Genetic factors are known to play a role in some cases of Alzheimer's disease (AD). A gene, called the amyloid beta precursor protein (APP) gene, has been linked to the occurrence of AD in Down's syndrome patients who survive beyond 40 years. Some families with a history of early-onset AD also have a mutation on the APP gene. Another gene, the Apo E gene, also has been implicated in the disease. Apo E is a protein found with beta amyloid (a protein found in the brains of AD patients) in neuritic (inflamed nerve) plaques. Together, these genetic mutations account for less than 10% of all AD cases.
Plaques and tangles: The causes of Alzheimer's disease (AD) are poorly understood, but its effect on brain tissue has been demonstrated clearly. AD damages and kills brain cells. A healthy brain has billions of nerve cells called neurons. Neurons generate electrical and chemical signals that are relayed from neuron to neuron to help an individual think, remember, and feel (physically and emotionally). Brain chemicals called neurotransmitters help these signals flow seamlessly between neurons. Initially in people with AD, neurons in certain locations of the brain begin to die. When they die, lower levels of neurotransmitters are produced, creating signaling problems in the brain. One neurotransmitter, known as acetylcholine, has been found to be deficient in the brains of those with AD. Medication treatment is based around increasing the amount of acetylcholine in the brain.
Plaques and tangles in brain tissue are considered hallmarks of Alzheimer's disease. Studies of plaques and tangles from the brains of people who have died of AD suggest several possible roles these structures might play in the disease.
Plaques are made up of beta-amyloid, a normally harmless protein. Although the ultimate cause of neuron death in AD is not known, mounting evidence suggests that a form of beta-amyloid protein may be the cause. The plaque is responsible for memory deterioration in individuals with AD.
The internal support structure for brain neurons depends on the normal functioning of a protein called tau. In people with AD, threads of tau protein undergo alterations that cause them to become twisted or tangled. Many researchers believe that this may seriously damage neurons, causing them to die.
Researchers have observed inflammation in the brains of some people with AD. Inflammation is the body's response to injury or infection and a natural part of the healing process. Even as beta-amyloid plaques develop in the spaces between neurons, immune cells are at work getting rid of dead cells and other waste products in the brain. Although research has found that the inflammation occurs before plaques have fully formed, it is not known how this development relates to the disease process. There is also debate about whether inflammation has a damaging effect on neurons or whether it is beneficial in clearing away plaques.
There's no one test to diagnose Alzheimer's disease (AD). Typically, doctors start the diagnostic process by ruling out other diseases and conditions that may also cause memory loss. Small, undetected strokes, which are a lack of oxygen to the brain causing neurological damage, can cause dementia. Individuals with Parkinson's disease, a degenerative nerve disorder, also may develop dementia. Depression can also cause lapses in memory. In addition, many older adults are on multiple medications that may decrease their ability to think clearly.
Medical history: Questions regarding general health and current medications will be asked. Past medical problems, including diseases and surgeries, will be discussed. Family members will usually be involved in the medical history process.
Blood tests: Blood tests to determine basic health will be used. A complete blood count (CBC) will determine thyroid problems, electrolyte (such as sodium and potassium) balances, vitamin deficiencies, and immune health.
Mental status evaluation: A Mental Status Evaluation (MSE) screens memory, problem-solving abilities, attention spans, counting skills, and language skills. Questions such as "what day is it today?" or "who is the president of the United States?" may be asked. Recall tests are another example. Doctors may list familiar objects and then ask a person to repeat them immediately and again five minutes later. The Clock Drawing Test, the Mini-Mental State Examination (MMSE), and the Functional Assessment Staging (FAST) are commonly used mental status evaluation tools for determining if AD is present. On the tests, the final score helps confirm a diagnosis of AD.
Sometimes doctors will more extensively assess memory, problem-solving abilities, attention spans, counting skills, and language. This is especially helpful in trying to detect AD and other dementias at an early stage. Doctors use formal psychological tests to determine if an individual's mental abilities are as expected for his or her age and education. The patterns of any mental deficits observed during neuropsychological testing can help doctors sort out possible causes of dementia.
Brain scans: Doctors may want to take a picture of the brain using a brain scan. Several types of brain scans are available including computerized tomography (CT) scan, magnetic resonance imaging (MRI) scan, and positron emission tomography (PET) scan. Doctors can pinpoint visible abnormalities in the brain using these imaging techniques. A CT scan uses x-rays to take many pictures of the brain and then combines the pictures by computer that provides a detailed picture. A CT scan can often show changes in brain structure. MRI's for AD diagnosis display a cross-section of the brain using radio waves and strong magnets instead of radiation. A contrast dye may be injected, although it is used less often with MRI's. PET scans involve the injection of radioactivity into the blood that goes to the brain. Images can then be analyzed for changes in function and structure of the brain. They may take longer than CT scans and the patient is placed inside a confining tube. CT, MRI, and PET are performed at a clinic or hospital. Some individuals will be sedated with mild sedatives (such as alprazolam or Xanax® or midazolam or Versed®). These medications may cause drowsiness and it is not recommended that the individuals drive. The individual should bring a friend or family member with them to the clinic or hospital.
Genetic testing: Due to the discovery of genes that are associated with developing AD, genetic testing may be used in the future as a routine diagnostic tool for determining the chances of developing AD. Genetic testing is not approved by the U.S. Food and Drug Administration (FDA) for use in AD diagnosis.
signs and symptoms
Because early symptoms of Alzheimer's disease (AD) progress slowly, diagnosis is difficult and often delayed. The disease's course varies from person to person. Eight years is the average length of time from diagnosis of Alzheimer's to death. Survival begins to decline three years after diagnosis, but some people live more than a decade with the disease.
Stages of AD: In individuals with AD, changes in the brain may begin 10-20 years before any visible signs or symptoms appear. Some regions of the brain may begin to shrink (found during brain imaging such as positron emission tomography or PET), resulting in memory loss and the first visible sign of AD. Over time, AD progresses through three main stages including mild (early), moderate, and severe.
Individuals with mild symptoms of AD often seem healthy, but mental deterioration, such as memory impairment and confusion, are occurring. Symptoms and early signs of Alzheimer's disease may include: difficulty learning and remembering new information, difficulty with daily tasks (such as managing finances, planning meals, and taking medication on schedule), and depression symptoms (sadness, decreased interest in usual activities, loss of energy). The individual is usually still able to do most activities such as driving a car, but may get lost going to familiar places.
People with early and mild symptoms of AD may exhibit mood swings. They may express distrust in others, show increased stubbornness, and withdraw socially. This may be a response to the frustration they feel as they notice uncontrollable changes in their memory. Restlessness also is a common sign. As the disease progresses, people with Alzheimer's may become anxious or aggressive and behave inappropriately.
Moderate symptoms: In individuals with moderate symptoms of AD, the damaging processes occurring in the brain worsen and spread to other areas that control language, reasoning, sensory processing, and thought. In this stage, symptoms and signs of AD become more severe and behavioral problems may become more obvious. Signs and symptoms of moderate Alzheimer's disease may include forgetting old facts, continually repeating stories, and/or asking the same questions over and over. The individual may make up stories to fill memory gaps. They have difficulty performing tasks such as keeping a checkbook, shopping for groceries, or following written notes. The individual may not shower or go to the toilet as they did previously, and help with these tasks is needed. They become agitated and restless easily. Repetitive movements, such as rocking to and fro or rubbing the hands, are seen. The individual may wander off and needs to be watched closely. Paranoia, delusions, and hallucinations may occur. Deficiencies in intellect and reasoning, along with a lack of concern for appearance, hygiene, and sleep, become more noticeable.
Severe symptoms: In the advanced stage of AD, damage to the brain's nerve cells is widespread. At this point, full-time care is typically required. The patient is generally bed-ridden. For friends, family, and Alzheimer's caregivers, this can be the most difficult stage. Individuals with severe Alzheimer's disease may have difficulty walking and they often suffer complications from other illnesses such as pneumonia. Signs of severe Alzheimer's disease may include groaning, screaming, mumbling, or speaking gibberish. They refuse to eat and may inappropriately cry out. Individuals with severe or advanced symptoms fail to recognize the faces of family members or caregivers. Apraxia (inability to perform physical tasks such as dressing, eating) and aphasia (loss of ability in comprehension of spoken or written language) are seen. They have great difficulty with all essential activities of daily life.
Mental Illness: Depression is common in patients with Alzheimer's disease (AD), especially during the earlier stages when they may be aware of losing mental functions.
Falls and their complications: Individuals with AD may become disoriented, increasing their risk of falls. Falls can lead to bone fractures that require hospitalization, medications, and surgery. Falls may also lead to an increase in the severity of AD symptoms, such as confusion and agitation. In addition, falls are a common cause of serious head injuries, such as brain hemorrhage (bleeding in the brain). Long-term immobilization after surgery and hospitalization may also increase the risk of a pulmonary embolism (blood clot in the lungs), which can be life-threatening.
Infections: In advanced Alzheimer's disease, people may lose all ability to care for themselves. This can make them more prone to additional health problems such as pneumonia (a bacterial infection of the lungs and respiratory system). They may have difficulty swallowing food and liquids, which may cause individuals with AD to inhale some of what they eat and drink into their airways and lungs, which may then lead to pneumonia.
Urinary incontinence: Urinary incontinence, or the loss of bladder control causing urine leakage, may require the placement of a urinary catheter, which increases the risk of urinary tract infections (UTIs). UTIs can lead to more serious, life-threatening infections.
Age: The risk for Alzheimer's disease (AD) increases with each decade of adult life. AD usually affects people older than 65 but rarely, it may affect those younger than 40. Less than five percent of people between 65-74 years old have AD. For people 85 and older, that number jumps to nearly 50%.
Heredity: The risk of developing AD appears to be slightly higher if a first-degree relative (a parent, sister, or brother) has the disease. Although the genetic link of AD among families remains largely unexplained, researchers have identified a few genetic mutations that greatly increase risk in some families. A clear inherited pattern of AD exists in less than 10% of cases. In addition, one form of the apolipoprotein E (APOE) gene increases the chances of developing late-onset AD. Nearly all individuals with Down's syndrome who live into their 40s develop the disease. Down syndrome (DS) is a condition in which extra genetic material causes delays in the way a child develops and often leads to mental retardation. It affects one in every 800 babies born. Three genetic mutations in DNA are known to cause early-onset Alzheimer's.
Sex: It is thought that gender plays a role because several clinical studies suggest that women are afflicted with Alzheimer's disease more often than men. This was explained by the life span of women being usually longer than men. However, the evidence is inconsistent and some studies report that the disease is more common in men. Therefore, more research is needed to obtain conclusive evidence regarding prevalence in gender.
Lifestyle: The same factors that put an individual at risk of heart disease, including hypertension (high blood pressure) and hypercholesterolemia (high cholesterol), may also increase the likelihood that the person will develop AD. Poorly controlled diabetes is another risk factor. Exercise and diet are very important to prevent and control AD. Some clinical studies have suggested that remaining mentally active throughout life, especially in the later years, reduces the risk of AD. Mental activity can be doing crossword puzzles daily, reading the newspaper or books, and increasing social activities.
Education levels: Clinical studies have found an association between less education and the risk of developing AD. Some researchers theorize that the more an individual uses his/her brain, the more synapses are created, which provide a greater reserve as an individual ages. It remains unclear, however, whether less education and less mental activity create a risk of AD or if it is simply harder to detect AD in individuals who exercise their minds frequently or who have more education. Reading, working, puzzles, and social activities help exercise the mind.
Toxicity: Another theory is that overexposure to metals (such as lead, mercury, and aluminum) or chemicals may cause AD. For a time, aluminum was thought to increase the likelihood of developing AD. This was due to the findings that more individuals with AD have deposits of aluminum in their brains. After many years of studies, however, no true link to developing AD has been found with aluminum exposure. A study found that workers exposed to aluminum experienced neurotoxicity (nerve damage) and symptoms of early AD, such as decreased cognitive performance. More studies need to be performed to link heavy metals to AD.
Head injury: The observation that some ex-boxers eventually develop dementia suggests that serious traumatic injury to the head (for example, a concussion with a prolonged loss of consciousness) may be a risk factor for AD. Findings are mixed and more research is needed.
Hormone replacement therapy: The exact role hormone replacement therapy (HRT) may play in the development of dementia and AD is not yet clear. Early evidence seemed to report that estrogen supplements given after menopause could reduce the risk of dementia and AD. But results from the large-scale Women's Health Initiative Memory Study indicated an increased risk of AD for women taking estrogen after age 65. The verdict is not yet in on whether estrogen affects the risk of dementia and AD if given at an earlier age. More research is needed.