Wednesday, December 28, 2011

Chronic Stress as Risk Factor for Alzheimer’s Disease

Stress is inherent in every human being. It is the way we respond to a real or imaginary threat.  It is the fight-or-flight mechanism which enables our bodies to initiate the chain of biochemical reactions in response to a hazard, whether real or perceived. While your mind and emotions develop through the learning experience of life, instincts were given to you as a survival protection tool.

What is stress?

Stress is a normal physical response to events that make you feel threatened or upset your balance in some way. When you sense danger – whether it’s real or imagined – the body's defenses kick into high gear in a rapid, automatic process known as the “fight-or-flight” reaction, or the stress response.

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When you perceive a threat, your nervous system responds by releasing a flood of stress hormones, including adrenaline and cortisol. These hormones rouse the body for emergency action.

Your heart pounds faster, muscles tighten, blood pressure rises, breath quickens, and your senses become sharper. These physical changes increase your strength and stamina, speed your reaction time, and enhance your focus – preparing you to either fight or flee from the danger at hand.

The stress response is the body’s way of protecting you. When working properly, it helps you stay focused, energetic, and alert. In emergency situations, stress can save your life – giving you extra strength to defend yourself, for example, or spurring you to slam on the brakes to avoid an accident.

The stress response also helps you rise to meet challenges. Stress is what keeps you on your toes during a presentation at work, sharpens your concentration when you’re attempting the game-winning free throw, or drives you to study for an exam when you'd rather be watching TV.

But beyond a certain point, stress stops being helpful and starts causing major damage to your health, your mood, your productivity, your relationships, and your quality of life.

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Chronic Stress Danger

What happens with chronic stress then? If we are chronically stressed and experience chronic distress 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 deregulated. 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 distressed, 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 distressed often found in neurotic people for example), increases the risk for Alzheimer's disease.

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Clinical Research – Stress as Risk Factor for Alzheimer’s Disease

UC San Diego Study, 2010

In 2010, a research group led by Mark Tuszynski at the University of California, San Diego, performed a study on monkeys to see how different environments affect the development of Alzheimer’s disease. Some monkeys were put in very small cages when they were young, while others were in larger cages. The monkeys in the small cages were unable to get enough exercise and released larger amounts of stress hormones. These stress hormones can reduce the number of nerve synapses. Upon study of the monkeys’ brains, it was confirmed that monkeys raised in smaller cages had, on average, a higher density of plaques and lower number of synapses, the same brain pathology seen postmortem in Alzheimer’s patients.

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University of Houston, 2010

In another study in March, 2010, Karim Alkadhi at the University of Houston led a research team to study the effects of stress on rodents in a water maze. Some rats were injected with amyloid peptides, while other rats were subjected to stress by placing an intruder rat in their home cage. The rats were divided into 4 groups to see the effects of the amyloid proteins and stress singly and combined.

The study results showed that only one group of students had difficulty learning the new task, reflecting substantial memory impairment - the animals that received both the amyloid dose and were regularly stressed out.”

Utah State University, 2010

Chronic psychological stress throughout a lifespan might increase an individual's risk for Alzheimer's and dementia later in life, according to research from the Emma Eccles Jones College of Education and Human Services at Utah State University.

The research, led by Maria Norton, Ph.D., built off the recently completed 15-year Cache County Memory Study (CCMS) and used that data to focus on the role psychological stress has on dementia. The findings are consistent with the hypothesis that chronic stress can expose an individual to long-term levels of stress-related hormones, which results in chronically high levels of glucocorticoids, a natural chemical, shown in both animal and human studies to increase the rate of neuronal cell death with long-term exposure.

"Using this objective data, such as death records, medical information, and the cognitive evaluations from the CCMS, we were able to see that people who experienced particularly stressful life events, such as a parent's death during one's childhood, death of a child or spouse, or living with a spouse who is afflicted with dementia is associated with significantly higher rates of dementia later in life," Norton said.

Norton also found that there were some factors that were associated with lower rates of depression and stress, such as individuals who had high levels of religious involvement, thus indicating that the ability to cope with psychological adversity might reduce the risk of Alzheimer's.

University of South California, 2011

While there were multiple studies, which confirmed the causal relationship between chronic stress and Alzheimer’s Disease development, scientists at the University of Southern California (USC) have now found an scientifically backed up mechanism: chronic stress (physical or mental) causes over expression of the RCAN1 gene, in turn leading to neurodegenerative disease.

The mechanism involves the following steps:
  1. In a healthy person, the RCAN1 gene helps cells cope with stress. However, chronic overproduction of RCAN1 causes hyperphosphorylation of tau proteins in the brain.
  2. Tau proteins stabilize microtubules, which are like scaffolding, used to build the brain’s neurons. Previous research has shown that when the tau protein binds too much phosphate (hyperphosphorylation), it forms snarls that prevent the brain’s signals from effectively traveling.
  3. These neurofibrillary tangles eventually choke the life out of neurons, killing off brain function a tiny piece at a time in what is outwardly recognized as degenerative brain disease.

The researchers suggests that overexpression of RCAN1 is also connected to Amyloid beta (overproduction of the Amyloid beta peptide), a competing theory of neurodegeneration.

Further supporting the RCAN1 role are observations that it has been also shown to be chronically overexpressed from birth in the brains of patients with Down syndrome. These patients develop neurofibrillary tangles and typically start to experience the onset of Alzheimer’s disease around age 40.

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