Alzheimer's disease (AD) or senile Dementia (from Latin demens) is progressive decline in cognitive function due to damage or disease in the brain beyond what might be expected from normal aging. Particularly affected areas may be memory, attention, language and problem solving, although particularly in the later stages of the condition, affected persons may be... dementia of Alzheimer's type is a neurodegenerative disease which results in a loss of mental functions due to the deterioration of In the anatomy of animals, the brain, or encephalon, is the supervisory center of the nervous system. Although the brain is usually cited as the supervisory center of vertebrate nervous systems, the same term can also be used for the invertebrate central nervous system. In most animals, the brain is... brain Biological tissue is a group of cells that perform a similar function. The study of tissues is known as histology, or, in connection with disease, histopathology. The classical tools for studying the tissues are the wax block, the tissue stain, and the optical microscope, though developments in electron microscopy, immunofluorescence... tissue. Its exact Etiology (alternately aetiology, aitiology) is the study of Greek words aitia = cause and logos = word/speech) is used in philosophy, physics and biology in reference to the causes of various phenomena. It is generally the study of why things occur, or even the reasons behind the way that things act... aetiology (cause) is still unknown, but environmental as well as genetic factors are thought to contribute ( This article is about mutation in biology, for other meanings see: mutation (disambiguation). Mutations are permanent, transmissible changes to the genetic material (usually DNA or RNA) of a cell. Mutations can be caused by copying errors in the genetic material during cell division and by exposure to radiation, chemicals, or... mutations in at least four This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). Introns are regions often found in eukaryote genes which are removed in the splicing process: only the exons encode the protein. This diagram labels a region of only 40... genes predisposing to AD have been identified).

Until the Centuries: 19th century - 20th century - 21st century Decades: 1900s 1910s 1920s 1930s 1940s 1950s - 1960s - 1970s 1980s 1990s 2000s 2010s Years: 1960 1961 1962 1963 1964 1965 1966 1967 1968 1969 Events and trends The 1960s was a turbulent decade of change around the world. Many of the trends of... 1960s, the disease was thought to be uncommon, but later it was realized that much of what had been regarded as the normal process of In biology, senescence is the state or process of aging. For the social, cultural, and economic aspects see ageing. The word senescence is derived from the Latin word senex, meaning old man or old age. Cellular senescence is a phenomenon where isolated cells demonstrate a limited ability to divide in... aging was actually the result of this disease.

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 considerable problem in patient management, as well. Average duration is approximately 10 years. The disease duration has been noted to vary as very roughly half of the normal life expectancy of a healthy person of the same age as the patient in whom the Alzheimer's is diagnosed, subject to a maximum of 10 to 12 years for those diagnosed at a young age.

Pathology

There are several changes found in the brain in AD.

• The deposition of an abnormal protein outside nerve cells in the form of Amyloid describes various types of protein aggregations that share specific traits when examined microscopically. The name amyloid comes from the early mistaken identification of the substance as starch (amylum in Latin), based on crude iodine-staining techniques. For a period the scientific community debated whether or not amyloid deposits were... amyloid. These are called diffuse plaques and amyloid also forms the core of more organized plaques called senile or neuritic plaques.

• The accumulation of abnormal filaments of protein inside nerve cells in the brain. The protein is called tau and is normally present to stabilise microtubules. In AD, an abnormally phosphorylated form of tau protein accumulates as paired helical filaments. Tau accumulates
  • As masses of filaments inside nerve cell body termed neurofibrillary tangles
  • Inside nerve cell processes in the brain termed neuropil threads
  • Inside nerve cell processes that surround amyloid plaques - termed plaque neurites.

• Amyloid accumulation in the walls of small blood vessels in the brain. Termed amyloid angiopathy (also called congophilic angiopathy)

• Diffuse neuropathology, nerve cells and their processes including synapses die and are lost from key brain regions. This results in Atrophy is the partial or complete wasting away of a part of the body. The causes of atrophy would include poor nourishment, poor circulation and loss of nerve supply to the target organ. Since atrophy is a general physiological process of reabsorption and breakdown of tissues, a certain amount of... atrophy of the affected areas and enlargement of the ventricles.

• Loss of synaptic contacts between neurons. May be related to the regulation of Schematic of cell adhesion The study of cell adhesion is part of cell biology. Cells are often not found in isolation, rather they tend to stick to other cells or non-cellular components of their environment. A fundamental question is: what makes cells sticky? Cell adhesion generally involves protein molecules... cell adhesion proteins by presenilins. The presenilins have been identified as part of the processing apparatus that produces the amyloid beta protein.

There is also regional involvement of gross atrophy, and enlarged ventricles in the brain. Massive synaptic and dendritic loss is expected. The neurotransmitters Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesised in serotonergic neurons in the central nervous system and enterochromaffin cells in the gastrointestinal tract. Serotonin is believed to play an important part of the biochemistry of depression, bipolar disorder and anxiety. It is also believed to be influential... serotonin, The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. It is a chemical transmitter in the central nervous system (CNS) as well as in the parasympathetic nervous system in many organisms including humans. Chemistry Acetylcholine is an ester of acetic acid and choline with... acetylcholine, Norepinephrine, known as noradrenaline outside the USA, is a catecholamine and a phenethylamine with chemical formula C8H11NO3. It is released from the adrenal glands as a hormone into the blood, but it is also a neurotransmitter in the nervous system where it is released from noradrenergic neurons during synaptic transmission... norepinephrine, and Somatostatin is a hormone. Precisely it is mixture of two peptides, one built of 14 amino acids, the other of 28. Somatostatin is secreted not only by cells of the hypothalamus but also by so called delta cells of stomach, intestine and pancreas. It binds to somatostatin receptors. All actions... somatostatin are at decreased levels. Glutamic acid or glutamate is one of the 20 most common natural amino acids. As its name indicates, it is acidic, with a carboxylic acid component to its side chain. Glutamic acid is critical for proper cell function, but it is not considered an essential nutrient in humans because the... Glutamate levels are usually elevated.

Many of these features can be seen with the microscope using special histological techniques and are only seen when the brain is examined after death.

Etiology

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 from these medicines have not been promising. In all cases, they have served to only treat symptoms 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 A child with Down syndrome Down syndrome (also called Downs syndrome) encompasses a number of genetic disorders, of which trisomy 21 (a nondisjunction) is the most representative, causing highly variable degrees of learning difficulties and physical disabilities. This genetic disorder was named after John Langdon-Down, the British doctor... Down 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 is a leap year starting on Thursday of the Gregorian calendar. It was designated the: International Year of Rice (by the United Nations) International Year to Commemorate the Struggle against Slavery and its Abolition (by UNESCO) Elections were held in 73 countries during 2004. See a list of elections... 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 of the ApoE This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). Introns are regions often found in eukaryote genes which are removed in the splicing process: only the exons encode the protein. This diagram labels a region of only 40... 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 susceptibility 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 are organic chemicals that a given living organism requires in trace quantities for good health, but which the organism cannot synthesize, and therefore must obtain from its diet. The term vitamin does not encompass other essential nutrients such as dietary minerals, essential fatty acids or essential amino acids. Nor... 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] (http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12920183), [2] (http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14506299). Likewise, linkage has been found between zinc or copper and reactive oxidative stress contributing to Alzheimer's pathology [3] (http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0V-483ST4V-1&_coverDate=04%2F30%2F2003&_alid=187240288&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4872&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=c4bdc9c6cb9a59aa2a676e79124856d3), and the amyloid precursor protein has been shown to alter expression in response to metal supplementation and chelation [4] (http://iospress.metapress.com/app/home/contribution.asp?wasp=nntr48wqwp5xnjarpv5m&referrer=parent&backto=issue,10,17;journal,1,29;linkingpublicationresults,1:105656,1), [5] (http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCR-4B37JCB-2&_coverDate=01%2F15%2F2004&_alid=187240616&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=5177&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=f8157cd24891e6a93e263dae23299e96), [6] (http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0002-8614&date=2003&volume=51&issue=8&spage=1143). Therefore, it is hasty and premature to dismiss any and all environmental effects out of hand. There have been studies that link General Name, Symbol, Number aluminium, Al, 13 Chemical series poor metals Group, Period, Block 13 (IIIA), 3, p Density, Hardness 2700 kg/m3, 2.75 Appearance silvery Atomic properties Atomic weight 26.981538 amu Atomic radius (calc.) 125 pm (118 pm) Covalent radius 118 pm van der Waals radius no... aluminium to the progression of Alzheimer's, but the results from these studies have not been confirmed and are not widely accepted by Alzheimer's experts.

Rare cases are caused by dominant genes that run in families. These cases often have an early age of onset. 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 The location of the hippocampus in the human brain. The hippocampus is a part of the brain located inside the temporal lobe (humans have two hippocampi, one in each side of the brain). It forms a part of the limbic system and plays a part in memory and navigation. The... hippocampal-dependent learning which is correlated with reduced Neurogenesis literally means birth of neurons. Neurogenesis is most prevalent during pre-natal development and is the process by which neurons are created to populate the growing brain. Adult Neurogenesis Neurons are born in the adult. We know that adult neurogenesis takes place in the olfactory bulb and in the... adult neurogenesis in the The location of the hippocampus in the human brain. The hippocampus is a part of the brain located inside the temporal lobe (humans have two hippocampi, one in each side of the brain). It forms a part of the limbic system and plays a part in memory and navigation. The... dentate gyrus ( Wang et al, 2004 (http://www.sciencedirect.com/science/article/B6T0F-4CB0G5C-B/1/f88958872d2aed83eebc6cbd76f9341f)). Mutations in the APP gene on This article is about the biological chromosome. For information about chromosomes in genetic algorithms, see Chromosome (genetic algorithm). Figure 1: Chromosome. (1) Chromatid. One of the two identical parts of the chromosome after S phase. (2) Centromere. The point where the two chromatids touch, and where the microtubules attach. (3... chromosome 21 can also cause disease.

Prevalence

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

2-3% of persons aged 65 show signs of the disease, while 25% or more of persons aged 85 have symptoms of Alzheimer's and an even greater number have some of the pathological hallmarks of the disease without the characteristic symptoms. 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.

Diagnosis

While expert clinicians who specialize in memory disorders can diagnose AD with an accuracy of 85-90%, a definitive diagnosis of Alzheimer's disease must await an For the former Death Metal band called Autopsy, see Autopsy (band). An autopsy (also known as a post-mortem examination or necropsy) is a medical investigation of a corpse to determine the cause of death. General Information The term autopsy derives from the Greek for to see with ones... autopsy. Many increasingly sophisticated diagnostic tests are also used (including: Brain imaging is a fairly recent discipline within medicine and neuroscience. Brain imaging falls into two broad categories -- structural imaging and functional imaging. The former deals with the overall structure of the brain and the precise diagnosis of intracranial disease and injury. The latter is used for neurological and cognitive... brain scans, behavioral tests and testing for genetic predisposition) but these are, at present, used mainly to identify or rule out possible alternative explanations for 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 Alzheimer's Disease and other types of dementia such as Normal pressure hydrocephalus (NPH) is a neurological disorder often misdiagnosed as Parkinsons disease, Alzheimers disease, and senility. It brings incontinence, difficulty walking (ataxia-like wide-based gait), and memory problems. NPH stems from an accumulation of cerebrospinal fluid around the brain enlarging ventricles and stretching the brains... normal pressure hydrocephalus. 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.

Prevention

Efforts to find a cure Alzheimer's after-the-fact have so far been disappointing. Meanwhile, the apparent great success of preventive strategies remained uncelebrated and almost unnoticed. Age is the primary risk factor for Alzheimer's. The baby boom is approaching its golden years. Indeed, much of the concern about the solvency of the governmental social safety net is founded on estimates of the costs of caring for baby boomers, assuming that they develop Alzheimer's in the same proportions as earlier generations. Most preventive strategies appear to work far better (or at all) only if begun long before the symptoms of overt Alzheimer's appear. Thus wide dissemination of information about the availablility of effective preventive strategies appears a public health strategy of high benefit and high urgency.

Many studies have indicated that non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin delay the onset, and lower the ultimate risk, of Alzheimer´s disease. According to population studies, low but consistent daily NSAID use over a period of years of NSAIDs such as ibuprofen (Advil, Motrin) seems to significantly slow the progress of Alzheimer's, and eventually to dramatically decrease the risk of the disease in those who have not yet developed it. Quite large daily doses of aspirin also appear to slow the progression towards Alzheimer's, and reduce the eventual risk of developing the disease, but to a lesser degree, and with a much greater risk of potentially fatal stomach ulceration. It seems that NSAIDs are of great use in preventing or delaying the onset of the disease but of little use for treating it once it has progressed to early or full-blown Alzheimer's. Daily NSAID users experience greater risk reduction over time, with some reduction after two years of regular ibuprofen use, and marked reduction after five or more years. It should be noted that some similar drugs such as acetaminophen, naproxen, and the ' Cyclooxygenase (COX) is an enzyme that is responsible for formation of important biological mediators called prostanoids (including prostaglandins, prostacyclin and thromboxane). Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain; this is the method of action of well-known drugs such as aspirin and ibuprofen... COX-2 inhibitors' were found to have no demonstrated benefit (and some evidence of cardiac harm). This ineffectiveness and the increase in adverse cardiac events associated with these agents was reported in various studies in 2004 and highlights the key role of ibuprofen in the original studies showing moderated risk associated with NSAID use. These studies leave ibuprofen as the NSAID most likely to reduce Alzheimer's risk. Ibuprofen is also the nonprescription NSAID with the lowest risk of promoting gastrointestinal bleeding and stomach ulcers.

A study (Archives of Neurology 2004; 61:82-88) has reported that the combination of vitamins E and C might, over time, sharply reduce the risk of Alzheimer's disease. Marked reduction (up to 80% risk reduction) was achieved after a period of more than five years, but only if dosage was 400 i.u. per day of vitamin E plus 500 mg or more per day of vitamin C. Lesser amounts, such as those found in multivitamin pills, appeared markedly less effective. Large doses of vitamin E without vitamin C had only a mild effect, while large doses of vitamin C without vitamin E had no benefit. However in one small study, 2000 i.u. per day of vitamin E did appear to delay the progression of early Alzheimer’s by several months. Other evidence suggests that vitamin E becomes a damaging pro-oxidant if given in isolation (without other antioxidants). In isolation vitamin E is not recharged after absorbing a free radical by another antioxidant such as vitamin C or Alpha-Lipoic Acid. Some studies suggest that a ratio of at least 1000 mg of vitamin C to 400 i.u. of vitamin E is ideal. Recent studies suggest that the most common forms of E sold in supplements, the dl-alpha or d-alpha tocopherol form, are of little value, and that the gamma form of vitamin E, or a mixture of all the tocopherols and tocotrienols that collectively make up vitamin E from food, provide the most benefit. Vitamin E is markedly less effective unless taken with oil.

In a number of retrospective studies, regular physical exercise has appeared to be inversely related to the development of Alzheimer’s. The Alzheimer's risk of those exercising regularly was half that of the least active. This research is consistent with the observation that virtually all measures designed to promote cardiac fitness and reduce stroke risk also seem to reduce Alzheimer's risk. However in one study, dance appeared to be the only exercise effective in reducing risk. The presence of cardiovascular risk factors -- diabetes, hypertension, high cholesterol and smoking -- in middle age (ages 40 to 44) was found very strongly associated with late-life dementia, as reported in Neurology 2005;64:277-281.

Improved nutritional status of the B vitamin folic acid was found to reduce Alzheimer's incidence in a study of an order of nuns, many of whom volunteered to have their mental status assessed and donated their brains for study after death. The "Nun's study" also revealed nuns who, in life, showed little or no dementia, but upon autopsy were found to have extensive Alzheimer’s plaques. The unimpaired nuns’ brains were free of evidence of stroke, including micro-strokes. Nuns whose brains revealed both plaques and stroke damage, however, were severely impaired in functioning while alive. Thus avoidance of risk factors for stroke may be a key element in preventing final progression to being disabled by Alzheimer's dementia. The discovery of the co-founding role of stroke supports other research showing that quitting smoking, weight reduction, and avoidance of diabetes all reduce Alzheimer's risk. Diabetes greatly increases Alzheimer's risk, and one factor at work may be that the enzyme charged with removing excess insulin from the blood, the Insulin Degrading Enzyme (IDE), also has the responsibility for removing Beta-amyloid plaques from the brain. Perhaps the excess insulin involved in the pre-diabetic metabolic syndrome, as well as insulin used to treat existing diabetes, may demand more IDE than the body is able to produce, leaving none to remove accumulating beta amyloid plaques from the brain.

Some evidence suggests that Alzheimer's risk may also be reduced by inclusion of fish in the weekly diet.

The spice Binomial name Curcuma longa Linnaeus Turmeric (Curcuma longa, also known as tumeric or curcumin) is a spice commonly used in curries and other south Asian cooking. It is a significant ingredient in most commercial curry powders. Turmeric is also used to give a yellow color to some prepared mustards, canned... turmeric reduces Alzheimer's incidence in a mouse model and actually dissolves human senile plaques in the test tube. Populations on the Indian subcontinent using turmeric regularly in curry dishes have much lower incidence of Alzheimer's than elsewhere. These factors suggest that inclusion of a bit of turmeric or curry spice in the diet may provide preventive value. Turmeric is a powerful antioxidant and a powerful anti-inflammatory.

Presently there are also studies going on testing cholesterol-lowering drugs, so-called statins, like lovastatin, 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 amyloid plaques which make the brain cells die. In addition to lowering cholesterol, the statins may have a beneficial role in reducing inflammation.

The recent observation that nicotine exposure leads to delayed onset of Alzheimer's has stimulated plenty of research into the relationship of nicotine intake and the disease. This is the focus of ongoing debate, and no consensus has been reached.

Nutrition and Alzheimer's

Some work is being done to investigate the role of raised levels of homocysteine, and possible Nutrition is interpreted as the study of the organic process by which an organism assimilates and uses food and liquids for normal functioning, growth and maintenance and to maintain the balance between health and disease. Also included is the idea of an optimal balance of nutrients and whole foods, to... nutritional prevention or treatment through taking of foods high in B vitamins and An antioxidant is a chemical that prevents the oxidation of other chemicals. In biological systems, the normal processes of oxidation (plus a minor contribution from ionizing radiation) produce highly reactive free radicals. These can readily react with and damage other molecules: in some cases the body uses this to fight... 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 The University of Wales is a federal university founded in 1893. It has member institutions in all parts of Wales, ranging from old Red Brick universities such as Aberystywth to post-1992 universities such as UWIC and Newport. The Chancellor of the University of Wales is HRH the Prince of... University of Wales. (See the Times newspaper, January 31 2004 "Could vitamins help delay the onset of Alzheimer's?" by Jerome Burne).

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.

Treatment

There is no cure, although there are drugs which reduce neurotransmitter degradation and alleviate some of the symptoms of the disease.

Acetylcholinesterase inhibitors

In biochemistry, cholinesterase is a term which refers to one of the two enzymes (EC 3.1.1.7): Acetylcholinesterase (AChE), also known as RBC cholinesterase, erythrocyte cholinesterase, or (most formally) acetylcholine acetylhydrolase, found primarily in the blood and neural synapses Pseudocholinesterase, also known as plasma cholinesterase, butyrylcholinesterase, or (most... Acetylcholinesterase (AChE) inhibition was thought to be important because there is selective loss of forebrain A synapse is cholinergic if it uses acetylcholine as its neurotransmitter. The parasympathetic nervous system is entirely cholinergic. A cholinergic agent, also known as a parasympathomimetic is a chemical which functions to enhance the effects mediated by acetylcholine in the central nervous system, the peripheral nervous system, or both. These... cholinergic neurons as a result of Alzheimer's. AChE-inhibitors reduce the rate at which acetylcholine (ACh) is broken down and hence increase the concentration of ACh in the brain (combatting the loss of ACh caused by the death of the cholinergin neurons). Acetylcholinesterase-inhibitors seemed to modestly moderate symptoms but do not prevent disease progression including cell death.

Examples include:

• Tacrine is a parasympathomimetic and a centrally acting cholinesterase inhibitor (anticholinesterase). It was the first centrally-acting cholinesterase inhibitor approved for the treatment of Alzheimers disease, and was first synthesised at the Department of Pharmacology at the University of Sydney. Clinical uses Tacrine was the prototypical cholinesterase inhibitor for... tacrine - no longer clinically-used
• Donepezil, which goes by the trade name Aricept® (Pfizer), is a centrally acting reversible cholinesterase inhibitor. Its main therapeutic use is in the treatment of Alzheimers disease where it is used to increase cortical acetylcholine. It is well absorbed in the gut with an oral bioavailability of 100% and... donepezil
• Categories: Stub | Anticholinesterases | Antidementia agents ... galantamine
• rivastigmine

2004 is a leap year starting on Thursday of the Gregorian calendar. It was designated the: International Year of Rice (by the United Nations) International Year to Commemorate the Struggle against Slavery and its Abolition (by UNESCO) Elections were held in 73 countries during 2004. See a list of elections... Recently, a controversy has erupted about cholinesterase inhibitors because a study by Courtney (2004) in the respected medical journal The Lancet is a British medical journal, published weekly by the Lancet Publishing Group. It takes its name from the surgical instrument called a lancet. The present editor-in-chief is Richard Horton. There are several specialized editions of The Lancet, called The Lancet Neurology, The Lancet Oncology and The... The Lancet has suggested they are ineffective. The pharmaceutical companies dispute the findings of the study.

NMDA antagonists

Recent evidence of the involvement of Glutamic acid or glutamate is one of the 20 most common natural amino acids. As its name indicates, it is acidic, with a carboxylic acid component to its side chain. Glutamic acid is critical for proper cell function, but it is not considered an essential nutrient in humans because the... glutamatergic neuronal excitotoxicity in the Etiology (alternately aetiology, aitiology) is the study of Greek words aitia = cause and logos = word/speech) is used in philosophy, physics and biology in reference to the causes of various phenomena. It is generally the study of why things occur, or even the reasons behind the way that things act... aetiology of Alzheimer's disease let to the development and introduction of Memantine is an NMDA receptor antagonist used in the treatment of Alzheimers disease. It differs from traditional agents used in Alzheimers disease by acting on glutamatergic neurotransmission, rather than cholinergic. It is marketed by Lundbeck under the trade names Ebixa, Axura, and Namenda. Pharmacology There is some evidence... memantine. Memantine is a novel The NMDA receptor (NMDAR) is an ionotropic receptor for glutamate (NMDA is a name of its selective specific agonist). NMDARs play a critical role in synaptic plasticity mechanisms and thus are necessary for several types of learning and memory. Structure Each NMDA receptor contains four or five subunits, the exact... NMDA receptor Categories: Biology stubs | Biochemistry | Pharmacology ... antagonist, and has been shown to be moderately clinically efficacious. (Areosa et al., 2004)

Vaccine

There are ongoing tests of an Alzheimer's disease vaccine. This was based on the idea that if you could train the immune system to recognize and attack beta-amyloid placque, the immune system might reverse deposition of amyloid and thus stop the disease. Initial results in animals were promising. However, when the first vaccines were used in humans, brain inflammation occurred in a small fraction of participants, and the trials were stopped. Participants in the halted trials continued to be followed, and some showed lingering benefits in the form of slower progression of the disease. Recent studies in mice continue to show promise that an approach may be found to avoid the inflammation issue. 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.

Genetic and population effects

Various gene An allele is any one of a number of alternative forms of the same gene occupying a given locus (position) on a chromosome. An example is the gene for blossom color in many species of flower _ a single gene controls the color of the petals, but there may be... alleles have been associated with Alzheimer's disease, most notably the apolipoprotein E (ApoE) gene. ApoE normally functions to regulate Cholesterol is a steroid lipid, found in the cell membranes of all body tissues, and transported in the blood plasma of all animals. Most cholesterol is not dietary in origin, it is synthesized internally. It is present in higher concentrations in tissues which either produce more or have more densely... cholesterol Santorio Santorio (1561-1636) in his steelyard balance, from Ars de statica medecina, first published 1614 Metabolism (from μεταβολισμος(metavallo), the Greek word for change), in the most general sense, is the ingestion and breakdown of complex compounds, coupled... 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. For this reason, money spent informing the public of available effective prevention methods may yield disproportionate benefits.

History

The symptoms of the disease as a distinct nosologic entity were first identified by Emil Kraepelin (February 15, 1856- October 7, 1926) was a psychiatrist who attempted to create a synthesis of the hundreds of mental disorders classified by the 19th century, grouping diseases together based on classification of common patterns of symptoms, rather than by simple similarity of major symptoms in the manner... Emil Kraepelin, and the characteristic neuropathology was first observed by Alois Alzheimer Alois Alzheimer (June 14, 1864 - December 19, 1915), a German neurologist, was a colleague of Emil Kraepelin who first identified the symptoms of what is now known as Alzheimers Disease. He observed the disease in 1906. He was born in a small town called Marktbreit, Bavaria, where his... Alois Alzheimer in 1906 was a common year starting on Monday (see link for calendar). Events January 8 - Landslide in Haverstraw, New York kills 20 January 31 - Earthquake in Ecuador (8.6 in Richter scale) February 11 - Pope Pius X publishes the encyclical Vehementer nos. February 15 - Representatives of the Labour Representation Committee... 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

• Enid Blyton (August 11, 1897 - November 28, 1968) was a British childrens author. She is noted particularly for numerous series of books, based on recurring characters and designed for different age groups. Her prolific output involved mainly escapist childrens fantasy, often but not always involving the supernatural. Her... Enid Blyton
• Carroll A. Campbell, Jr.
• Hon Alfred Deakin Alfred Deakin (August 3, 1856 - October 7, 1919), intellectual leader of the movement for Australian federation and second Prime Minister of Australia, was born in Melbourne, Victoria, the son of English immigrants. He was educated at Melbourne Grammar School and graduated in law from the University of... Alfred Deakin (probable, died in 1919)
• James Montgomery Doohan (born March 3, 1920) is a Canadian actor and linguist best known for his portrayal of Scotty in the television and movie series Star Trek. Doohan was born in Vancouver, British Columbia; his family later moved to Sarnia, Ontario where he attended high school at SCITS, Sarnia... James Doohan
• Ralph Waldo Emerson Ralph Waldo Emerson (May 25, 1803–April 27, 1882) was a famous American essayist and one of Americas most influential thinkers and writers. Life Emerson was born in Boston, Massachusetts, to a Unitarian minister and would later become a Unitarian minister himself. Emerson eventually, however... Ralph Waldo Emerson
• Barry Goldwater Barry Morris Goldwater (January 1, 1909 _ May 29, 1998) was a United States politician and a founding figure in the modern conservative movement in the USA. Goldwater personified the shift in balance in American culture from the Northeast to the West. A five_term United States Senator from... Barry Goldwater
• Rita Hayworth Rita Hayworth (real name Margarita Carmen Cansino) (October 17, 1918 - May 14, 1987) was a famous American film star during the 1940s who was sometimes called The Love Goddess or The Great American Love Goddess. First attracting attention of film producers as part of the dance team The... Rita Hayworth
• The artists rendering of a bare_headed Charlton Heston as Moses was bulked up to modern physique standards when the DVD was released Charlton Heston (born October 4, American film actor noted for heroic roles. Later in his life, Heston became famous as a conservative activist, especially as president of... Charlton Heston
• Beatrice Lillie (29 May 1894-20 January 1989) was the outstanding comedic actress of her time. Beatrice Lillie She was born Beatrice Gladys Lillie (not, as is sometimes claimed, as Constance Sylvia Munsfird) in Toronto, Ontario in Canada. Beatrice Lillie began performing in Toronto and other Ontario towns as part... Beatrice Lillie
• Queen Juliana Juliana Louise Emma Marie Wilhelmina, Duchess of Mecklenburg-Schwerin, (April 30, 1909 - March 20, 2004) of the House of Orange-Nassau was Queen of the Netherlands from her mothers abdication in 1948 to her own abdication in 1980 and Queen Mother (with the title of Princess) from... Juliana of the Netherlands
• Burgess Meredith (November 16, 1909 _ September 9, 1997) was an American actor, perhaps best known for playing the Penguin on the television series Batman. The Penguins trademark quacking laugh was actually Merediths attempt to cover up coughing fits, as his part required him to smoke, something he... Burgess Meredith
• Iris Murdoch Dame Jean Iris Murdoch (July 15, 1919 - February 8, 1999) was an Anglo-Irish novelist and philosopher, famed for her series of novels that combine rich characterization and compelling plotlines usually involving ethical or sexual themes. Life and work Murdoch was born in 1919 in Dublin and studied... Iris Murdoch
• Joseph-Maurice Ravel (March 7, 1875 – December 28, 1937) was a French composer and pianist, best known for his orchestral work, Boléro, and his famous 1922 orchestral arrangement of Modest Mussorgskys Pictures at an Exhibition. He himself had described Boléro as a piece for orchestra without... Maurice Ravel
• Order: 40th President Vice President: George H.W. Bush Term of office: January 20, 1981 – January 20, 1989 Preceded by: Jimmy Carter Succeeded by: George H.W. Bush Date of birth: February 6, 1911 Place of birth: Tampico, Illinois Date... Ronald Reagan
• Walker Smith Jr. (May 3, 1921 - April 12, 1989), better known in the boxing world as Sugar Ray Robinson, was a boxer who was a native of Detroit, Michigan. Robinson is the holder of many boxing records, including the one for the most times being a champion in a division... Sugar Ray Robinson
• Dame Margaret Rutherford (May 11, 1892 – May 22, 1972) was a British character actress who first came to prominence following World War II in the film adaptations of Noel Cowards Blithe Spirit, and Oscar Wildes The Importance of Being Earnest. Born in London, she made her stage... Margaret Rutherford
• Robert Sargent Shriver, Jr. (born November 9, 1915) is an American politician, known for his association with the Kennedy family, most notably John F. Kennedy and Robert F. Kennedy, and as the main organiser and first director of the Peace Corps. He received his bachelors degree from Yale University... Robert Sargent Shriver
• Charles A. Steen, Uranium King Charles A. Steen (b. 1919), was a student of geology who made a fortune after discovering a rich uranium deposit in Utah, sparking the Uranium Rush of the early 1950s. Steen was born in Caddo, Texas and attended high school in Houston. He went on... Charles Steen
• Cyrus Roberts Vance (March 27, 1917–January 12, 2002), was the United States Secretary of State under President Jimmy Carter from 1977 to 1980. He approached foreign policy with an emphasis on negotiation over conflict and a special interest in arms reduction. In April of 1980, Vance resigned in... Cyrus Vance
• Elwyn Brooks White (July 11, 1899–October 1, 1985) was an American essayist, author, and noted prose stylist. He is most famous today for a writers style guide, The Elements of Style, and for three childrens books generally considered to be classics of the field. White was born... E.B. White
• James Harold Wilson, Baron Wilson of Rievaulx, KG, OBE, PC (March 11, 1916 - May 24, 1995) was one of the more successful Labour Prime Ministers of the United Kingdom and a 1960s icon. Wilson is regarded by many as probably one of the more intellectual politicians of the century. Birth... Harold Wilson

See also

• Professor Chi Ming Yang, of Nankai University (pinyin: Nankai Daxue; simplified: 南开大学 traditional: 南開大學), located in Tianjin, is one of the leading universities in China. It is also the alma mater of the late Premier Zhou Enlai. Founded in 1919 by the renowned patriotic educationist Zhang Boling (1876-1951... Nankai University in Tianjin (Chinese: 天津; pinyin: tiān jīn; Postal System Pinyin: Tientsin) is a harbour municipality in China on the Hai He River (from Beijing) and Bohai Gulf of the Yellow Sea (Pacific Ocean). The placename literally means the Heavenly Ford. Tianjin is one of four independent... Tianjin, The Great Wall of China, stretching over 6,700 km, was erected beginning in the 3rd century BC to guard the north from raids by men on horses. China  listen? ( Traditional: 中國; Simplified: 中国; pinyin: ; Wade-Giles: Chung-kuo) is a nation located chiefly in continental East... China, has discovered that prion protein associated with Creutzfeldt-Jakob Disease (CJD) is a lethal brain disorder characterized by memory loss, personality changes, hallucinations, speech impairment, jerky movements, changes in gait, rigid posture, and seizures due to a rapid loss of neural cells caused by transmissible proteins called prions. The disease is correctly diagnosed in anywhere from one... vCJD and the amyloid precursor protein associated with early stage Alzheimer's have very similar In chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. In biochemistry, this shorter and more general term is frequently used to refer to alpha amino acids: those amino acids in which the amino and carboxylate functionalities are attached to the same carbon... amino acid sequences.[7] (http://news.bbc.co.uk/1/hi/health/892819.stm)

• Familial Alzheimers disease is an uncommon form of Alzheimers disease that comes on earlier in life (usually between 30 and 60 years of age) and is inherited in an autosomal dominant fashion. While it only accounts for 5% or less of total Alzheimers disease, it has presented... Familial Alzheimer disease

Reference

• Areosa SA, McShane R, Sherriff F. Memantine for dementia. The Cochrane Collaboration developed in response to Archie Cochranes call for systematic, up-to-date reviews of all relevant randomized clinical trials of health care. Cochranes suggestion that the methods used to prepare and maintain reviews of controlled trials in pregnancy and childbirth should be applied more widely... Cochrane Database Syst Rev 2004(4);CD003154.pub2. PMID 15495043
• Courtney C, Farrell D, Gray R, Hills R, Lynch L, Sellwood E, Edwards S, Hardyman W, Raftery J, Crome P, Lendon C, Shaw H, Bentham P; AD2000 Collaborative Group. Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial. The Lancet is a British medical journal, published weekly by the Lancet Publishing Group. It takes its name from the surgical instrument called a lancet. The present editor-in-chief is Richard Horton. There are several specialized editions of The Lancet, called The Lancet Neurology, The Lancet Oncology and The... Lancet 2004;363:2105-15. PMID 15220031.

External links

• Alzheimer's Disease: Molecular Mechanisms (http://www.benbest.com/lifeext/Alzheimer.html)
• Journal of Alzheimer's Disease (http://www.j-alz.com)
• Mental Health Matters: Alzheimer's Disease (http://www.mental-health-matters.com/disorders/dis_details.php?disID=5)
• Psych Forums: Alzheimer's Forum (http://www.psychforums.com/forums/viewforum.php?f=155)
• Molecule that could stop protein clumping preceding Alzheimer (http://news.bbc.co.uk/2/hi/health/3959381.stm)
• Alzheimer's Association (http://alz.org)