The Causes And Treatment Of Alzheimer's Disease

What is alzheimers disease?

Alzheimer's disease (AD) is a neurodegenerative disease that occurs in people in their most common form over the age of 65 and is responsible for about 60 percent of the world's approximately 24 million dementias.

Causes of alzheimers disease

To date, the cause of Alzheimer's disease is not fully understood.

Genetic risk factors
At the genetic level, a variation in the gene encoding the ApoE has been identified which is a risk factor for the development of Alzheimer's disease. In addition, causal mutations were found in three different genes (presenilin-1 and -2 and amyloid precursor protein (APP, amyloid precursor protein)), and thus the risk of rare early-onset subtype. The changes in all three genes lead to accumulate earlier than in the non-hereditary-sporadic form large amounts of beta-amyloid in the brain. Their share in the development of Alzheimer's disease (population attributable risk fashionable) is estimated to be a maximum of 30%. In a study of 1700 Icelandic patients a natural mutation in the APP gene was discovered, which was associated with the absence of Alzheimer's and dementia.

There is a genetic component in the causation of Alzheimer's disease. Approximately five to ten percent of these patients show a familial aggregation [Familial Alzheimer's disease (FAD)], the mutations of presenilin-1 gene on chromosome 14, the presenilin 2 gene on chromosome 1 or the APP gene on chromosome 21 are due. In addition, an unclear yet connection between Alzheimer's disease and the allele ε4 of apolipoprotein E (ApoE), a protein involved in cholesterol transport, can be produced.

Down's syndrome with its triple system of genetic material of chromosome 21, on which the APP gene is located, also increases the risk of developing dementia, possibly Alzheimer's disease cancer, wherein the detection in people with this genome mutation is complicated by a usually present cognitive impairment.

Furthermore, a mutation variant of the SORL1 gene has been named as an increased risk factor for this disease.

Inflammatory processes or infection
The Nun Study by David Snowdon shows a strong deviation of the pathological brain-finding (multiple Alzheimer's plaques) and repeatedly raised mental performance during his lifetime. Pat McGeer suspected inflammatory processes in the brain as the cause of the disease. Thomas Bayer regards the causal processes in the nerve cells.

Beta-amyloid proteins exhibit a strong antimicrobial activity in vitro. One guess is that they arise as a defensive response in an unknown infection.

Cholesterol risk factors, trauma, diabetes and high blood pressure
Risk factors apply - in addition to the inevitable aging and genetic disposition - a previous Traumatic brain injury, metabolic diseases - Insulin resistance and hyperinsulinemia, diabetes and high cholesterol levels as well as diseases of the cardiovascular system - high blood pressure and suffered strokes.

Aluminum in the brain: sequence or cause of Alzheimer's?
Aluminum was repeatedly brought controversy as a factor associated with Alzheimer's disease in combination. It is a common element among others and of course arises as a trace element in food and drinking water. Additional exposures result from the use in, for example, deodorants and aluminum cookware.

In one incident with aluminum sulfate in drinking water at Camelford in Cornwall, England, in July 1988, a number of people drank water with larger concentrations of aluminum sulfate. The investigations of the long-term health effects after this incident are still not completely finished, but it was found particularly strongly increased aluminum concentrations in the brains of victims in post-mortem examination and further investigation commissioned to determine whether there is a connection with Cerebral amyloid angiopathy.

in the French PAQUID cohort of 1999 and subsequent updates a possible link between aluminum inclusions was prepared by contaminated drinking water and the likelihood of developing Alzheimer's disease. Accordingly, many senile plaques were found with elevated aluminum levels in the brains of Alzheimer's patients.

After a literature study of Ferreira et al. presented from 2008 of 34 relevant studies, 68% is a connection between aluminum and Alzheimer ago, while 8.5% showed no association. 23.5% did not reach a significant result.

The UK Alzheimer's Society, based in London representing 30 January 2009 the medical and scientific view that the studies produced until 2008 did not prove a causal relationship between aluminum and Alzheimer's disease convincing

A health assessment of the Federal Institute for Risk Assessment (BfR) from 2005 saw no connection between the aluminum intake from food commodities and Alzheimer's disease, nor an update in 2007, however, the recommendation was issued as a precaution no acidic foods in contact with keep aluminum pots or foil. The results of an opinion of the European Food Safety Authority (EFSA) to aluminum as a food ingredient (in the fabric E131), which was published in April 2013 are included in a new opinion of the BfR. Again, it is noted that the relationship to Alzheimer's disease is not yet proven, but the estimated intake of aluminum when used daily aluminum-containing antiperspirants lies above the tolerable weekly amount of EFSA.

Prevention of disease

Research in future vaccines
Intended for a vaccination that can prevent the disease or at least prevent the progression of the disease, is widely researched.

So a beta-amyloid immunotherapy based on the monoclonal antibody bapineuzumab is already being studied in clinical trials. The US company Johnson & Johnson and Pfizer have, however, announced in August 2012 that they discontinue the development of bapineuzumab. The monoclonal antibody, which should remove the beta-amyloid from the brain of patients with dementia, has not met in a second Phase III study expectations.

A Göttingen research group demonstrated that vaccination with the new monoclonal antibody (9D5) in mice prevents the progression of the disease. This antibody is directed against a specific molecular structure in the brain and prevents them from producing the protein pyroglutamate Abeta. This protein forms toxic clumps (oligomers) that accumulate in the nerve cells and blood vessels of the brain of Alzheimer's sufferers and so cause the disease-causing damage. An application in humans is the subject of further investigations.

Blood pressure, exercise, nutrition and environmental factors
Various preventive countermeasures against common diseases of civilization seem to reduce the likelihood of developing Alzheimer's disease. The data and scientific acceptability of various food supplements, guidelines for behavior and food ideas, environmental influences and First diseases as the cause of the disease is different. It is important that measures are able to prevent the onset of disease, are not necessarily capable of influencing the course of a previously diagnosed Alzheimer's disease favorable. There are many observational studies, but few controlled randomized proving the effectiveness of the measures. By 2006, a significant reduction in Alzheimer's risk was found for these strict study criteria for the control of blood pressure. Just missing until today but also proven preventive medicine.

Sufficient exercise, a healthy diet with a high proportion of phytochemicals such as the antioxidant quercetin, unsaturated fatty acids, B vitamins - especially folic acid - and avoiding smoking can have a positive effect. The vitamins folate, B6 and B12 build the toxic amino acid homocysteine into harmless substances from. Scientific studies have shown that homocysteine is a key triggers of atherosclerosis and causes aging of the brain strengthened: People with high homocysteine levels have twice the risk of developing Alzheimer's disease. In addition, a low vitamin B12 levels is associated with a greater Hirnatrophierate. The Atrophierate the brain of patients with mild cognitive impairment can, however, be reduced by 29.6 percent by treatment with folic acid, vitamin B12 and B6. In the follow-up study of January 2013, the scientists of Oxford found university that significantly slowed by the external supply of high-dose vitamin B12 in conjunction with folic acid, the reduction in brain volume in people at increased risk of Alzheimer's compared to the control group over a period of two years could be.

David Smith, professor emeritus of pharmacology at Oxford University, who led the study, said: "It's a great effect, much bigger than we had dared to dream." A high level of education seems to be as low as mentally challenging activities. Frequent television consumption is, however, suspected to increase the risk of Alzheimer's. High blood pressure should be detected as early as possible and well treated to reduce the risk of dementia. Scientific studies (Beyreuther et al.) Have shown that elevated cholesterol levels, the risk of developing Alzheimer's disease increases.

According to Berliner Zeitung there should be evidence that caffeine (coffee, tea, etc.) protective effect against the development of Alzheimer's disease.

Antioxidants, green and black tea
In vitro studies have shown that the antioxidant epigallocatechin gallate (EGCG) of green tea can prevent the formation of plaque. Other studies suggest that EGCG may also dissolve the plaques. In animal studies with mice it has been shown that after six months of EGCG treatment, the plaque burden in the cortex, hippocampus and entorhinal cortex was reduced by 54% each, 43% and 58%. Another study that examined the effect of EGCG on Alzheimer's disease, is performed at the Charité in Berlin. Studies from 2011 showed that Theaflavinbestandteile of black tea also prevent the formation of plaques and can dissolve existing plaques.

Medical treatment of sick people

Alzheimer's disease can not currently be cured. The positive effect of the currently approved for the treatment of dementia drugs on existing symptoms is relatively small, they can not stop the progression of the disease. In 2006 was published by the American Association for Geriatric Psychiatry consensus paper on Alzheimer's treatment. After a preclinical study from Case Western Reserve University in February 2012, the chemotherapeutic agent bexarotene could dissolve up to 75% of the β-amyloid plaques and symptoms of the disease, such as memory loss revise, in mice. Bexarotene is not approved for the treatment of Alzheimer's disease. Currently, it is unclear whether the compound is effective in humans.

Acetylcholinesterase inhibitors
The drugs ensure that acetylcholine is degraded more slowly in the brain and is present in higher concentration. The aim is the reduction of acetylcholine levels are counteracted by the death of neurons that produce this neurotransmitter. Representatives of this group of active ingredients are galantamine, donepezil, rivastigmine and the active huperzine A, which is currently being investigated clinically. Open to the acetylcholinesterase inhibitors are heavier in mild to moderate Alzheimer's dementia, not included. The effectiveness of the therapy is discussed. In the ideal study it is shown that both the patch formulation and administration of oral rivastigmine significantly compared with placebo improve the cognitive abilities of the patients. There are also studies that show little effect of acetylcholinesterase inhibitors. Under German psychiatrists the extent of the benefits of the preparations is therefore controversial.

Ibuprofen and other nonsteroidal anti-inflammatory drugs
In retrospective studies, was found in 1995 that rheumatic patients have a significantly reduced risk of developing Alzheimer's disease, or develop the disease with them later than non-rheumatics from. It was concluded that the effect of the nonsteroidal anti-inflammatory drugs (NSAID) is (in English-language publications nonsteroidal anti-inflammatory drugs (NSAID) was attributable taking these patients.

In some transgenic animal models, a reduction of beta-amyloid plaques in the administration of ibuprofen was found.

When people are so far no data from randomized double-blind studies showing a secure mode of action of ibuprofen and other nonsteroidal anti-inflammatory drugs. Due to the considerable side effects that can be expected for a permanent prophylactic administration of ibuprofen is not recommended for an uncontrolled intake. The measures necessary for the possible prevention of Alzheimer's disease doses of nonsteroidal anti-inflammatory drugs are considerably higher than the normal treatment of pain. The NSAID are suspected to cause cardiovascular problems when they are taken on time and in high doses.

With ibuprofen and derivatives of ibuprofen currently running a series of clinical trials in Alzheimer's patients.

Activation of ABC transporters
New research by Jens Pahnke (University of Rostock) and the out of him, "Neurodegeneration Research Lab" (NRL) to show that through the use of thiethylperazine and thiethylperazine derivatives with ABC transporter-activating effect of a treatment of neurodegenerative diseases, as well as the function the transporter ABCC1 for diagnosis and treatment monitoring of Alzheimer's disease (Parkinson and M.) is possible. By these agents the course of Alzheimer's disease and Parkinson's disease can be delayed by several years. This means a substantial increase in ongoing quality of life for patients and cost savings for the health system. The active ingredient patent pending by the University of Rostock is a second indication for an already available on the market drug (Torecan®). Pahnke published these results in the "Journal of Clinical Investigation."

NMDA-receptor antagonist
The effect of the neurotransmitter glutamate, the most common excitatory neurotransmitter in the central nervous system, which is involved in learning and memory functions, was approved in Europe in 2002 and in the US in 2003. The previously only representative of this class of drugs is memantine. This is a NMDA receptor (N-methyl-D-aspartate) antagonist and to normalize the disturbed in Alzheimer's dementias glutamatergic signal transmission. Study results show that memantine after six months leading moderate to severe disease in an overall slight improvement in cognitive disorders and impaired activities of daily living. Memantine is approved for moderate to severe Alzheimer's dementia, not for light.

Vitamin E
A new randomized clinical study shows that vitamin E may slightly delay the progress of care in high doses. In contrast, the anti-dementia drug memantine has disappointed in this study. The primary endpoint was the ADCS-ADL (Alzheimer's Disease Cooperative Study - Activities of Daily Living), which captures daily living skills. Vitamin E was the fall of the ADCS-ADL somewhat delayed, although significance was only reached after an adjustment. In addition died of 613 participants 128 prior to the conclusion of the study. The study thus joins a series studies with different conclusions about the effectiveness of vitamin E in Alzheimer's disease a. Because of the small effect and the possible increased mortality, high-dose vitamin E can - Gabe therefore not generally recommended.

Psychotherapeutic treatment
Symptoms such as anxiety, depression or agitation and aggression that may occur in the course of the disease can be treated with the help of psychotherapy and psychotropic drugs. In addition, non-pharmacological interventions for behavioral disturbances of dementia are favored since the beginning of the 21st century increasingly.

Code of Conduct
An American study found that people who had exercised a little mentally challenging activity between their 20th and 50th year, often developing Alzheimer's disease. It is possible that the threshold at which symptoms become apparent set up.

Let Current scientific suspect that even slight but regular physical activity (walking, gardening) might against the development of Alzheimer's dementia protect. It is believed that the positive effects of exercise on vascular risk factors (hypertension, dyslipidemia and diabetes mellitus) reduce vascular-related damage in the brain, thus - indirectly - impede the onset of dementia symptoms.

The adaptation of habitats to the changing needs and capacities can facilitate the daily lives of patients and caregivers. The simplification of work processes and the labeling of objects help the patient to receive a higher level of independence. Changes in the known processes or environment stimulate the patient often unnecessary, while well-lit rooms, adequate rest and limited requirements give the patient a feeling of security. Appropriate social and visual stimulation can lead to an improvement in attention and focus, for example, an increase in food intake can be achieved when strikingly colored table accessories are used, the Alzheimer's patients to exercise better with reduced contrast detection.

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