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Alzheimer's disease
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Alzheimer's disease

Alzheimer's disease (AD) or senile dementia of Alzheimer's type is a disorder or loss of mental functions resulting from brain tissue changes; the causes are yet to be fully elucidated (mutations in at least four genes predisposing to AD have been identified). There are also studies that link aluminium to the progression of Alzheimer's, but the results are far from conclusive.

The disease was thought to be uncommon, until the 1960s when it was realized that much of what had been regarded as the normal process of aging was actually the result of this disease.

Table of contents
1 Clinical features
2 Pathology
3 Etiology
4 Prevalence
5 Diagnosis
6 Treatment
7 Nutrition and Alzheimer's
8 Genetic and population effects
9 Social issues
10 History
11 Famous Alzheimer's sufferers
12 See also
13 External links

Clinical features

The typical visible symptom is progressive and chronic memory loss. Alzheimer's disease is also manifested in behavorial changes, which may include confusion, disorientation, sudden periods of defiance, abusive behavior, or violence, etc. in people who have no previous history of such behavior (rarely, an affected person experiences euphoria). Thus, Alzheimer's disease presents a problem in patient management, as well. Average duration is approximately 10 years.


There are several changes found in the brain in AD.

These features are seen down the microscope using histology and can only be determined post mortem.


Three competing hypotheses exist to explain the cause of the disease.

The oldest hypothesis is the "cholinergic hypothesis". It states that Alzheimer's begins as a deficiency in the production of acetylcholine, a vital neurotransmitter. Much early therapeutic research was based on this hypothesis, including restoration of the "cholinergic nuclei". The possibility of cell-replacement therapy was investigated on the basis of this hypothesis. All of the first-generation anti-Alzheimer's medications are based on this hypothesis and work to preserve acetylcholine by interfering with acetylcholinesterases (enzymes that break down acetylcholine). Results had from these medicines have not been promising. In all cases, they have served to only slow the progress of the disease and have neither halted nor reversed it. These results and other research have led to the conclusion that acetylcholine deficiencies may not be causal but are a result of widespread brain tissue damage, damage so widespread that cell-replacement therapies are likely to be impractical.

The other two hypotheses are of generally equal acceptance. "Tau-ists" believe that the tau protein abnormalities come first and lead to a full disease cascade. "bA-ptists" believe that beta amyloid deposits are the causative factor in the disease. For example, the presence of the APP gene on chromosome 21 is believed to explain the high incidence of AD in patients with Down's syndrome (trisomy 21).. The terms "tau-ist" and "ba-ptist" are used (lightheartedly) in scientific publications by Alzheimer's disease researchers. A third protein, alpha synuclein, which has already been shown to be important in Parkinson's disease, has recently been proposed as the etiological candidate, giving rise to the "syn-ners". By 2004, several researchers have come to the conclusion that Alzheimer's disease may be a "triple-protein pathology", wherein interactions among all three lesions are what give rise to Alzheimer's disease, rather than any one of the three.

There is compelling evidence that genetic predispositions underlie the development of Alzheimer's disease. However, the most obviously genetic cases are also the rarest. Most cases identified are 'sporadic' with no clear family history. It is probable that environmental factors have to interact with a genetic susceptibility to cause development of disease. Head injury has been consistently shown to be linked to later development of AD in epidemiological studies. In addition, small cranial diameter has been shown to correlate well with early onset of recognizable symptoms. The most commonly accepted explanation for this last feature is that larger brains simply may have more cells that can afford to be lost. Inheritance of a specific variation the ApoE gene (epsilon 4) is regarded as a risk factor for development of disease, but large-scale genetic association studies raise the possibility that even this does not indicate susceptability so much as how early one is likely to develop Alzheimer's. Intriguing work is currently going on investigating the possibility that the regulatory regions of various Alzheimer's associated genes could be important in sporadic Alzheimer's, especially inflammatory activation of these genes.

Studies have not shown strong link with toxins, vitamins, metals or diet, although rabbits fed a high-cholesterol diet in the presence of copper ions in their water did develop amyloid brain lesions and cognitive deficiencies [1], [1]. Likewise, linkage has been found between zinc or copper and reactive oxidative stress contributing to Alzheimer's pathology [1], and the amyloid precursor protein has been shown to alter expression in response to metal supplementation and chelation [1], [1], [1]. Therefore, it is hasty and premature to dismiss any and all environmental effects out of hand.

Rare cases are caused by dominant genes that run in families. These cases often have an early age of onsent. Mutations in presenilin-1 or presenilin-2 genes have been documented in some families. Mutations of presenilin 1 (PS1) lead to the most aggressive form of familial AD (FAD). Evidence from rodent studies suggests that the FAD mutation of PS1 results in impared hippocampal-dependent learning which is correlated with reduced adult neurogenesis in the dentate gyrus (Wang et al, 2004). Mutations in the APP gene on chromosome 21 can also cause disease.


Alzheimer's disease is the most frequent reason for dementia in the elderly and affects almost half of all patients with dementia.

3-10% of persons aged 65 show signs of the disease, while 50% of persons aged 85 have symptoms of Alzheimer's. The proportion of persons with Alzheimer's begins to decrease after age 85 because of the increased mortality due to the disease, and relatively few people over the age of 100 have the disease.


Unfortunately, a definitive diagnosis of Alzheimer's disease must await an autopsy, at present. Many increasingly sophisticated diagnostic tests have been proposed (including: brain scans, behavioral tests and testing for genetic predisposition) but these are at present used to identify or rule out possible alternative explanations of the symptoms.

Psychological testing generally focuses on memory, attention, abstract thinking, the ability to name objects, and other cognitive functions. However, results of psychological tests do not easily distinguish between Alzheimers Disease and other types of dementia. Psychological testing can be helpful in establishing the presence of and severity of dementia. It 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.


There is no cure, although there are drugs which reduce neurotransmitter degradation and delay the symptoms of the disease. Non-steroidal anti-inflammatory drugs (including ibuprofen, acetaminophen, and aspirin) also seem to slow progress of the disease, according to clinical trials, but the mechanism is not understood.

There are ongoing tests of an Alzheimer's disease vaccine. This was based on the idea that if you could reverse deposition of amyloid you would stop the disease. Initial results in animals were promising. However when the first vaccines were used in humans, brain inflammation resulted and the trials were stopped. It is hoped that research will provide a better formulation and that in the future it can be of use in families with history of Alzheimer's Disease.

Anticholinesterase-inhibition treatment is important because there is selective loss of forebrain cholinergic neurons as a result of Alzheimer's. AChE-inhibitors reduce the rate at which ACh is broken down and hence increase the prevelence of ACh in the brain (combatting the loss of ACh caused by the death of the cholinergin neurons). Here are some examples of some drugs:

tetrahydroaminoacridine (THA or Tacrine) - Modest improvement in memory and cognition in 40% of cases. Must be taken four times a day. The treatments causes nausea cramps and is hepatotoxic
donepezil - Single daily dosage, slightly less side effects than tacrine but no efficacy increase.
rivastigmine - Has shown the most effective improvement in cognition, although does also induce nausea and vomiting.
Anticholinesterase inhibitors treat symptoms but do not prevent cell death!

Nutrition and Alzheimer's

Some work is being done to investigate the role of raised levels of homocysteine, and possible nutritional prevention or treatment through taking of foods high in B vitamins and antioxidants to control the levels of homocysteine.

This view is supported by Teodoro Bottiglieri, a neuropharmacologist at the Baylor Institute of Metabolic Disease in Dallas, Texas, and Andrew Mc Caddon, a researcher at the University of Wales. (See the Times newspaper, January 31 2004 "Could vitamins help delay the onset of Alzheimer?s?" by Jerome Burne).

A study (Archives of Neurology 2004;61:82-88) has reported that vitamins E and C might reduce the risk of Alzheimer's disease.

See also: Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002 Feb 14;346(7):476-83.

Recent studies have shown that non-steroidal anti-inflammatory drugs (NSAIDS) like Aspirin and Ibuprofen can delay the onset of Alzheimer´s disease. Presently there are also studies going on testing cholesterol-lowering drugs, so-called statins, like simvastatin etc. as a means of preventing or delaying Alzheimer´s. There seems to be a connection between the cholesterol level inside the brain cells and the deposition of toxic amyliod plaques which make the brain cells die.

Genetic and population effects

Various gene alleles have been associated with Alzheimer's disease, most notably the apolipoprotein E (ApoE) gene. ApoE normally functions to regulate cholesterol metabolism. In addition, it has recently been discovered that Chinese and North American populations differ significantly in development of full-fledged Alzheimer's from early warning symptoms. Whether the reason for this is genetic, dietary, or social has yet to be investigated.

Social issues

Alzheimer's is considered to be a major public health challenge since the average age of the industrialized world's population is increasing.


The symptoms of the disease as a distinct nosologic entity were first identified by Emil Kraepelin, and the characteristic neuropathology was first observed by Alois Alzheimer in 1906. In this sense, the disease was co-discovered by Kraepelin and Alzheimer, who worked in Kraepelin's laboratory. Because of the overwhelming importance Kraepelin attached to finding the neuropathological basis of psychiatric disorders, Kraepelin made the generous decision that the disease would bear Alzheimer's name (J. Psychiat. Res., 1997, Vol 31, No. 6, pp. 635-643).

Famous Alzheimer's sufferers

See also

External links