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What is Alzheimer's disease?

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Introduction

Alzheimer's disease What is Alzheimer's disease? Alzheimer's disease (AD) is the most common causative brain disease first characterised by Alois Alzheimer in 1907, his findings were the changes in the brain tissue of a women who had died of an unusual mental illness, when a post mortem commenced, abnormal clumps known as senile or neuritic plaques and tangled bundles of fibres known as neurofibrillary tangles (NFTs) were found. These plaques and tangles in the brain are considered as neuropathological hallmarks of AD. AD is classified under Dementia, Delirium, and Amnestic disorders (Crimson & Eggert 1994). Dementias are neuropyschiatric disorders defined by widespread symptoms of memory loss, deficits in cognition, and behaviour. Dementias result from the underlying disease, and are not part of normal ageing. Delirium differs from dementia in that it develops over a short period of time, and involves an acute change in the level of consciousness in addition to decline in cognition. The severity, prognosis, and treatment of dementia are dependent entirely on the underlying cause, and accurate diagnosis. AD is becoming increasingly prevalent, and is the most common cause of dementia. The disease usually begins after the age of 65, and risk of AD goes up with age. While younger people also may have AD, it is much less common. It is important to note, however, that AD is not normal part of ageing. AD affects more than 3% of the 65-74 year old age group and more then 45% of those over the age of 85 years (Hier, 1997). ...read more.

Middle

It is possible to make predictive testing that indicates which individual will eventually develop the inherited AD. Another genetic linkage susceptibility to late-onset AD is influenced by apolipoprotein E genotype. Apoliprotein E (APO E) functions as a carrier for cholesterol in the bloodstream and central nervous system and also involved in cellular repair and regeneration. In the brain, APO E is produced by astrocytes and is important in distributing cholesterol for repair of neuronal membranes and myelin. Therefore the production is increased following damage of neuronal tissue (Mirra, 1997). The gene, which produces APO E, is situated on chromosome 19 in a region previously linked/associated with late-onset AD. There are three main alleles of APO E, known as APO E2, E3, and E4. Humans inherit one copy of the APO E gene from each parent. APO E3 is the most common type (90% of individuals have at least one copy), with E2 and E4 occurring less frequently (Behl C. 1999). Inheritance of the E4 allele increases the risk for developing AD compared to those with E2 and E3 (Evans, 2001). Graph may be added pg 1068 APO E binds to the BAP deposits located in neuritic plaques and cerebral vessels in the brains of AD patients and is also associated with NFT's. However the exact role of APO E in the genesis of AD is unclear a protein known as low density lipoprotein (LRP), a receptor for APO E which usually transports cholesterol, and processing release of APP. LRP is found in neuritic plaques (Rockville, 1996). ...read more.

Conclusion

Results of these studies showed statistically significant benefit in both of the primary outcome measures (cognitive function and global clinical impressions), which was somewhat greater at 10 mg/day. Donepezil has been reported to be safer and more tolerable (especially in terms of gastrointestinal distress) than tacrine. Donepezil was approved by the Food and Drug Administration (FDA) in November 1996 for a number of reasons: Its efficacy is generally equivalent to that of tacrine, it is not associated with hepatotoxicity or elevated transaminase levels, and it is thought to have fewer cholinergic side effects than tacrine. The ease of its once-daily dosing may result in improved patient compliance. It also has reduced potential for drug-drug interactions and may be taken with food. Because of donepezil's improved tolerability and because therapeutic doses are achieved quickly, rather than taking months, substantially more patients are expected to experience benefit with donepezil than with tacrine. Further information about donepezil also suggests that, as with some other cholinergic agents, improvement gained with early treatment is sustained with ongoing therapy (17). Studies are under way to assess donepezil's effectiveness over the long term as well as in patients with more severe dementia or comorbid medical conditions; results should help illuminate its usefulness in a broader patient population. Table 3. Adverse Events Associated With Donepezil* Adverse Event� Placebo (n = 355) (%) Donepezil (n = 747) (%) Nausea 6 11 Diarrhea 5 10 Insomnia 6 9 Vomiting 3 5 Muscle cramp 2 6 Fatigue 3 5 * Eisai Inc.: Aricept(r) (donepezil hydrochloride tablets) [package insert]. Teaneck, NJ 1998 �Occurring in at least 5% of patients and more often than in patients receiving placebo. ...read more.

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