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23/01/2015 10:01 # 1
Nghiem_huyen
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Alzheimer’s Disease: Managing Unique Pharmacotherapy Need


Background Alzheimer’s disease (AD) is a form of dementia accounting for approximately 60% to 80% of dementia cases. Although it may affect patients in different ways, it is most commonly associated with a gradual worsening of the ability to remember new information. It is a progressive disorder with treatments that, at best, result in modest improvement. Although it is not a normal part of the aging process, advanced age is the greatest risk factor. As the US population ages, life expectancy increases, and the baby boom generation reaches retirement age, the number of cases of AD is expected to increase from 4.7 million in 2010 to 8.4 million by 2030.1 Types of Dementia Although AD is the most common type of dementia, there are other types, and each type is associated with distinct symptom patterns and brain abnormalities. Recent studies show that mixed dementia is more common than previously thought. The most common types and their characteristics are presented in Table 1.1 Treatment There are no treatments that stop the progression of AD. Primary goals of treatment should focus on improving the quality of life and maximizing functional performance by enhancing cognition, mood, and behavior. Nonpharmacologic treatment options should be utilized and include activities such as scheduled toileting to help with urinary incontinence, and graded assistance with activities of daily living to promote increased independence. Music, walking, light exercise, family presence, and pet therapy may help patients with problem behaviors.2 Pharmacologic therapy should first focus on optimizing treatment of comorbid conditions and avoiding medications that may impair cognitive function, such as anticholinergic medications, benzodiazepines, and sedatives.3 There are several FDA-approved medications for treatment of AD. These include the cholinesterase inhibitors donepezil, galantamine, and rivastigmine, and the N-methyl-D-aspartate receptor antagonist (NMDA) memantine.2 It is believed that in AD, accumulation of beta-amyloid plaques outside the neurons and accumulation of an abnormal form of the protein tau inside neurons harms information transfer at the synapses in neural tissues. This accumulation harms neuron-to-neuron communication, blocks transport of nutrients to the neuron, and contributes to cell death.1 This process leads to a loss of cholinergic neurons in the brain and a decreased level of acetylcholine. Acetylcholinesterase inhibitors increase acetylcholine levels in the synapses and boost cholinergic neurotransmission in the forebrain regions to compensate for the loss of functioning brain cells.4 They are approved for the treatment of mild or moderate AD, with donepezil also approved for severe AD. Only 10% to 25% of patients taking acetylcholinesterase inhibitors show modest global improvement, but many have less rapid cognitive decline. Side effects include nausea, vomiting, diarrhea, dyspepsia, anorexia, weight loss, leg cramps, bradycardia, syncope, insomnia, and agitation. Adverse effects increase with higher dosages.1-3 The NMDA memantine is thought to be neuroprotective by preventing excessive glutamate activation of NMDA receptors. It has been shown to have modest efficacy in moderate to severe AD as monotherapy or when combined with donepezil. Side effects include confusion, dizziness, constipation, and headache.2-3,5 - See more at: http://www.pharmacytimes.com/publications/health-system-edition/2015/January2015/Alzheimers-Disease-Managing-Unique-Pharmacotherapy-Needs#sthash.f6dvtO5n.dpuf



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