Alternatives in the treatment of memory loss in patients with Alzheimer's disease.
The pathophysiology, symptomatology, and treatment of memory loss in patients with Alzheimer's disease are described. Alzheimer's disease is characterized by cerebral cortical atrophy, neuronal loss, neurofibrillary tangles, and neuritic plaques. The primary neuropharmacologic defect involves reduced activity of the enzyme choline acetyltransferase, causing reduced synthesis of acetylcholine (ACh). Other neurotransmitters known to be compromised in patients with Alzheimer's disease include norepinephrine, serotonin, dopamine, and somatostatin. Initially components of short-term memory and immediate recall are lost. Eventually, memory loss is so severe that patients lose the ability to care for themselves. A definite diagnosis of Alzheimer's disease can be made only at autopsy. Three pharmacologic approaches to enhancing cholinergic function include increasing ACh production by increasing the availability of ACh precursors (lecithin, choline); inhibiting ACh degradation by inhibiting acetylcholinesterase (physostigmine, tacrine hydrochloride); and directly stimulating cholinergic receptors by using cholinomimetic agents (arecoline, RS-86). However, results of studies involving these agents are conflicting: no consistent benefit has been shown in patients with Alzheimer's disease. Although therapy with tacrine hydrochloride has been beneficial in some patients, it has not been effective in all cases and has the potential to cause serious adverse effects. Despite the research in patients with Alzheimer's disease, no agent has yet been found that produces consistent improvement in the memory loss associated with this disease.
Volger
B W
BW
Drug Information and Investigational Drug Services, University of Michigan Hospitals, Ann Arbor 48109-0008.
D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D015337:Multicenter Studies as Topic; D010713:Phosphatidylcholines / Q000627:therapeutic use*; D010830:Physostigmine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013619:Tacrine / Q000627:therapeutic use*
D010713:Phosphatidylcholines; D013619:Tacrine; D010830:Physostigmine