What causes Alzheimer's disease?
Alzheimer's disease affects brain cells, preferentially those in brain regions responsible for learning, reasoning, and memory. Autopsy of a person with Alzheimer's disease shows that these regions of the brain become clogged with two abnormal structures, called neurofibrillary tangles and senile plaques. Neurofibrillary tangles are twisted masses of protein fibers inside nerve cells, or neurons. Senile plaques are composed of parts of neurons surrounding a group of brain proteins called beta-amyloid deposits. While it is not clear exactly how these structures cause problems, some researchers now believe that their formation is in fact responsible for the mental changes of Alzheimer's disease, presumably by
interfering with the normal communication between neurons in the brain. Two drugs approved by the Food and Drug Administration (FDA) as of January 1998 both act to increase the level of chemical signaling molecules in the brain, known as neurotransmitters, to make up for this decreased communication ability.
Alzheimer's disease is a hereditary disorder in which nerve cells in the brain, called neurons, die, making it difficult for the brain to work properly. Neuron death begins insidiously, many years before the onset of memory loss or other symptoms of the disease. During this pre-symptomatic period, there are no obvious symptoms because remaining nerve cells compensate for the net loss. In fact, the brain can lose nearly four-out-of-five nerve cells and still function almost normally. Only when those last remaining nerve cells begin to die do symptoms really become pronounced - and at that point, the process is irreversible. Alzheimer's Disease specifically affects the cerebral cortex (gray matter) of the temporal lobe (controlling memory, hearing, language), parietal lobe (language and senses of touch, pain, space, and temperature), and frontal lobe (reasoning, judgment, personality, movement, speech) of the brain, but also deeper structures of the brain, such as the hippocampus (short-term memory) and amygdala (emotional drives).
While death of brain cells is a normal process of aging and can cause mild forgetfulness and slowed reflexes as we age, what causes the accelerated death of brain cells in Alzheimer's Disease patients is currently unknown. What is clear is that the disease does not have a single underlying cause, but rather is due to a number of factors - both environmental and genetic. However, we are gradually beginning to understand exactly what are the factors involved. Multiple studies have shown that the risk for acquiring the disease is age-dependent. The risk is also increased in the presence of family history, indicating that genetic factors play a strong role. However, the nature of this genetic contribution has been difficult to dissect, due to a variety of technical reasons, including the absence of definitive antemortem diagnostic tools. Inheritance patterns also appear to differ between the early-onset and late-onset varieties of the disease; the former resembles an autosomal dominant inheritance with age-dependent penetrance while the latter has a pattern resembling a high-frequency, low-penetrance, single gene disorder or a multifactorial model with multiple genes and/or non-genetic factors. The genetic component in the etiology of the disease also appears to be variable for different families - strong in some and weak in others.
What triggers the formation of plaques and tangles is unknown, although there are several possible candidates. Inflammation of the brain may play a role in their development, and use of nonsteroidal anti-inflammatory drugs (NSAIDs) seems to reduce the risk of developing Alzheimer's disease. Restriction of blood flow may be part of the problem, perhaps accounting for the beneficial effects of estrogen, which increases blood flow in the brain, among its other effects. Highly reactive molecular fragments called free radicals damage cells of all kinds, especially brain cells, which have smaller supplies of protective antioxidants thought to protect against free radical damage. Vitamin E is one such antioxidant, and its use in Alzheimer's disease may be of possible theoretical benefit.
Several genes have been implicated in Alzheimer's disease, including the gene for amyloid precursor protein, or APP, responsible for producing amyloid. Mutations in this gene are linked to some cases of the relatively uncommon early-onset forms of Alzheimer's disease. Other cases of early-onset Alzheimer's disease are caused by mutations in the gene for another protein, called pre-senilin. Alzheimer's disease eventually affects nearly everyone with Down syndrome, caused by an extra copy of chromosome 21. Other mutations on other chromosomes have been linked to other early-onset cases.
Potentially the most important genetic link was discovered in the early 1990s on chromosome 19. A gene on this chromosome, called apoE, codes for a protein involved in transporting lipids into neurons. ApoE occurs in at least three forms, called apoE2, apoE3, and apoE4. Each person inherits one apoE from each parent, and therefore can either have one copy of two different forms, or two copies of one. Compared to those without ApoE4, people with one copy are about three times as likely to develop late-onset Alzheimer's disease, and those with two copies are almost four times as likely to do so. Despite this important link, not everyone with apoE4 develops Alzheimer's disease, and people without it can still have the disease. Why apoE4 increases the chances of developing Alzheimer's disease is not known.
While the ultimate cause or causes of Alzheimer's disease are still unknown, there are several risk factors that increase a person's likelihood of developing the disease. The most significant one is, of course, age; older people develop Alzheimer's disease at much higher rates than younger ones. Another risk factor is having a family history of AD, Down syndrome, or Parkinson's disease. People who have had head trauma or hypothyroidism may manifest the symptoms of AD more quickly. No other medical conditions have been linked to an increased risk for AD.
Many environmental factors have been suspected of contributing to AD, but population studies have not borne out these links. Among these have been pollutants in drinking water, aluminum from commercial products, and metal dental fillings. To date, none of these factors has been shown to cause AD or increase its likelihood. Further research may yet turn up links to other environmental culprits, although no firm candidates have been identified.
More information on dementia (Alzheimer's disease, vascular dementia, lewy body dementia, Pick's disease)
What is dementia? - Dementia is a deterioration of intellectual function and other cognitive skills. Dementia may involve progressive deterioration of thinking, memory, behavior, personality and motor function.
What types of dementia are there? - Types of dementia include Alzheimer's dementia, vascular dementias, Parkinson disease, Lewy body dementia, alcohol-related dementia, and Pick disease.
What're the risk factors for dementia? - The main risk factor for dementia is age. People who have sustained serious head injuries through boxing are prone to dementia pugilistica.
What causes dementia? - Dementia is caused by degeneration in the cerebral cortex including death of brain cells, conditions that impair the vascular or neurologic structures of the brain.
What're the symptoms of dementia? - The early symptom of dementia is diminished short-term memory. Patients with severe dementia cannot perform activities of daily living.
How is dementia diagnosed? - Diagnosis of dementia begins with a thorough physical exam and complete medical history, and followed by information-concentration-orientation test of Blessed et al. and the mini-mental state exam of Folstein et al.
What's the treatment for dementia? - The goal of treatment is to control the symptoms of dementia. Treatment of dementia begins with treatment of the underlying disease.
What's the long term dementia care? - Long-term dementia care may be needed for some patients with dementia. Possible options include in-home care, boarding homes, adult day care, and convalescent homes.
What's alcohol-related dementia? - Alcohol related dementia is a form of dementia related to the excessive drinking of alcohol. Alcohol abuse can lead to several forms of dementia.
What's frontal lobe dementia? - Frontal lobe dementia is a set of degenerative diseases producing many of the same symptoms as vascular dementia. The frontal lobe governs people's mood and behaviour.
What's senile dementia? - Senile dementia is the mental deterioration (loss of intellectual ability) that is associated with old age. Senile dementia is often used when referring to Alzheimer's disease.
What's early onset dementia? - Early onset dementia is a term that covers a range of diseases affecting memory and thinking in people under the age of 65.
What's AIDS related dementia? - HIV associated dementia (HAD) is comprised of a spectrum of conditions from the mild HIV-1 motor cognitive-motor disorder to severe and debilitating AIDS dementia.
What's Alzheimer's disease? - Alzheimer's disease is a form of degenerative brain disease resulting in progressive mental deterioration with disorientation, memory disturbance and confusion.
What types of Alzheimer's disease are there? - Types of Alzheimer's disease include early onset Alzheimer's, late-onset Alzheimer's, and familial Alzheimer's disease (FAD).
What're the stages of Alzheimer's disease? - Stages of Alzheimer's disease include no cognitive impairment, mild cognitive decline, moderate cognitive decline, moderately severe cognitive decline...
What causes Alzheimer's disease? - The ultimate cause or causes of Alzheimer's disease are still unknown, there are several risk factors that increase a person's likelihood of developing the disease.
What're the risk factors for Alzheimer's disease? - The risk for Alzheimer's disease increases with age. People with a family history of Alzheimer's have a greater risk.
What're the warning signs of Alzheimer's disease? - The warning signs of Alzheimer's disease include memory loss, difficulty performing familiar tasks, problems with language, poor or decreased judgment.
What're the symptoms of Alzheimer's disease? - The symptoms of Alzheimer's disease include memory lapses, perform routine tasks, loss of judgment, and personality or behavior changes.
How is Alzheimer's disease diagnosed? - Diagnosis of Alzheimer's disease is complex. Diagnosis of Alzheimer's disease begins with a thorough physical exam and complete medical history.
What's the treatment for Alzheimer's disease? - Some treatments for Alzheimer's disease that can be used to help manage and ease the symptoms. Medications help alleviate the symptoms of depression, anxiety, and delusions.
What medications treat Alzheimer's disease? - Four medications, tacrine, donepezil, rivastigmine tartrate and galantamine, are used to improve intellectual function in some patients with Alzheimer's disease.
What's the dietary therapy for Alzheimer's disease? - Dietary therapy for Alzheimer's disease involves appropriate intake of darkly colored fruits and vegetables, soy, alcohol, folate and vitamin B12.
What's the exercise therapy for Alzheimer's disease? - Aerobic exercise is very important for helping to protect against mental decline during aging due to Alzheimer's disease.
What's the prognosis of Alzheimer's disease? - A person with Alzheimer's disease lives an average of eight years and as many as 20 years or more from the onset of symptoms.
What's vascular dementia? - Vascular dementia is a common form of dementia in older persons that is due to cerebrovascular disease, usually with stepwise deterioration.
What types of vascular dementia are there? - There are a number of different types of vascular dementia. Two of the most common are multi-infarct dementia, binswanger's disease.
What's multi-infarct dementia? - Multi-infarct dementia is the most common form of vascular dementia. Multi-infarct dementia is associated with atherosclerosis.
What is Binswanger's disease? - Binswanger's disease is a progressive neurological disorder characterized by injuries to the blood vessels supplying the deep white-matter of the brain.
What causes vascular dementia? - Vascular dementia can be caused in several different ways. Most commonly there is blockage of small blood vessels (arteries) deep within the brain.
What're risk factors for vascular dementia? - The risk factors for vascular dementia are high blood pressure, high cholesterol, diabetes and heart rhythm problems.
What're the symptoms of vascular dementia? - Symptoms of vascular dementia include memory loss, difficulty doing usual daily activities, and a tendency to wander.
How is vascular dementia diagnosed? - Vascular dementia is diagnosed based on history, symptoms, signs, and tests, and by ruling out other causes of dementia.
What's the treatment for vascular dementia? - Treatment of vascular dementia is aimed at reducing the risk factors including stroke, high blood pressure, diabetes, high cholesterol and heart disease.
What's lewy body dementia? - Lewy body dementia is a progressive cause of dementia characterised by both cognitive problems and motor impairments.
What causes lewy body dementia? - Lewy body dementia is caused by abnormal microscopic deposits of protein in nerve cells. Lewy bodies appear in deteriorating nerve cells.
What're the symptoms of lewy body dementia? - Symptoms of lewy body dementia include a gradual loss of mental abilities, including orientation and memory, reasoning and intelligence.
How is lewy body dementia diagnosed? - Lewy body dementia is diagnosed by taking a careful history of the pattern of symptoms, and by excluding other possible causes.
What's the treatment for lewy body dementia? - There's no specific treatment for lewy body dementia. Treatment is directed at managing the signs and symptoms of the disease.
What is Pick's disease? - Pick disease is a brain disorder that causes slowly worsening decline of mental abilities. Pick's disease is a less common type of dementia.
What causes Pick's disease? - Pick's disease is a rare disorder similar to senile dementia/Alzheimer's type. Behavioral changes are prominent with loss of inhibition.
What're the symptoms of Pick's disease? - The signs and symptoms of Pick's disease include loss of intellectual abilities and changes in behavior and personality.
How is Pick's disease diagnosed? - Diagnosis of Pick's disease is based on initial diagnosis on history and symptoms, signs, and tests, and by ruling out other causes of dementia.
What's the treatment for Pick's disease? - There is no proven effective treatment for Pick's disease. Monitoring and assistance with self-care may be required.