Alzheimer's: Hope on the Horizon

Detection, prevention, treatment, and drug discovery.

Stress, the Brain, Aging and Alzheimer's Disease

Long term effects of stress on the brain

Everyone has been there. You are about to get into an accident, your heart races, your mind is completely focused on the oncoming car, time seems to slow, your thoughts become crystal clear. It's a near-death experience that you never forget. Your "stress response" has helped you to survive.

Here's another scenario: your boss is shouting at you, your kids are sick, bills are piling up, life is getting really stressful on a chronic basis, day after day, and... after a while, you can't think straight! Your mind is racing, you have trouble paying attention and focusing, memory is impaired, worries abound, you can't make decisions or you make bad decisions, and depression may set in. Now the "stress response" is impairing your brain.
What's going on here??

Let's go back to basic biology. Long ago, through evolution, animals developed the "stress response". When a deer encountered a tiger, it needed a "survival response," the "fight or flight response," to either gear up for a fight, or to run fast, pay attention, and then remember where that tiger was, and never go there again. Animals evolved a biological way to accomplish these effects through the stress hormone "cortisol".

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Upon seeing the tiger, the brain recognizes the stress, becomes "dis-stressed," and causes the adrenal glands to secrete cortisol, which turns off all immediately un-needed systems, shuntingblood from the gut (this is no time to eat!) to the muscles and the heart (fight or run fast!). Cortisol also goes directly to the memory and learning centers of the brain (the hippocampus), and to the amygdala (the emotional gateway of the brain for memory). By opening the gateway to memory (the amygdala), Bambi will never forget where that tiger was!
Humans work the same way. That's why when we have a "near-death experience," even though we only experience them once and they are extremely brief, we never forget them.

What happens with chronic stress then? If we are chronically stressed and experience chronic "dis-stress" as a result, then we are constantly releasing cortisol. Like red wine , too much of a good thing can be bad. Chronically high cortisol has been shown to cause brain cell dysfunction, to kill brain cells, and to cause atrophy of the brain. With aging, something additional happens. Biological systems become dysregulated. Our ability to shut down biological systems once they are turned on becomes impaired with aging. Cortisol levels go up, but they stay up longer and go down slower. We become more prone to the psychological effects of stress if we are dis-stressed, and the effects last longer. More brain cells may dysfunction and more may be killed.
Over the course of a lifetime, the effects of chronic stress can accumulate and become a risk factor for cognitive decline and Alzheimer's disease. Several studies have shown that stress, and particularly one's individual way of reacting to stress (the propensity to become "dis-stressed" often found in neurotic people for example), increases the risk for Alzheimer's disease.

So what can be done?

What if we could block the negative effects of stress on the brain with new drugs? Several biotechnology and pharmaceutical companies have tried to do this. For example, a study funded by the Alzheimer's Drug Discovery Foundation attempted to use a drug that blocks cortisol receptors in the brain to treat psychotic depression. Others are trying to find ways to use drugs to prevent and treat the post-traumatic stress syndrome.
Until such drugs are developed, right now the best way to protect your brain from stress is to learn ways to better cope with stress, for example through psychotherapy or exercise, preventing "dis-stress."

Howard Fillit, M.D., is clinical professor of geriatric medicine at The Mount Sinai School of Medicine.

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