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.
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