed a diet high in saturated fat and refined sugar for 2 years exhibited changes in both gene expression in the brain, as well as performance on a memory task (finding its way through a water maze).  This fast-food type diet decreased the levels of brain-derived neurotrophic factor (BDNF), which is a versatile molecule that mediates brain cell formation, function, and survival.  Both BDNF gene expression (mRNA) and BDNF protein production in the hippocampus, an area crucial for short-term memory, were significantly reduced in the animals fed the high-fat and refined sugar diet, compared to those on a low-fat, complex carbohydrate diet.  Although the experiment lasted for 2 years, and the greatest effects were seen at the end of the experiment, changes in gene expression were seen in as little as 6 months after the rats began downing cheeseburgers.  Even more striking, the rats had a significant deficit in the water maze memory task after only 3 months on the high fat/sugar diet, which shows that the “McDiet” led to a change in behavior in the mice.

Nevertheless, the research presented here had limitations.  The studies that looked at the effects of exercise on dementia were conducted in relatively small, non-diverse human populations and were not completely controlled against other “good health” factors that tend to occur when people exercise.  For example, exercisers are much more likely to do other healthy things, such as eating right, quitting smoking, getting quality sleep, or maintaining target weight.  The fast-food diet study was well controlled to show that decreased BDNF was not related to hypertension, atherosclerosis, obesity, and changes in activity level — but the results must be taken at face value since it was conducted in rodents, not humans.

So what does all of this mean?  The idea of eating right and getting more exercise is nothing new.  We’ve known for years that changing our health behaviors can stave off heart disease, and potentially let us live longer.  The studies mentioned here really highlight the positive-feedback nature of our actions — behavior changes (diet and exercise) cause physiological and molecular changes in the body, which in turn alter another behavior (memory).  This relationship tells us that our behavior choices no longer only determine life or death, but they also can impact our quality of life.  It’s true that the results don’t make a direct link between diet/exercise and brain health, but rather, a loose correlation between the two that requires further study.  But in my mind, it doesn’t really matter what keeps the brain healthy — my point isn’t that diet and exercise are the end-all cure for disease, but rather, that they are an extremely important part of an overall healthy lifestyle that will allow us to make the most of our golden years.

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