Alzheimer's Disease

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Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive deterioration together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes. It is the most common cause of dementia.


Dementia is a brain disorder that seriously affects a person's ability to carry out daily activities. Alzheimer's disease is the most common form of dementia among older people. It involves the parts of the brain that control thought, memory, and language. Every day scientists learn more, but right now the causes of Alzheimer's disease are still unknown, and there is no cure.


The most striking early symptom is loss of short term memory (amnesia), which usually manifests as minor forgetfulness that becomes steadily more pronounced with illness progression, with relative preservation of older memories. As the disorder progresses, cognitive (intellectual) impairment extends to the domains of language (aphasia), skilled movements (apraxia), recognition (agnosia), and those functions (such as decision-making and planning) closely related to the frontal and temporal lobes of the brain as they become disconnected from the limbic system, reflecting extension of the underlying pathological process.


This pathological process consists principally of neuronal loss or atrophy, principally in the temporoparietal cortex, but also in the frontal cortex, together with an inflammatory response to the deposition of amyloid plaques and neurofibrillary tangles.


The ultimate cause of the disease is unknown. Genetic factors are known to be important, and autosomal dominant mutations in three different genes (presenilin 1, presenilin 2, and amyloid precursor protein) have been identified that account for a small number of cases of familial, early-onset AD. For late onset AD (LOAD), only one susceptibility gene has so far been identified: the epsilon 4 allele of the apolipoprotein E gene. Age of onset itself has a heritability of around 50%.


History

Alois Alzheimer
In 1901, Dr. Alois Alzheimer, a German psychiatrist, interviewed a patient named Mrs. Auguste D, age 51. He showed her several objects and later asked her what she had been shown. She could not remember. He would initially record her behavior as "amnestic writing disorder," but Mrs. Auguste D. would be the first patient to be identified with Alzheimer's disease.


Alzheimer would later work in the laboratory of the esteemed Emil Kraepelin in Munich, Germany. Kraepelin was the author of a leading textbook in psychiatry and was a strong believer that neuropathology could be linked to clinical psychiatric function. Early in April 1906, Auguste D died, and Alzheimer worked with two Italian physicians to examine her anatomy and neuropathology. On November 3, 1906, he presented Auguste D's case to the 37th Assembly of Southwest German Psychiatrists and described the neurofibrilary tangles and amyloid plaques that would be the hallmark of the disease. Kraepelin would later write about this case and others in his Textbook for Students and Doctors and index them under Alzheimer's disease. By 1910, the name of the disease was well established among the specialist community.


For most of the twentieth century, the diagnosis of Alzheimer's disease was reserved for individuals between the ages of 45–65 who developed symptoms of presenile dementia due to the histopathologic process discovered by Dr. Alzheimer (see below for description of brain tissue changes). During this time senile dementia itself (as a set of symptoms) was considered to be a more or less normal outcome of the aging process, and thought to be due to age-related brain arterial "hardening." In the 1970s and early 1980s, because the symptoms and brain pathology were identical for Alzheimer victims older and younger than age 65, the name "Alzheimer's disease" began to be used, within and outside the medical profession, equally for afflicted individuals of all ages, although in this period the term senile dementia of the Alzheimer type (SDAT) was often used to distinguish those over 65 who did not fit the classical age criterion. Eventually, the term Alzheimer's disease was adopted formally in the psychiatric and neurological nomenclature to describe individuals of all ages with the characteristic common symptom pattern, disease course, and neuropathology. The term Alzheimer disease (without the apostrophe and s) also continues to be used commonly in the literature.


Clinical features

The usual first symptom noticed is short term memory loss which progresses from seemingly simple and often fluctuating forgetfulness (with which the disease should not be confused) to a more pervasive loss of short-term memory, then of familiar and well-known skills or objects or persons. Aphasia, disorientation and disinhibition often accompany the loss of memory. Alzheimer's disease may also include behavioral changes, such as outbursts of violence or excessive passivity in people who have no previous history of such behavior. In the later stages, deterioration of musculature and mobility, leading to bedfastness, inability to feed oneself, and incontinence, will be seen if death from some external cause (e.g. heart attack or pneumonia) does not intervene. Average duration of the disease is approximately 7–10 years, although cases are known where reaching the final stage occurs within 4–5 years, or up to 15 years.


Stages and symptoms

  • Mild — At the early stage of the disease, patients have a tendency to become less energetic or spontaneous, though changes in their behaviour often goes unnoticed even by the patients' immediate family.
  • Moderate — As the disease progresses to the middle stage, the patient might still be able to perform tasks independently, but may need assistance with more complicated activities.
  • Severe — As the disease progresses from the middle to late stage, the patient will undoubtedly not be able to perform even the simplest of tasks on their own and will need constant supervision.


Diagnosis

The diagnosis is made primarily on the basis of history, clinical observation and tests of memory and intellectual functioning over a series of weeks or months, with various physical tests (blood tests and neuroimaging) being performed to rule out alternative diagnoses. No medical tests are available to diagnose Alzheimer's disease conclusively pre-mortem. Expert clinicians who specialize in memory disorders can now diagnose AD with an accuracy of 85–90%, but a definitive diagnosis of Alzheimer's disease must await microscopic examination of brain tissue, generally at autopsy. Functional neuroimaging studies such as PET and SPECT scans can provide a supporting role where dementia is clearly present, but the type of dementia is questioned. Recent studies suggest that SPECT neuroimaging approaches clinical exam in diagnostic accuracy and may outperform exam at differentiating types of dementia. However, Alzheimer's disease remains a primarily clinical diagnosis based on the presence of characteristic neurological features and the absence of alternative diagnoses, with neuroimaging providing a supporting role where dementia is clearly present, but the type of dementia is questioned.


Interviews with family members and/or caregivers are extremely important in the initial assessment, as the sufferer him/herself may tend to minimize his symptomatology or may undergo evaluation at a time when his/her symptoms are less apparent, as quotidian fluctuations ("good days and bad days") are a fairly common feature. Such interviews also provide important information on the affected individual's functional abilities, which are a key indicator of the significance of the symptoms and the stage of dementia.


Initial suspicion of dementia may be strengthened by performing the mini mental state examination, after excluding clinical depression. Psychological testing generally focuses on memory, attention, abstract thinking, the ability to name objects, visuospatial abilities, and other cognitive functions. Results of psychological tests may not readily distinguish Alzheimer's disease from other types of dementia, but can be helpful in establishing the presence of and severity of dementia. They can also be useful in distinguishing true dementia from temporary (and more treatable) cognitive impairment due to depression or psychosis, which has sometimes been termed "pseudodementia". In addition, a 2004 study by Cervilla and colleagues showed that tests of cognitive ability provide useful predictive information up to a decade before the onset of dementia.


patients should not be diagnosed from the standard norm but from an adjusted high-IQ norm that measured changes against the individual's higher ability level.


Pathology

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Biochemical characteristics

Alzheimer's disease has been identified as a protein misfolding disease due to the accumulation of abnormally folded amyloid beta protein in the brains of AD patients.[1]
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