Pharmacological Approach to Demented Patients

Woo, Haingwon

Abstract

Of all patients with dementia, 50-60% have dmentia of Alzheimer's type, and vascular dementia represents 17-29% of all cases. Other common causes of dementia include drugs, toxins, intracranial masses, anoxia, infections, neurodegenerative disorders, metabolic disorders, and chronic infalmmatory disorders. Treatment approach to demented patients may account for drug therapy in Al-zheimer's disease, because about 10-23% of patients have coexisting vascular dementia and dementia of Alzheimer's type. Dementia other than Alzheimer's disease also show various degrees of impairment of cognitive and non-cognitive function such as depression, psychosis and other behavioral problems, therefore pharmacological treatment for specific symptoms should be provided and therapy should be directed toward treating the underiying cuases as well. Alzheimer's disease (AD) is the most important of all the degenerative disease with progressive impairment of cognitive function and neuropsychiatric disturbance. Neuropathologic investigations have shown that cholinergic neuronal loss is seen in the nucleus basalis of Meynert, and choline acetyltransferase and acctylcholine esterase are decreased in the cerebral cortex. This hypothesis led to attempts to correct the dificiency with cholinomimetic agents and proved to be effective in some patients. However, there have been no pharmacologic agent proved to be suce-ssful. The most recent of these is the reversible acetyl cholinesterase inhibitor with long half life and high affirnity to CNS, Aricept (donepezil), which produces great improvement in cognitive function in clinical trials in Europe and US without compromized hepatotoxicity. The other pathophysiology of AD includes wide range of neurotransmitter imbalances and cortical atrophy, so that combined treatment apporach such as choinergic/serotonergic drug and cholinergic/somatostatinergic drug should be considered. As a preventive approach, neurotrophic factor, which may delay degenerative process of cholinergic neuron, is clinically valuable when administrated directly into ventricles. In many cases, amyloid deposits are seen as the distinctive neuropathology of AD, and the evidence that amyloid peptide genes found to be on chromosome 21 will lead the gene therapy for this diseases. As the disease advances, various degrees of neuropsychiatric distrubance become so marked that may be helped by treatment of associated depression, anxiety, disruptive behavior, and psychotic symtoms with appropriate psychotropic medication. However, these drugs may make patients confused, requiring reduced ro withdrawal of the medication. therefore, a careful attempt should be made, since demands on enviromental apporach and behavioral therapy are high.