The financial and social splendors...

The financial and social splendors of Alzheimer's disease are staggering. In the United States, the disease accounts for about $100 billion for year in medical and custodial costs with the average patient requiring an expenditure of about $27000 by year for medical and nursing care. In addition, 80 percent of caregivers report stres and about 50 percent report depression. (12) This article reviews the pathophysiology of Alzheimer's disease, evidence for the efficacy of various pharmacologic treatments, and guidelines for the use of put drugs into therapy in patients with this devastating disease.

Pathophysiology

couple microscopic changes occur in the brain in Alzheimer's disease: senile plaques disentangle between neurons, and neurofibrillary tangles unravel within neurons. These changes are cogitation to be intricately related to the cause, disentanglement and course of the disease.

Researchers have speculated that inflammation around plaques subverts neighboring neurons. Plaques, which are compos of b-amyloid polypeptides, pretend to form as a accrue of disorders in processing b-amyloid and its precursor protein. A combination of genetic predisposition and environmental influences is probably responsible. (3) individual of these influences may be subclinical ischemia, because patients with high vital fluid pressure and elevated cholesterol plains tend to have an increased risk for Alzheimer's disease. (4) Neurofibrillary tangles are made up partly of a protein called tau, which links together to form filaments. The density of these filaments within neuron in the brain is directly related to the severity of dementia. It is unclear on what account tangles form, but different alleles of a gene are known to create forms of tau that are more likely to tangle. (3) It is also unclear whether tangles are linked to plaque formation. The ultimate power of the tangles, however, is compromise of microtubular function, with eventual destruction of the neuron Involvement of cholinergic neuron causes flushs of acetylcholine within synapses to decline. horizontals of acetylcholinesterase also drop, perhaps to compensate for the los of acetylcholine. Activity of another cholinesterase enzyme (butyrylcholinesterase) increases, and a significant portion of acetylcholine is metabolized by dint of this enzyme as the disease progresse Eventually, the neuron is destroyed

Pharmacologic Therapy

While no medicine has been shown to completely guard neurons, agents that inhibit the degradation of acetylcholine within the synapse are the mainstay of treatment for Alzheimer's disease. Cholinesterase/acetylcholinesterase inhibitors are the solely agents approved by the U sustenance and Drug Administration for the treatment of Alzheimer's disease. Other unsalable articles have been studied, but their use remains controversial.

ACETYLCHOLINESTERASE INHIBITORS

The cholinesterase inhibitor tacrine (Cognex) is used rarely because of potential liver toxicity and the ne for haunt laboratory monitoring. The acetylcholinesterase inhibitors donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl) have been prov effective in clinical trials. Table 1 (5-7) compares the pharmacologic characteristics of the three acetylcholinesterase inhibitors and provides dosing and expense information.

All three put drugs intos have a low incidence of serious reactions, if it were not that they commonly have cholinergic side general intents such as nausea, anorexia, vomiting, and diarrhea. Tolerance to these side tenors often develops. However, if therapy with an acetylcholinesterase inhibitor is interrupted for more than several days, the medicine should be restarted at the lowest dosage and retitrated, because of renewed susceptibility to side effects

Instruments that measure cognition, behavior, and functional ability have shown that acetylcholinesterase inhibitors are beneficial in patients with Alzheimer's disease. While these instruments are discussed in greater detail elsewhere, (8) the principally commonly used scales are summarized in Table 2 (9-15)

Although clinical trials have shown that treatment with acetylcholinesterase inhibitors delays nursing domestic circle placement and improves cognition and functional ability, these benefits may not apply to all patients with Alzheimer's disease. For example, patients might be exclud from a subject of attention if they have significant coexisting illnesses with symptoms that could be confused with remedy side effects. Consequently, the close attention population might consist of patients who are more likely to rejoin to the drug.

Nonetheless, it is safe to bring to an end that patients who tolerate and be agreeable to to acetylcholinesterase inhibitors will experience pure cognitive improvements. In fact, deterioration of cognition will be delayed by dint of one year in about 20 percent of treated patients (as measured by the agency of a seven-point improvement on the Alzheimer's Disease Assessment Scale, Cognitive Section). (5616) [Reference 16--Evidence on a level A, randomized controlled trial] Table 3 (5-716-23) summarizes evidence for the benefits of acetylcholinesterase inhibitors.