STRESS IS NOT REALLY NERVOUS TENSION, SO WE will not dwell on the subject of nervousness and chronic anxiety, the cause of which must be determined and removed. Damaging or unpleasant stress, as Hans Selye states, is ‘‘stress with distress and this is always disagreeable.’’ Although stress can be associated with pleasant situations, it is more often produced by unpleasant stimuli. the word ‘‘stress’’ is derived from the old French and Middle English words for ‘‘distress’’; the first syllable was lost over the years.

I. EFFECTS ON THE CARDIOVASCULAR SYSTEM

There is no doubt that stress is awful. With the exception of severe pain and death, severe stress with distress is one of

the most difficult situations we have to face. Stress produces well-known reactions in the body such as an increase in blood pressure which causes small blood particles (platelets) to become sticky. the platelet particles stick together to form clumps or sludge, which can lead to formation of a blood clot in the coronary artery.

Trauma to arteries wreaks havoc like a silent killer. during the stress reaction, the arteries constrict under the influence of adrenaline and noradrenaline (epinephrine and norepinephrine). consequently both systolic and diastolic blood pressure increase. If the baseline blood pressure is usually 120/80, it can go up to 160/90 or from 145/95 to as high as 210/110. these elevated pressures, lasting only minutes, are injurious to the arteries, and when combined with the effects of excess adrenaline causing platelet sludging in the arteries, the death toll from heart attacks increases.

How does stress cause heart pain (angina) and damage to the heart and arteries? when the coronary arteries are narrowed by plaques of atheroma, chest pain may occur (see the chapter Angina). Chest pain is made worse by exertion such as walking up a hill. Pain at rest may occur, however, if the patient faces sudden emotional upset.

Stress causes adrenaline and noradrenaline release. these stress hormones cause the heart rate and blood pressure to increase, giving the heart more work to do (see Fig. 1). in some patients, adrenaline may cause platelets to clump onto plaques of atheroma, thus causing oxygen lack to that segment of heart muscle. this oxygen lack may or may not produce chest pain.

Moderate stress associated with simple daily activities can decrease the blood supply to the heart muscle in patients with coronary heart disease. in a study of 16 patients who had angina, the moderate stress of mental arithmetic caused oxygen lack to the heart muscle (myocardial ischemia) similar to that produced by exercise (see Fig. 2). in these patients a radioisotope material (rubidium-82) was injected into a vein, and when it reached the heart muscle photographs were taken. the dark areas in Fig. 2 represent the uptake of blood supply to the heart muscle. when the supply of blood is decreased, the area of muscle is poorly supplied with

blood, the presence of the rubidium-82 is reduced, and the area of darkness is diminished.

In a similar experiment, a patient who was having catheterization of his heart (coronary arteriogram) was asked to do mental arithmetic, asked to think of a past stressful situation, and saw the result of his catheter studies. His heart muscle function was determined during the test and showed no significant change with thinking of past stress, but showed a mild defect during mental arithmetic and severe defects in muscle function during the explanation and viewing of the findings of his heart catheter test.

A stressful situation causes the ‘‘emotional center’’ in the brain to trigger certain reactions (Fig. 1). the hypothala-mus sends signals to the pituitary gland and sympathetic nervous system, which lead to secretion of the ‘‘stress hormones’’ cortisone, adrenaline, and noradrenaline. Cortisone causes an increase in blood glucose and an increase in blood pressure.

As a result of a stressful situation (stressor), the inner compartment of the adrenal glands pours out adrenaline and noradrenaline and these compounds are involved in the ‘‘fight or flight’’ reaction. the external stimulus (stressor) is usually a condition that produces anger, fear, anxiety, and deprivation. Common stressors include the

death of a spouse, conflicts with others, and projects requiring a deadline. very often the stressor consists of words that are interpreted by the individual as harsh or hurtful, resulting in anger, hostility, humiliation, or resentment.

The body reacts in the same way regardless of the type or source of stress or unexpressed anger. Stress from an argument with the boss, fellow workers, a spouse, or others is the same as stress from being chased by an assailant. the fight for so-called prestige, recognition, and survival at work or at home goes on daily, and for many years you may bear the brunt of the stress.

When an individual is riled to the point of bursting, adrenaline in excess has been poured into the circulating blood. Visualize the adrenaline as little death potions that one may drink at work and for some, unfortunately, at home. Adrenaline is helpful in some situations; for example, when you want to flee from a charging bull or an assailant. these compounds increase the heart rate and blood pressure and increase the supply of blood containing glucose and oxygen to exercising muscles so that you are able to run. an excess of adrenaline and noradrenaline can be dangerous because these chemicals can over-stimulate the heart, disturb its electrical stability and, on rare occasions, lead to ventricular fibrillation.

Adrenaline causes a decrease in the ventricular fibrillation threshold and can precipitate ventricular fibrillation and cardiac arrest. Adrenaline causes platelets to clump, and if this occurs on a plaque of atheroma, pain can occur or a clot can develop. these compounds can also cause spasm of the coronary arteries, which in turn can produce chest pain and sometimes death, especially if the spasm occurs where the plaque partially blocks the artery.

Heart deaths are due to two major problems: (1) formation of a blood clot at the site of partial blockage by atherosclerosis in a coronary artery and (2) electrical disturbances that cause the heart to quiver and not contract (ventricular fibrillation). Sudden death is common, and the possibility cannot be excluded that severe acute stress may cause death by initiating a brain-adrenaline-heart interaction (see Fig. 1). the clumping of platelets can enlarge the plaque, and over a period of years the buildup of clot on a plaque can cause complete obstruction of the artery. Animal experiments lend support to this hypothesis. Rats exposed to sudden trauma develop blockage of the coronary arteries, which results in damage to the segments of the heart muscle (myocardial infarction). when rats were not physically traumatized but were stressed with nonphysical traumatic electric shocks, they developed clots in the coronary arteries and died. when rats were pretreated with drugs that prevented platelet clumping, such as aspirin or dipyridamole, and then

subjected to similar electric shocks, clots were prevented in the majority. If rats are pretreated with a beta-blocker, which blocks the dangerous effects of adrenaline, ventricular fibrillation is prevented and rats survive.

Experimentally, adrenaline or noradrenaline given intravenously can cause severe electrical disturbances and ventricular fibrillation. during a heart attack, there is an increase in noradrenaline in the heart muscle. when blood flow to the heart is reduced by atherosclerosis of the coronary artery, severe stress can more easily precipitate ventricular fibrillation.

When a coronary artery is suddenly blocked in dogs, severe quivering of the heart occurs in some. when the hypothalamus (in the brain) and sympathetic nervous systems are stimulated to produce noradrenaline at the same time that the coronary artery is blocked, quivering of the heart frequently occurs. Beta-blocking drugs block the actions of adrenaline and noradrenaline, and if dogs are pretreated with these drugs and the coronary artery is then blocked, the dangerous quivering of the heart can be prevented.

In a study involving 117 patients who were resuscitated from cardiac arrest, 25 reported that they had severe stress such as job and family conflicts within the 24 h prior to the cardiac arrest. Acute or prolonged (chronic) stress may produce severe damage to the coronary arteries. it must be remembered that atheroma of the arteries commonly produces no symptoms; it is a silent killer and after many years, a clot can develop on a ruptured atheromatous plaque. There is considerable evidence linking increased stickiness of platelets to the production of atheroma and blockage of arteries.

A. Stress and Sports

Do not push yourself excessively during a run if you are not a trained athlete. Do it if you feel great and enjoy it, and do not have to clench your jaws or tighten your facial muscles. If you have to push yourself to do an additional mile, then you may secrete excess adrenaline and noradrenaline and this takes its toll on your cardiovascular system throughout the years. Similarly, be careful not to be overly competitive when playing racquet sports.

B. the Symptoms and Signs of Stress

Sweatiness, especially on the forehead and skull, and under the armpits and on the palms owing to the presence of excess adrenaline.

Heart races and may easily pound.

Achiness in the head and neck, especially in the temples or eyes.

A feeling of turmoil or tightness in the chest or stomach as if there were butterflies in your stomach or there is a feeling of anguish, terror, fright, restlessness, agitation or tremulousness; feeling shaky, jittery, or weak all over.

Slurred speech with feelings of being unable to scream or talk for a few seconds.

Hostile, violent, full of rage and anger, and ready to fight back.

Difficulty sleeping with frequency of urination, indigestion, or sometimes diarrhea.

C. How to Handle Stress

Stress is a part of living and cannot be completely avoided. when you understand how traumatic stress can be to your heart and arteries, you may be motivated to develop techniques to deal with stress. Stress management is a complex subject, beyond the scope of this book. some of the ways that are indicated to cope with stress include mental diversion, techniques to develop a healthy self-concept, time management, progressive deep relaxation techniques, meditation, biofeedback, and exercise.

Stress is as important as the major ‘‘risk factors’’ (cholesterol, hypertension, diabetes, dyslipidemia, cigarette smoking), but it is difficult to prove this hypothesis scientifically. Stress, high blood cholesterol, hypertension, smoking, and blood-clotting factors work in concert in the genetically susceptible individual to produce atherosclerosis and, finally, a fatal or nonfatal heart attack. a stressor causes the sympathetic nervous system and adrenal glands to secrete stress hormones, which increase the work of the heart and cause platelet clumping that can sometimes cause a blood clot in the coronary artery. this chapter has outlined how excess adrenaline and noradrenaline alter the electrical stability of the heart, predisposing it to a high risk of a curious quivering (ventricular fibrillation) during which it fails to contract and sudden death may occur.

Humans are fortunate that the working of the body is such that the reaction caused by one chemical is often counterbalanced by other chemicals that are produced in the body. Nature does not always win, but it can, with a little help from you. it is important to develop strategies that may enable you to deal with various stressful

situations. Thus you will be able to handle stress and subdue the brain-adrenaline-heart-artery reaction described above.

II. TYPE a BEHAVIOR

Type a individuals have an impatient, time-conscious, achievement-striving personality, and they often seek out a hectic environment that provokes undue stress. Leisure brings a feeling of guilt, because their lives are an everlasting struggle against time toward achievement and recognition. the Type a individual takes on a project, including simple reading, with a certain violence. Speech is often harsh, explosive, or aggressive. when stressed, Type a individuals have been shown to release more adrenaline and noradrenaline and to have a greater rise in blood pressure than Type Bs. Type B people are easygoing, able to relax, and rarely carry work home or set deadlines. Most of us are mixtures of Type a and B. it is difficult for a Type a person to change, but with expert assistance, modification of lifestyle is possible.

Friedman and Rosenman have defined and established the concept of the Type a behavior pattern. They emphasized that if you have Type a behavior, you have an increased risk of coronary heart disease. Several studies have confirmed that a relationship exists between Type a behavior and risk of coronary heart disease. this occurs in both men and women independent of high blood cholesterol, hypertension, and smoking. the National Heart Lung Blood Institute has accepted the evidence regarding Type a behavior and increased risk of coronary heart disease.

The question of Type a behavior and increased risk of coronary heart disease remains controversial, however. the large Multiple Risk Factor Intervention Study and a small British study did not show any relationship between Type a behavior and coronary heart disease. a study reported in the new England Journal of Medicine found no relationship between Type a behavior and mortality from coronary heart disease in patients who had had a heart attack and were followed for three years. Commencing two weeks after their heart attack, 510 patients were followed. At the end of three years, death rate was not related to behavior, whether Type a or Type B. the mean Type a score did not differ significantly from the score of those who survived. the conclusion is: ‘‘Thus, we found no relation between type a behavior and the long-term outcome of acute myocardial infarction.

Alzheimer?s Disease

Along with the development of modern technologies, going to the moon and other exciting developments humans face the threat of diseases that affect the process of life and can be lethal in some cases. One of the illnesses that have a great affect on people’s behavior is Alzheimer’s disease (AD). Alzheimer’s disease is the degenerative disease of the brain among old people from which there is no recovery. Slowly the disease attacks the brain cells in all parts of the brain and some surrounding structures, so the an ill person loses the previous abilities to govern emotions, understand mistakes, coordinate his movements and finally a person loses all of his memory and ability to mentally function (B. Heights 2002).

AD is named after German doctor Alois Alzheimer. Dr. Alzheimer noticed changes in the brain tissue of a woman that died of an unusual mental illness. He found abnormal clumps (now called amyloid plaques) and tangled bundles of fibers (now called neurofibrillary tangles). Today, these plaques and tangles in the brain are considered hallmarks of AD. many scientists have found other brain changes in people with AD. There is a loss of nerve cells in areas of the brain that are vital to memory and other mental abilities. There also are lower levels of chemicals in the brain that carry complex messages back and forth between nerve cells. AD may disrupt normal thinking and memory by blocking these messages between nerve cells (H. Simon).

Scientists are finding specific biologic factors (Peter, Konrad, and Ballenger 2000) involved with the AD. Different environmental and genetic aspects take part in causing AD. However, the actual cause of the disease is still unknown. the greatest known risk factors for late-onset Alzheimer’s are increasing age and a family history of AD. Researches all over the world are trying to find other factors that can cause AD.

AD is nowadays the fourth leading cause of death among the adults. Nearly four million Americans have it. the number doubles every five years in people over sixty five years old. by the age of eighty five almost half of Americans have AD. some studies show that women have much higher risk of being affected by the AD than men (most of these studies were conducted on European and Asian populations, the U.S. studies, however, found no major differences). If there is a gender difference, then it is because of estrogen which is the main female’s hormone that is responsible for protecting against memory losses and normal mental functioning as compared to normal age. When a female gets older, the drop of estrogen level takes place after menopause and that could explain the higher risk of AD for older women than for men. From the other side, some of testosterone, male hormone, converts into estrogen and that could protect men. People that have a family history of the disease are above the average risk level for AD. Researchers have found that ApoE4 gene could be responsible for late and early onset cases. some studies discovered that African Americans and Hispanics are at higher risk than Caucasian Americans, AD happens less often in Native Americans Crees and Cherokees and in Asians than in regular American population. Genes may have dissimilar effects in different populations (Tanzi and Ann B. 2000).

High blood pressure and high cholesterol levels can be in fact even more risky than ApoE4. At a very high risk are also people that inherit the Down syndrome. some other risk factors are: 1) lower education and economic groups, 2) small head size, 3) Depression, 4) head injury.

A very dangerous thing about AD is that brain is being damaged for years before even the symptoms appear. the early symptoms that appear might be so mild that people could hardly notice them. the first one could be forgetfulness. People with AD may have troubles with recalling names of people that they know or remember latest events or solve simple math problems. as the disease progresses people may face

• Unreasonable weight losses

• Changes in sexuality

• Difficulties in walking

• Depression, apathy, irritability

half of all patients that have AD face the psychotic problems that can include hallucinations, visions. It is a complex form of the disease that is probably based in the genetic level. many other medical conditions have similar to Alzheimer’s symptoms. It is crucially important to identify the right disease to succeed in future treatments of it. However, we have not yet developed a test that would diagnose AD with the hundred percent guarantee. So, right now diagnosis involves ruling out other disorders the following questions about the state of a patient:

• Do psychologist tests indicate dementia?

• Does the patient have problems with using language, walking, perception?

• Has memory gotten greatly worse?

• Is the patient over 40?

• Does his/her behavior changes daily?

• Does the patient have a family history of AD?

• Are there other symptoms like depression, weight loss, hallucinations?

Other steps that are involved in making a decision involve laboratory tests (EEG and tests to rule out other diseases) and psychological testing to determine the presence of dementia.

There is no guarantee that some life styles will prevent AD, however, studies show that particular life styles can play very important role in preventing AD. It is crucial to prevent heart diseases. Calcium – Channel Blocker and other Anti – Hypertensive Agents can be used to protect the heart and consequently the brain. Statins which are the common drugs to lower the cholesterol level can also be used to lower the risk for AD. Another method that is used to prevent AD is the Hormone Replacement Therapy. because of the difference in AD rates among different populations, researches are looking at dietary factors as a protection. in China and Nigeria where fat consumption is much lower than in the U.S. the risk for AD at the age of sixty five is only 1% compared to 5% in the U.S. Studies in Netherlands reported the relationship between dementia and cholesterol levels. Eating a lot of dark colored fruits and vegetables may slow the brain degradation. Blueberries are found to be the most helpful. in any case dark colored fruits and vegetables are good for health. other studies showed that soy has estrogen which is thought to protect the memory. some reported that small consumption of alcohol can be effective in stopping the brain aging. not everybody agrees though. Caffeine has a good effect on women in terms of mental functioning. much research on AD has showed that oxidation may have an impact in the disease process. Vitamin E may protect from mental decline. other health behaviors like aerobic exercises or jogging are important in stopping the mental decline. the more person exercise the better. Another aspects that play role in the prevention of mental decline is lifelong learning and stress reduction.

Unfortunately, today we can only try to prevent AD and have no cures. However, there are drugs under investigation that are aimed to slow the progression of the AD. the bad thing is that improvements from some of these drugs can so little that a patient or his/her family would not even notice. the good thing is that even these drugs will help to postpone the necessity of taking a patient to a nursing home (Alzheimer’s Association). the only agents that are approved called selective Acetylcholinesterase inhibitors. they are designed to protect the cholinergic system which is responsible for memory and learning and is destroyed in AD. We have the following:

• Donepezil. Donepezil (Aricept) is taken once a day and has only modest benefits but it helps to slow loss of function and reduce caregiver burden. It works equally in patients with or without ApoE4. It may even have some advantage for patients with moderate to severe Alzheimer’s disease.

• Rivastigmine. Rivastigmine (Exelon) targets two enzymes (the major one, acetylcholinesterase, and butyrylcholinesterase). It is taken twice a day. this agent may be particularly beneficial for patients with rapidly progressing disease. this drug has slowed or slightly improved disease status even in patients with advanced disease. (Rivastigmine may cause significantly more side effects than donepezil, including nausea, vomiting, and headache.) as with all anticholinergics, the drug is not a cure.

• Galantamine (Reminyl). Galantamine not only protects the cholinergic system but also acts on nicotine receptors, which are also depleted during Alzheimer’s Studies report that it improves daily living, behavior, and mental functioning, including in patients with mild to advanced?moderate Alzheimer’s disease and those with a mix of Alzheimer’s disease and vascular dementia. some studies have suggested that the effects of galantamine may persist for a year or longer and even strengthen over time.

• Tacrine. Tacrine (Cognex) was the first cholinergic protective drug. It needs to be taken four times a day, has only modest benefits, and has no benefits for patients who carry the ApoE4 gene. in high doses, it can also injure the liver. in general, newer cholinergic protective drugs that do not pose as great a risk for the liver are now used for Alzheimer’s (Castleman, Gallagher-Thompson, and Naythons 2000).

Half of the patients that have mild to moderate disease show sight improvement. Latest studies, however, show little difference in effectiveness among them. all these drugs have gastrointestinal side effects, including nausea. Anyway, these drugs still have some effect. some researchers found that some patient could have no reactions to one particular drug, in this case the drug should be switched and there is actually a chance that it will work. There are also some alternative treatments that are being studied right now. One of them is Gingko Biloba. It is a common herb that increases blood flow to the brain. its extract Egb 761 may slightly improve the memory of patients that have mild to moderate AD. Gingko Biloba has only minimal side effects. Turmeric also has properties that may protect from AD. Turmeric is a spice that has curcumin as one of its components which is thought to protect from AD. Studies have also found that melatonin, the natural hormone that has to do with sleep regulation, could break down beta amyloid, and it is able to pass through the blood – brain barrier. Studies reported that melatonin improves the sleep, and in some cases even slows the mental regression (H. Simon).

A number of other medical treatments are being investigated and show promise in early or late trials. Researches are focusing on agents that can prevent the build-up of beta amyloid, its toxic effects on nerve cells, or other mechanisms of the disease process. Among them are the following:

• N?methyl?D?aspartate (NMDA) blockers. NMDA blockers, such as memantine (Ebixa), bind to glutamate, an amino acid that excites nerves and, in excess, is a powerful nerve?cell killer. Memantine has shown some to be somewhat effective in improving symptoms and is being considered for approval in Europe and the US.

• Growth factors that stimulate nerve activity in the brain. Cerebrolysin (Cere) is an example of such drugs and is showing promise in clinical trials in improving mental function and other symptoms, with sustained effects even after the drug has been stopped. Leteprinim potassium (Neotrofin) activates genes that produce nerve?growth factor in the brain. Early human trials are suggesting that it may have positive effects on memory and behavior. Insulin and insulin growth factors may prevent beta amyloid accumulation.

• Antioxidants. Indole?3?propionic acid, or IPA (Oxigon), is a natural agent that may interfere with enzymes that contribute to the Alzheimer’s disease process.

• Huperzine alpha, another acetylcholinesterase inhibitor, improved mental function, behavior, and mood in Alzheimer’s disease patients in one Chinese study. other research also suggests some benefits.

• Piracetam is a nerve protective agent called a nootropic. It has undergone a number of small studies, with few significant results. More research is needed to determine any benefits.

• Researchers are investigating immunotherapies that include vaccines, which use molecules in beta amyloid as targets for the body’s immune system, and antibodies that block proteins called CD40?CD40L, which are involved in amyloid deposition.

• Tetracyclines. Antibiotics known as tetracyclines, such as tetracycline itself, doxycycline, and minocycline, have anti?inflammatory properties that are now being investigated in a number of chronic inflammatory conditions (such as periodontal disease). they also may have activity against beta amyloid in the brain (H. Simon).

The worst thing about Alzheimer’s disease is that it is not fully investigated yet. None of the doctors can surely diagnose it. And what is even worse none can cure it. the worst thing is that AD lethal in all case. using all the treatments that have been or are still being studied can only postpone the need for the nursing home (Terry, Katzman, Bick, Sisodia 1999).

The issue of Alzheimer’s disease is crucially important to me and should be to everyone. mainly, because nobody is insured from getting AD and there is no certain way to escape it. Our modern medicine has been developing through ages and now it cures many dangerous diseases; however, it is simply helpless against the Alzheimer’s. If scholars completely investigate AD it will help to understand the brain and its impact on people’s behavior. using that knowledge it would be possible to impact the brain and its functions. unfortunately, all the studies that were conducted about AD and were presented above can not state something about AD with a hundred percent certainty. all the medications that are listed above do not stop AD; they can even hardly slow it. It is very unpleasing fact that mankind has greatly developed ways to make the brain progress but have not yet found any way to stop the regression of the brain.