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Stanford Medicine

Aging, Neuroscience

Stanford biostatistician talks about saving your aging brain

Many of us, although we may hate to admit it, occasionally experience forgetfulness, fuzzy thinking, mental fatigue and other signs that our brain is aging. But what, if anything, can be done to maintain mental sharpness?

To find out, I contacted Michael Walker, PhD, a consulting professor at Stanford’s Center for Biomedical Informatics Research. This summer, Walker is teaching a Stanford Continuing Studies course exploring how genetics and lifestyle choices influence cognitive decline and methods for slowing or reversing the process.

In the following Q&A, Walker offers a preview of some of the topics covered in the course, which begins June 22.

What are some of the main reasons our cognitive function declines with age, and how much of it can be prevented?

Genetics plays a role. In the course, I talk about the genetic variants that increase the risk of rapid decline and drugs that are being tested to combat the genes. However, much of the decline is caused by choices we make about food, exercise, supplements, stress and other factors. There is a great deal we can do to prevent or slow cognitive decline.

At the molecular level, we understand many of the factors that cause cognitive decline. These factors include fats that damage or save neurons, damage from free-radicals, loss of nerve synapses due to lack of stimulation, the role of nerve growth factors in maintaining neurons and what things we do that keep up levels of the nerve growth factors. The molecular data show how our choices cause much of the decline.

Previously on Scope, we’ve highlighted research about how meditation may shape the brain. From your experience, how can meditation influence how quickly our brain ages?

The role of meditation is indirect, primarily through stress reduction. A small amount of stress, say from exercise or a novel situation, can be stimulating and good for your brain. Too much stress can be very bad for your brain. Staying in a constant, stress-induced state of “red alert” does all sorts of damage to our bodies. It also does damage to our brains primarily through the stress hormone cortisol.  In the short-term, a small dose of cortisol improves our memory by increasing levels of the neurotransmitter glutamate. Glutamate activates neurons in our hippocampus, a key memory-forming region of the brain.  But in the long-term, high levels of glutamate kill neurons. It overexcites them and burns them out. Excess glutamate is also responsible for brain damage from stroke. Robert Sapolsky, PhD, my colleague at Stanford, wrote “Why Zebras Don’t Get Ulcers“, an outstanding book on stress and stress-related diseases.  Sapolsky’s experiments have shown that high levels of corticoids damage the hippocampus.  Alzheimer’s disease often first appears as damage to the hippocampus.  Alzheimer’s may occur sooner or be made worse by a life of stress.

Another topic that’s been discussed on Scope is the link between physical activity and cognitive function. Can you provide additional insight into how exercise can affect the aging brain?

Your brain recognizes physical activity as a stimulus for your entire brain not just the part required to control movement. When our ancestors were physically active walking around the plains of Africa, they had to use their cognitive skills to predict and recognize danger, to remember or learn where the lions hid, where the best berries can be found, what route is best to get from your find back to camp and so forth. So physical activity tells your brain to get active too.

Exercise protects your aging brain in many ways including producing nerve growth factors (neurotrophins) like nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF). Exercise, NGF and BDNF all increase neuron survival and neurogenesis in the hippocampus. Even going for a walk induces these changes. So when you feel stressed do some physical activity and save your brain.

The stress response evolved to support intense physical activity: fight or flight. It makes sense that a good way to relieve stress is intense physical activity: beat up a pillow, hit a punching bag or go for a run. This is what the stress response is intended to do. So why not do it?

Previous studies have shown that eating berries can boost brain health. How can certain foods slow the brain’s natural aging process?

Three major food choices affect our brain function. The first is total caloric intake, which dramatically affects both lifespan and cognitive decline. In animal studies, for every 2 percent reduction in total calories, we see about a 1 percent to 2 percent extension of lifespan. So reducing calories by 20 percent gives about a 10 percent to 20 percent extension in lifespan. There is a limit: 100 percent reduction doesn’t work. Up to 50 percent calorie reduction appears to extend lifespan.  In the island of Okinawa in Japan, more people live to over 100 years of age than anywhere else in the world. Their rates of stroke, cancer, dementia and other age-associated diseases are among the lowest in the world. Why? While many factors may contribute, caloric restriction appears to be one of the most important. In the course, we’ll look at effective ways to reduce caloric intake.

The second is the type of fat we eat. The type and amount of fat you eat determines:

  • The number of dendrites and synapses in your neurons
  • The type and amount of neurotransmitters your neurons produce
  • Your ability to learn
  • Your mood
  • Your risk of stroke, Alzheimer’s disease and Parkinson’s disease

Good fats (polyunsaturated fats such as omega-3 fatty acids) are major components of our neural synapses and the mitochondria that produce the energy our neurons need. Insufficient omega-3 can contribute to loss of cognitive abilities as well as to early death from heart disease. Saturated fats and hydrogenated fats are bad for your brain.

Carol Greenwood, PhD, at the University of Toronto has studied the effects of fat on the brain.  In one set of experiments, Dr. Greenwood fed rats diets containing up to 10 percent saturated fat and tested their learning ability. The result: The rats’ ability to learn fell directly with the amount of saturated fat in the diet. For rats on a diet of 10 percent saturated fat, their learning ability was near zero. The average saturated fat in Americans diets? About 11 percent.

The third food choices with major effects on our brain function are the antioxidants. This is where berries come in. Many studies in animals show that high levels of anti-oxidants can greatly extend lifespan and maintain cognitive function. However, for humans, achieving these benefits probably requires more antioxidants that we get from food sources. In the course, we’ll talk about which supplementary sources are effective.

Your course examines potential future treatments to slow or reverse brain aging. What areas of research are showing promising results and how far out are these types of treatments?

Some new treatments are in clinical trials now such as drugs to improve memory or slow cognitive decline and a new treatment for stroke that pumps laser energy into the mitochondria to save neurons. We’ll take a closer look at those in the course.

Much of the research on anti-aging applies directly to slowing brain aging. Understanding the mechanisms by which caloric restriction and antioxidant therapy slow aging is giving us new potential targets for treatment and prevention, and identifying the most effective interventions.

Our greatly increased understanding of the genetics of aging and cognitive decline gives us many new targets for treatments to slow or reverse these effects.

Further out in time are stem cell treatments for diseases such as Alzheimer’s and Parkinson’s. But stem cell clinical trials in humans to treat nerve damage in spinal cord injuries are now under way. Clinical trials using nerve growth factors to treat Alzheimer’s and Parkinson’s are also ongoing.  We are making amazing progress in understanding aging and cognition and what we can do to slow or prevent it.

Previously: Researchers working to improve Alzheimer’s detection Mental illness becoming more common in the elderly, warn researchers The long good-bye: Stanford expert discusses Alzheimer’s in new podcast and Alzheimer’s disease costs to soar over next 40 years

Photo by Wellcome Trust

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