Alzheimer's disease Diagnosis

  • Diagnosis

    Alzheimer's disease is a slowly progressive, irreversible brain disease that results in memory loss, impaired thinking ability, and ultimately changes in behavior or personality. The symptoms of Alzheimer's disease progress over time from mild forgetfulness to severely impaired mental function. These symptoms result from the death of brain cells and the lost connections between them. The course of the disease, including the range of symptoms and the speed at which mental function declines, varies widely from individual to individual. People with Alzheimer's disease live an average of eight to ten years after diagnosis, but some may live for twenty years or more.

    Alzheimer's disease is not a normal consequence of growing older. Alzheimer's disease is more than simple forgetfulness. During normal aging, nerve cells in the brain are not lost in large numbers. However, in Alzheimer's disease, large numbers of nerve cells in the brain stop functioning, lose their connections with other nerve cells, and die.

    Alzheimer's disease is the most common form of dementia, and the ninth leading cause of death in adults over 65 years of age. Dementia is the term used to describe a persistent, usually irreversible decline in mental abilities. Dementia can be caused by brain diseases such as Alzheimer's or Huntington's disease, or by conditions that affect the brain indirectly, such as clogged blood vessels leading to stroke, certain vitamin deficiencies (such as B12 deficiency), thyroid disorders, pituitary disease, HIV infection, or syphilis.

    Alzheimer's disease is the most common cause of dementia among people over the age of 65. Approximately four million Americans live with the disease, and this number is expected to grow rapidly as the U.S. population ages.

    The causes of Alzheimer's disease are not well understood, but the condition is most likely due to a destructive accumulation of a protein (called beta amyloid) outside brain cells. Genetic and environmental factors both contribute to the accumulation of beta amyloid in the brain Figure 01. These deposits or plaques are a hallmark feature of Alzheimer's disease. Plaques are a dense composite of beta amyloid protein and other cellular materials that accumulate around the nerve cells in the brain. It is not fully understood exactly how amyloid plaques destroy nerve cells.

    A second abnormal structure, the neurofibrillary tangle, also has a role in Alzheimer's disease, although it is thought to play a secondary role. Neurofibrillary tangles are twisted fibers that build up inside brain cells. Tangles are formed from a type of protein (called tau) that normally constitutes part of the internal support structure of the cell. These intracellular tangles disrupt communication between brain cells and eventually destroy them.

    Click to enlarge: Beta amyloid plaques and neurofibrillary tangles

    Figure 01. Beta amyloid plaques and neurofibrillary tangles

    Although the extent and rate of mental impairment varies among people with Alzheimer's, the disease generally progresses through several stages from mild symptoms to eventual death Table 01.

    The earliest symptoms of Alzheimer's disease include forgetfulness and mild depression. The early symptoms of Alzheimer's are mild, and often begin insidiously. They typically include slight forgetfulness, mild depression, and apathy characterized by loss of interest in normal pursuits. As the disease progresses, memory loss worsens, and other symptoms of impaired mental function begin to interfere with daily activities.

    During the mild stage of the disease, problems with abstract thinking, misplacing things, repeating questions, and becoming disorientated to time and place are common. Although mental impairment becomes increasingly obvious during this stage of the disease, Alzheimer's patients may be able to maintain independence. Some people with Alzheimer's are unaware of their difficulties; others have considerable insight into their loss of memory and cognition. Minor memory distortions are common during this stage. For example, patients may believe that they have turned off the stove or taken their medications when they have only thought about these activities. Difficulty paying the bills and balancing the checkbook typically begin to become evident.

    During the moderate stage of Alzheimer's, memory loss worsens, and problems with language and other cognitive skills become evident. Altered mood and behavior such as depression and irritability commonly appear during this stage. Restlessness, wandering, delusions, and hallucinations may occur. Memory distortions become more evident and extreme; patients may believe events occurred that are either combinations of real events or entirely fictitious. Patients also frequently believe that relatives long deceased are still living. They are often confused by minor changes in the environment. Language skills, including comprehension and naming objects, become deficient. Problem-solving skills deteriorate as well. Various impairments in activities of daily living, such as dressing, eating, and grooming become evident, and the individual becomes increasingly dependent on others.

    Advanced Alzheimer's is characterized by severe memory loss, failure to recognize family members, severely impaired language skills and other cognitive abilities, loss of bladder control, and complete dependence on others for basic needs. Eventually, the person with Alzheimer's becomes bedridden, mute, and unresponsive. Patients with Alzheimer's disease do not die of the disease per se, but are often unable to remember or even communicate their symptoms, such as chest or abdominal pain. Death may occur from pneumonia, malnutrition, heart disease, or systemic infection, among other causes.

    Table 1.  The Stages of Alzheimer's Disease

    Stage Symptoms/observations
    Very mild Difficult to date onset; insidious progression
    Repetitive questions or statements
    Loses objects, and cannot find them without help
    Failure to recall conversations
    Imperfect recall of newly learned information (recent events, new acquaintances)
    Previously learned material is preserved
    Mild Mild memory distortions occur
    Increasing forgetfulness
    Minor temporal and geographical disorientation (needs directions to find familiar locations)
    Judgment and problem-solving are impaired (less capable of operating appliances, operating a motor vehicle, balancing a checkbook, and increased susceptibility to solicitations and con artists)
    Language disturbances (word-finding difficulty, speech hesitancy, diminished oral and written output)
    Personality changes (apathy, irritability, and mild paranoia)
    Moderate New information is rapidly forgotten
    Frequent memory distortions (long-deceased persons discussed as if still living, confusion about relationships of living relatives)
    May become lost in familiar surroundings
    Judgment and problem-solving notably impaired (driving and other complex activities abandoned, social graces decline)
    Language skills deteriorate further (incomplete or circumlocutory sentences and poor comprehension of spoken and written language)
    Disruptive behaviors emerge in some patients (agitation, restlessness-wandering, day-night disorientation, sleep disturbances, aggressive verbal or physical behavior, suspiciousness and delusions)
    Self-care activities require supervision
    Increasing dependence on others
    Severe Memory only fragmentary (may recognize spouse and children)
    Verbal output limited to short phrases or repeated words
    Comprehension limited to the simplest spoken language
    Disruptive behaviors in some patients while resolving in others
    Personality deteriorates and the person with Alzheimer's disease may not seem like their old self
    Difficulty moving about
    Urinary and fecal incontinence
    Nearly complete dependence on caregivers for activities of daily living such as eating and dressing

    The most important risk factor for Alzheimer's disease is age. The condition typically appears after age 65, and becomes increasingly common with greater age. The disease affects an estimated 20% to 40% of people over the age of 85.

    A rare form of Alzheimer's disease has a genetic link, and runs in families. Unlike most cases, it affects people between 30 and 60 years of age. Individuals with Down syndrome have a higher risk of developing Alzheimer's disease in their 40 and 50s than the general population. Inherited cases represent a small minority of all Alzheimer's disease. Approximately half of these cases are caused by changes in one of three different genes: two genes called presenilin 1 and presenilin 2, and the APP gene, which is responsible for a protein that eventually becomes beta amlyoid. Studies are now being performed to identify the function of these genes, and to determine how changes in them cause Alzheimer's disease. In addition, as researchers learn more about this form of the disease, more genes involved in the process are likely to be identified.

    Late-onset Alzheimer's may also have a genetic trigger. Variations in a gene that encodes the protein apolipoprotein E (ApoE) have been linked to different risks of developing late-onset Alzheimer's disease. ApoE is a normal protein in the body that helps to carry cholesterol in the blood; however, it is found in excessive amounts with the amyloid plaques in the brains of people with Alzheimer's disease. The ApoE gene has four forms, and your body carries two at one time. One combination of the ApoE genes appears to increase a person's risk of developing Alzheimer's at an earlier than normal age. Another is associated with a lower risk and later age of onset if Alzheimer's does develop.

    Several other risk factors for Alzheimer's disease have been suggested, with varying degrees of supporting clinical evidence. Postmenopausal estrogen use has been associated with decreased rates of Alzheimer's disease in some studies. Head trauma, low educational level, and environmental factors such as mercury, viruses, and infectious proteins (prions) have all been suggested as risk factors. However, none has been proven in well-designed studies to play a role in the disease. Aluminum has often been brought up as a potential cause of Alzheimer's disease, but no link between exposure to aluminum (for example, from aluminum cookware) and Alzheimer's disease has ever been found.

    Alzheimer's disease is only one of several dementias that affect older adults. Your doctor will have to make an accurate diagnosis to rule out other potentially treatable illnesses that may be causing your symptoms. Other diseases that can cause Alzheimer's-like symptoms include dementia due to clogged arteries in the brain (vascular dementia), a buildup of fluid within the brain, normal-pressure hydrocephalus, and dementia associated with Huntington's disease, HIV infection, Parkinson's disease, or syphilis. In addition, certain vitamin deficiencies (e.g., B12), certain hormonal disorders (thyroid and pituitary, for example), and side effects of drugs can cause symptoms similar to those of Alzheimer's disease.

    During the initial evaluation, the doctor will complete a careful medical history. Because a patient is often already experiencing memory loss by the time he or she goes to see a doctor, the help of a spouse or other family member is usually required. The doctor will ask questions about specific memory, cognitive, or behavioral problems the patient is experiencing, and the time at which they developed. The answers to these questions not only help to diagnose and stage the problem, but also provide a baseline for comparison of subsequent disease progression. The medical history will also include a series of questions intended to rule out other potentially treatable causes of the symptoms.

    The initial evaluation will include mental status testing. Mental status testing is done by asking the patient questions, or by using standardized tests that measure various aspects of memory and cognition. The Mini Mental Status Examination, Blessed Dementia Scale, and 7-Minute Screen are some common examples. These tests, however, need to be interpreted by clinicians who can take into account factors such as education and baseline ability prior to the development of symptoms. For example, a mathematics professor should not be considered “normal” just because he can still balance his checkbook.

    Your doctor will perform a physical examination and order laboratory tests to determine whether any co-existing or alternate causes of the dementia are present. A physical examination may identify signs of vascular disease, liver or kidney disease, drug toxicity, or vitamin deficiencies. The examination may also identify co-existing conditions—such as difficulty hearing or seeing—that could exacerbate the patient's condition. Typical tests include blood counts, blood chemistry, thyroid tests, and tests to identify systemic infections. The doctor will also order computed tomography (CT) or magnetic resonance imaging (MRI) of the head to identify strokes, brain tumors, or the build-up of fluid within or around the brain.

    Alzheimer's disease is diagnosed when other potential causes of progressive memory loss and cognitive impairment have been ruled out. A definitive diagnosis of Alzheimer's disease can only be made after death, when the characteristic plaques and tangles of Alzheimer's disease are identified during an autopsy of the brain. Few people actually undergo an autopsy. For a diagnosis of probable Alzheimer's disease, the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association uses the following definition: established dementia, deficits in two or more types of thought processes (for example, memory), progressive worsening of memory and other thought processes, no disturbance in consciousness, onset between 40 and 90 years of age, and absence of other brain diseases that could account for the symptoms.

    Currently, Alzheimer's disease cannot be prevented, though scientists are researching possible methods to prevent it. Genetic testing can identify people with an increased risk of developing the disease, but without a cure or treatment that can stop the disease from progressing, such knowledge has limited value.

  • Prevention and Screening

    Currently, Alzheimer's disease cannot be prevented, though scientists are researching possible methods to prevent it. Genetic testing can identify people with an increased risk of developing the disease, but without a cure or treatment that can stop the disease from progressing, such knowledge has limited value.

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