Alzheimer's disease (AD), also called Alzheimer disease or simply Alzheimer's, is the most common cause of dementia, afflicting 24 million people worldwide. Alzheimer's is a degenerative and terminal disease for which there is currently no known cure. In its most common form, it occurs in people over 65 years old although a less-prevalent early-onset form also exists. The disease can begin many years before it is eventually diagnosed. In its early stages, short-term memory loss is the most common symptom, often initially thought to be caused by aging or stress by the sufferer. Later symptoms include confusion, anger, mood swings, language breakdown, long-term memory loss, and the general withdrawal of the sufferer as his or her senses decline. Gradually the sufferer loses minor, and then major bodily functions, until death occurs. Although the symptoms are common, each individual experiences the symptoms in unique ways. The duration of the disease is estimated as being between 5 and 20 years.
Causes:
Most cases of Alzheimer's disease do not exhibit familial inheritance. At least 80% of sporadic AD cases involve genetic risk factors. Inheritance of the ε4 allele of the apolipoprotein E (ApoE) gene is regarded as a risk factor for development of up to 50% of late-onset sporadic Alzheimer's. The presence of this gene allele along with infection by Herpes Simplex Virus Type 1 (HSV-1) further increases the risk of Alzheimer's disease. Several viral-host interactions are postulated, most relating to HSV-1’s targeting of Alzheimer’s susceptibility genes. Genetic experts agree that there are other risk and protective factor genes that influence the development of late onset Alzheimer's disease. Over 400 genes have been tested for association with late-onset sporadic AD.
Nearly 200 different mutations in the presenilin-1 or presenilin-2 genes have been documented in over 500 families. Mutations of presenilin 1 (PS1) lead to the most aggressive form of familial Alzheimer's disease. Over twenty different mutations in the amyloid precursor protein (APP) gene on chromosome 21 can also cause early onset of the disease.
Treatment:
There is an observed reduction in activity of the cholinergic neurons in the disease. Acetylcholinesterase 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). AChE-inhibitors seem to modestly moderate symptoms but do not alter the course of the underlying dementing process. They have also been critized for their reduced clinical utility, cost and side effects. Examples currently marketed include donepezil (Brand name Aricept), galantamine (Razadyne) and rivastigmine (Marketed as Exelon and Exelon Patch). Donepezil and galantamine are taken orally. Rivastigmine has oral forms and a once-daily transdermal patch.
Involvement of glutamatergic neuronal excitotoxicity in Alzheimer's disease led to the development and introduction of memantine (Brand names Akatinol, Axura, Ebixa/Abixa, Memox and Namenda). Memantine is a novel NMDA receptor antagonist, and has been shown to be moderately clinically efficacious.
Causes:
Most cases of Alzheimer's disease do not exhibit familial inheritance. At least 80% of sporadic AD cases involve genetic risk factors. Inheritance of the ε4 allele of the apolipoprotein E (ApoE) gene is regarded as a risk factor for development of up to 50% of late-onset sporadic Alzheimer's. The presence of this gene allele along with infection by Herpes Simplex Virus Type 1 (HSV-1) further increases the risk of Alzheimer's disease. Several viral-host interactions are postulated, most relating to HSV-1’s targeting of Alzheimer’s susceptibility genes. Genetic experts agree that there are other risk and protective factor genes that influence the development of late onset Alzheimer's disease. Over 400 genes have been tested for association with late-onset sporadic AD.
Nearly 200 different mutations in the presenilin-1 or presenilin-2 genes have been documented in over 500 families. Mutations of presenilin 1 (PS1) lead to the most aggressive form of familial Alzheimer's disease. Over twenty different mutations in the amyloid precursor protein (APP) gene on chromosome 21 can also cause early onset of the disease.
Treatment:
There is an observed reduction in activity of the cholinergic neurons in the disease. Acetylcholinesterase 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). AChE-inhibitors seem to modestly moderate symptoms but do not alter the course of the underlying dementing process. They have also been critized for their reduced clinical utility, cost and side effects. Examples currently marketed include donepezil (Brand name Aricept), galantamine (Razadyne) and rivastigmine (Marketed as Exelon and Exelon Patch). Donepezil and galantamine are taken orally. Rivastigmine has oral forms and a once-daily transdermal patch.
Involvement of glutamatergic neuronal excitotoxicity in Alzheimer's disease led to the development and introduction of memantine (Brand names Akatinol, Axura, Ebixa/Abixa, Memox and Namenda). Memantine is a novel NMDA receptor antagonist, and has been shown to be moderately clinically efficacious.
No comments:
Post a Comment