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.

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.

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.

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.

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.

Sources and Additional Information:

http://www.myinnerchi.com/health_managing_stress.html

http://helpguide.org/mental/stress_signs.htm

http://www.psychologytoday.com/blog/alzheimers-hope-the-horizon/201003/stress-the-brain-aging-and-alzheimers-disease

http://www.alzheimersreadingroom.com/2011/02/can-stress-cause-alzheimers-disease.html

http://www.kurzweilai.net/how-chronic-stress-causes-alzheimers-other-brain-diseases

http://www.news-medical.net/news/20110728/Chronic-psychological-stress-linked-to-increased-risk-of-Alzheimers.aspx

High Blood Pressure as Risk Factor for Alzheimer’s

Having hypertension, or high blood pressure, reduces blood flow in the brains of adults with Alzheimer's disease, according to a study presented in 2007 at the annual meeting of the Radiological Society of North America.

"While hypertension is not a cause of Alzheimer's disease, our study shows that it is another hit on the brain that increases its vulnerability to the effects of the disease," said study co-author Cyrus Raji, scientist and M.D. and Ph.D. candidate at the University of Pittsburgh where the study was conducted.

Hypertension is a condition in which the blood circulates through the arteries with too much force. According to the National Heart, Lung and Blood Institute, approximately 50 million Americans have hypertension. People with hypertension are at elevated risk for heart attack, stroke and aneurysm. Recently, there has been mounting evidence tying cardiovascular health to brain health.

"This study demonstrates that good vascular health is also good for the brain," said co-author Oscar Lopez, M.D., professor of neurology and psychiatry at the University of Pittsburgh. "Even in people with Alzheimer's disease, it is important to detect and aggressively treat hypertension and also to focus on disease prevention."

For the study, the researchers used arterial spin-labeled magnetic resonance imaging (MRI), which can measure blood flow in the brain, to image 68 older adults. Arterial spin-labeled MRI is a novel, noninvasive technique that requires no external contrast agent.

The patient group included 48 normal individuals, including 38 with hypertension and 10 without; 20 Alzheimer's patients, including 10 with hypertension and 10 without; and 20 adults with mild cognitive impairment, 10 with hypertension and 10 without. Mild cognitive impairment, which affects brain functions such as language, attention and reasoning, is a transition stage between normal aging deficits in the brain and greater levels of dementia.

The MRI results showed that in all patient groups blood flow in the brain was substantially decreased in patients with hypertension compared to those without. Cerebral blood flow was lowest among the Alzheimer's patients with hypertension, but the normal group with hypertension showed significantly lower cerebral blood flow than the normal group without hypertension.

"These results suggest that by changing blood flow to the brain, hypertension--treated or untreated--may contribute to the pathology of Alzheimer's," Raji said.

Among the strongest new studies:

—MRI scans showed women 65 and older with high blood pressure had significantly more white matter lesions in their brains eight years later. The study included 1,403 women who were enrolled in a memory subset of the landmark Women's Health Initiative that tracked postmenopausal health. The worse their blood pressure, the higher volume of white matter damage, says the study published online last month in the Journal of Clinical Hypertension.

“This is a silent disease in the brain,” says lead researcher Dr. Lewis Kuller of the University of Pittsburgh. “It's evolving over time and it leads to very bad outcomes.”

—The journal Stroke just published similar evidence from a Johns Hopkins University-led study that tracked 983 people for more than 15 years, starting in middle age. The longer people spent with uncontrolled high blood pressure, the more white matter damage they accumulated. The researchers could see a change with each 20-point jump in too-high systolic pressure, the top number in a blood-pressure reading.

Clearly, hypertension alone doesn't doom someone to later dementia. Far more people, nearly one in three U.S. adults, have hypertension.

And there are plenty of other reasons to lower blood pressure: Hypertension is a leading cause of heart attacks, strokes and kidney failure.

But while some studies have found hypertension treatment lowered the dementia risk, others haven't.

Enter the NIH's SPRINT study, which has began in 2010, enrolling 7,500 hypertension patients age 55 and older around the country. The test: Whether aggressive treatment to lower systolic blood pressure below 120 — what's considered normal — will prove healthier than today's guidelines that urge getting it below 140, or 130 for diabetics.

The main focus is on heart and kidney health. But all participants will be screened for dementia, and a subset will undergo repeated cognitive testing and MRI scans to tell if lowering blood pressure also protects against a slide toward dementia. Another question: If older patients can tolerate bigger than usual blood pressure drops without side effects, such as falls.

With dementia rising fast as the population grays, even a small effect from better blood pressure control could have a big public health impact, says Dr. William Thies of the Alzheimer's Association.

Other dementia-preventing efforts, such as targeting the sticky amyloid plaques in Alzheimer's patients brains, haven't panned out so far — while hypertension control has little downside, notes Pittsburgh's Kuller.

“Until I can tell you how to get rid of amyloid in your brain, take care of the blood pressure.”

If the high blood pressure in general is more or less proven risk factor for Alzheimer Disease development indentified for the general population, it becomes even more significant when the elderly patients are subject of research. In the current study, researchers from the University of Western Ontario studied 990 older adults, most of whom were in their 80s. All had mild cognitive impairment, which causes problems in thinking and memory, and some had high blood pressure.

Some seniors with mild cognitive impairment have problems primarily with memory, and they are more likely to develop Alzheimer’s disease. Others, including those who suffer a stroke, are more likely to have problems with so-called executive function, which causes problems with making decisions and judgments.

The researchers looked at the seniors for five years. They found that Alzheimer’s disease and other forms of dementia developed in about 60 percent of those who had memory problems, regardless of whether they had high blood pressure or blood pressure that was under control.

But among those with thinking problems but no memory deficits, having high blood pressure was much more likely to lead to dementia. Almost 58 percent of those with thinking problems went on to develop dementia, compared to 28 percent of those whose blood pressure was under control.

High blood pressure is known to damage blood vessels throughout the body, including the brain. Therefore, keeping blood pressure in check may be important for maintaining brain health, especially when the brain may be under assault from other disease processes related to Alzheimer’s.

The researchers concluded that maintaining healthy blood pressure into old age may be critical for lowering the risk of developing Alzheimer’s disease. About a third of seniors with mild cognitive impairment have problems primarily with thinking. “Control of hypertension in this population could decrease by one-half the projected 50-percent five-year rate of progression to dementia,” the researchers concluded.

Sources and Additional Information:

http://www.sciencedaily.com/releases/2007/11/071128114847.htm

http://www.msnbc.msn.com/id/35063248

http://www.chron.com/disp/story.mpl/nation/6834385.html

http://www.alzinfo.org/04/articles/high-blood-pressure-linked-to-alzheimers-in-seniors

Greater purpose in life as weapon against Alzheimer’s Disease

The United States is currently experiencing the early stages of what is expected to be an epidemic of Alzheimer's Dementia. It is predicted that the current number of cases of Alzheimer's Dementia will double by 2020, and double again by 2040. Some unfortunate individuals are born with genes that strongly predispose them to developing Alzheimer's Dementia. However, this is true for only a minority of people. The familial, early onset form of Alzheimer's Dementia, which is so strongly linked to genetic abnormalities, is responsible for about five percent of cases of this illness. There is compelling evidence that the rest of us can escape, or at least postpone or diminish the severity of Alzheimer's, by improving our diets, maintaining our health and generally living healthier lifestyles. In most cases, it appears Alzheimer's Dementia can be avoided.

An underappreciated but scientifically substantiated fact is that getting a good education, challenging your mind, maintaining friendships and staying socially active can also help reduce the risk of developing Alzheimer's Dementia in later life. A new report in the American Medical Association journal, Archives of General Psychiatry, now compliments those findings in showing that simply having a sense of purpose in life can help to reduce this risk.

People who say their lives have a purpose are less likely to develop Alzheimer's disease or its precursor, mild cognitive impairment, a new study suggests. Purpose -- which the researchers define as a "psychological tendency to derive meaning from life's experiences and to possess a sense of intentionality and goal directedness that guides behavior" -- has long been thought to protect against adverse health outcomes. For example, it was recently reported to be associated with longevity, they noted. But there was little information on the association of purpose with Alzheimer's disease.

As the population ages and dementia becomes a more frequent diagnosis, there's increasing impetus to determine the causes of the disease, associated risk factors and how to prevent it, explained study co-author Dr. Aron S. Buchman, an associate professor in the department of neurological sciences at Rush University Medical Center in Chicago.

"There has been a lot of interest in psychosocial factors and their association with cognitive decline and dementia in later life," he said.

The study looked at the positive aspects of life and their possible effect on keeping dementia at bay, "looking at happiness, purposefulness in life, well-being and whether those kind of concepts are associated with a decreased risk of dementia," Buchman explained.

For the study, published in the March issue of the Archives of General Psychiatry, Buchman and his colleagues collected data on 951 older people without dementia who participated in the Rush Memory and Aging Project. The participants were asked to respond to statements such as: "I feel good when I think of what I have done in the past and what I hope to do in the future," and "I have a sense of direction and purpose in life."

After an average four years of follow-up, 16.3% of the people in the study developed Alzheimer's disease. Taking into account other factors that could account for Alzheimer's, the researchers found that people who responded most positively to statements about their lives were the least likely to develop the condition. Also, people who said they had more purposeful lives were less likely to develop mild cognitive impairment and had a slower rate of cognitive decline.

People who scored 4.2 out of 5 on the purpose-in-life measure were about 2.4 times less likely to develop Alzheimer's disease, compared with people who scored 3.0, the study found.

It's not known whether there is a biological reason for this finding, the researchers noted.

"One possibility is that, truly, somebody with high purpose in life might have a lower risk of developing dementia because of what's involved in purpose in life," Buchman said.

"The importance of the study," he added, "is this doesn't prove anything, but it points researchers in the direction of a link between purpose in life and cognition in late life. And now we have to find out what the biological basis is."

Still, the researchers think these findings could have implications for public health. "In particular, these findings may provide a new treatment target for interventions aimed at enhancing health and well-being in older adults. Purpose in life is a potentially modifiable factor that may be increased via specific behavioral strategies that help older persons identify personally meaningful activities and engage in goal-directed behaviors," the authors continue. "Even small behavioral modifications ultimately may translate into an increased sense of intentionality, usefulness and relevance."

"More social activity, more physical activity, higher cognitive activities, high purpose in life -- all these psychosocial factors seem to be linked with longer life, decreased mortality, decreased disability and provide important clues to a public health approach to try to increase independence in older people in later life," Buchman said.

Greg M. Cole, a neuroscientist at the Greater Los Angeles VA Healthcare System, wondered if the study is really measuring depression, not a purposeful life.

"I am unclear about how low scores on the purpose-in-life measures can be separated from mild depression," Cole said. "Depression has been repeatedly associated with increased Alzheimer's disease risk. So psychiatrists can make a distinction, but they seem likely closely related."

"One wonders whether this is a treatable psychiatric condition contributing to risk or an early symptom of decline," he added.

William H. Thies, chief medical and scientific officer at the Alzheimer's Association, said the new study "contributes to the literature that says there is a linkage between behavior and disease."

The study begs the question whether there is more Alzheimer's disease because more people have a lower sense of purpose, or is a lower sense of purpose an early, subtle, sign of dementia, he said.

"As we get better and better at having biological measures of the disease, we will shed a lot of light on these kinds of studies and whether these behaviors are simply a symptom or they are a place where you can intervene," Thies said.

Previous researches have shown that people that have long histories of Major Depression are twice as likely to develop Alzheimer's Dementia than those that do not. Reduction of stress further decreases the likelihood of dementia. Indeed, studies have shown that people who describe themselves as calm, relaxed, and self-satisfied can reduce their risk of Alzheimer's by one half. The East Boston study showed that every year of education after high school reduces the risk of Alzheimer's by 17 percent. A study at Duke University showed that having intellectually challenging work in adult life can reduce the risk of dementia even further beyond what a good education alone can do. In the Honolulu-Asia Aging Study it was found that maintaining friendships in later life significantly improves the likelihood of avoiding dementia. Another interesting study found that people already diagnosed with Alzheimer's Dementia who have large social networks of family and friends can maintain better cognitive function, even with higher levels of amyloid plaque damage in their brains, than can those without such social support. Scientific studies have also shown that people with deeply held religious beliefs and dedication to religious practices, regardless of the type, have a slower rate of cognitive decline when Alzheimer's dementia is already diagnosed. The current study now adds to this list of things we can do and ways we can approach life that can reduce our risk of dementia. Having a sense of purpose in life can reduce this risk.

Sources and Additional Information:

http://www.medicinenet.com/script/main/art.asp?articlekey=113908

http://www.huffingtonpost.com/scott-mendelson-md/a-sense-of-purpose-in-lif_b_488528.html

http://www.sciencedaily.com/releases/2010/03/100301165619.htm

http://abcnews.go.com/Health/AlzheimersNews/purpose-life-stave-off-alzheimers/story?id=9986018