Alzheimer’s disease (AD) is a progressive, neurodegenerative disease that accounts for 50% to 75% of all dementias affecting older adults. AD affects 5% to 10% of all adults older than 65 years, and this proportion doubles every 5 years over 65; consequently, it is a major health concern in the United States. About 4.5 million people had the disease in 2004, and this number will rise to about 11 million by 2025. Considering that most individuals with AD spend at least some time in a full-care facility, health care costs associated with the disease are high. Costs associated with AD in 2004 approached $1 billion per year, and these will continue to increase as the population ages. The high incidence of institutionalization stems from the cognitive effects of the disease. People with AD gradually become unable to accomplish everyday tasks like driving and cooking; their abilities to communicate and manage their own grooming and self-care deteriorate, and eventually control of bodily functions and motor abilities is lost. However, the most devastating effect, particularly for family members, is the gradual deterioration of personality: Affected individuals lose interest in hobbies and outside events, fail to recognize family members, and eventually cease to interact with the world around. Thus, the disease is devastating on both societal economic and personal-familial levels. Intense research continues to investigate etiological factors, cognitive sequelae, and treatments for this debilitating illness.
Biological And Genetic Characteristics
The characteristic histological markers of ADare intercellular neuritic plaques and intracellular neurofibrillary tangles. Plaques occur in the spaces between neurons and comprise a beta-amyloid (βamyloid) protein core surrounded by a cluster of dead and dying neurons. Neurofibrillary tangles consist of the tau protein fibers that normally organize and give shape to a cell but that have become deformed, possibly as a result of interaction with β-amyloid. The tau protein aggregates into intracellular tangles that block the normal flow of nutrients and information within the neuron. Consequently, the number of synapses the cell can maintain with other cells diminishes, and eventually the cell dies.
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Amyloid proteins transport cholesterol throughout the body and brain so that it can be used for cellular repair. β-Amyloid is one of three common variants of the amyloid protein, and unlike other variants, none of the enzymes normally produced by the body can break it down. Moreover, the β-amyloid protein is particularly sticky and has been associated with the deposition of fatty cholesterol deposits in blood vessels as well as with neuritic plaques in AD. Consequently, the individual who has this version of the amyloid protein is at risk for cardiovascular disease in addition to AD. β-Amyloid protein is encoded by a particular gene on chromosome 19, known as the apolipoprotein ε4 (ApoE4) gene. This gene variant cuts the amyloid precursor protein in a different place than normal, yielding the insoluble β-amyloid. Like all genes, individuals have two copies of the ApoE gene. People carrying one copy of ApoE4 (about 25% of the population) have a higher risk for AD than individuals with other variants of the ApoE gene; individuals who carry two copies of the ApoE4 gene (about 2% of the population) have a much higher risk for developing AD at a younger age than those with only one copy of the gene. In fact, the ApoE4 gene variant accounts for about 50% of all cases of late-onset AD, that is, AD diagnosed after age 60. Furthermore, compared with noncarriers, carriers of the ApoE4 gene show metabolic differences in their brain in the same areas that are affected by AD as early as age 30; however, cognitive differences are minimal or absent between noncarriers and carriers of the ApoE4 gene from age 30 to 55. Early-onset AD refers to the 1% of AD cases that are diagnosed in people in their 40s and 50s, caused by mutations to genes other than ApoE. In addition to genetics, other risk factors for AD include increasing age, family history of AD, previous head trauma or stroke, and lower education and verbal ability.
AD preferentially targets brain centers that control higher cognitive abilities. The hippocampal region in the medial temporal lobe is affected first, hampering the ability to encode new memories, followed by the posterior cingulate, which is instrumental in making and evaluating decisions. Subsequently, the multimodal association cortices in the temporal and parietal lobes show signs of the disease, leading to difficulties with language use and spatial-temporal orientation. Later, the prefrontal cortex shows signs of the disease, which is reflected in attentional and behavioral deficits, as discussed subsequently.
Physicians suspect AD might be present when individuals show a decline in memory ability and at least one other cognitive domain (e.g., language, orientation in time and space, or executive functions) that affects their daily occupational and social activities. Furthermore, this decline must have a gradual onset and must continue over time. To make a clinical diagnosis of AD, the doctor must exclude a number of other possible causes for this decline. Physicians use in-depth interviews, blood tests, and brain imaging (usually computed tomography scans or magnetic resonance imaging) to rule out depression, drug interactions, endocrine disorders, nutritional deficiencies, head trauma, brain tumor, and stroke as causes of decline before making a diagnosis of probable AD. It is still not possible to make a positive diagnosis of AD until autopsy; however, imaging techniques that highlight amyloid deposition in the brain have been developed recently that may allow in vivo diagnosis of AD in the near future.
AD has profound effects on cognition, speech, and overall behavior that vary individually, depending on the sequence in which different parts of the brain are affected. By the time individuals are diagnosed with AD, usually at the very mild or mild stage of the disease, damage to hippocampus and posterior cingulate is typically already relatively severe, leading to deficits in learning new information, short-term memory, autobiographical memory, and judgment. Consequently, people with AD often repeat questions and stories and make poor decisions because they cannot assimilate new information. Additionally, these individuals often have word-finding problems and difficulty expressing themselves, and their attentional and spatial impairments make driving hazardous. Even at this mild stage of the disease, individuals have severe difficulty with organizing, planning, problem solving, and abstract reasoning. Typically, individuals are aware of their deficits and are often depressed and irritable. As the disease progresses, this awareness diminishes while memory and language problems increase.
At the moderate stage of the disease, typical, daily activities become increasingly difficult: the individual cannot prepare meals, use tools, or even take telephone messages. Although automatized tasks like self-grooming may be preserved, concerns about personal hygiene and appearance often suffer. Speech becomes vague and usually includes an overabundance of pronouns replacing more specific nouns, whereas the ability to comprehend complex sentences and discourse deteriorates. At this stage of the disease, many people with AD feel a profound restlessness and may begin to wander away from home. Because they become easily lost and often cannot remember their address or phone number, wandering can be a serious problem. Sleep difficulties, hallucinations, and personality changes are also common at this stage of the disease.
At the severe stage of AD, individuals slowly lose interest in their surroundings. Their ability to communicate relevantly declines and eventually disappears, as they lapse into mutism. They can no longer groom themselves and become incontinent. Additionally, they may not recognize common items, including food, and may have difficulty swallowing, which can lead to resistance to eating and drinking and subsequent malnutrition. They become agitated over changes in routine, and the loss of personality is profound. Eventually, they become bedridden and unresponsive; death, however, is usually due to infection or other complications.
Current treatments for AD are based on the fact that AD affects the brain’s ability to produce many of the neurotransmitters crucial for memory and cognition. The primary drugs used in early AD, tacrine and donepezil, are acetylcholinesterase inhibitors, which prevent the breakdown of acetylcholine, a neurotransmitter necessary for memory function. In about 50% of individuals with early AD, these drugs minimize or slow the deterioration of cognitive abilities and help control behavioral problems, such as depression, agitation, and insomnia. Research to develop a vaccine that would prevent the accumulation of β-amyloid in the brain is in progress, but to date has been unsuccessful.
Maintaining communication with the individual with AD can help mitigate the burden the disease places on caregivers. Certain strategies can facilitate this communication, such as minimizing environmental distractions, limiting the use of pronouns and complex grammar, maintaining eye contact, and repeating or paraphrasing important information. Caregivers should also be encouraged to take advantage of home health care and adult day care services where available, as well as support groups, because the constant demands of caregiving can be debilitating both physically and emotionally.
In summary, AD is a devastating disease with enormous human and economic costs that will continue to increase as the population ages. However, research continues to identify ways to treat the disease and to improve quality of life for individuals with the disease and their caregivers.
- Alzheimer’s Association, http://www.alz.org
- Alzheimer’s Disease Education and Referral Center of theNational Institute on Aging, http://www.alzheimers.org
- Kuhn & Bennett, D. A. (2003). Alzheimer’s early stages: First steps for family, friends, and caregivers (2nd ed.). Alameda, CA: Hunter House Publishers.
- Weiss, (2004). When the doctor says Alzheimer’s: Your caregiver’s guide to Alzheimer’s and dementia. Bloomington, IN: AuthorHouse.