Desferrioxamine and Alzheimer's disease: video home behavior assessment of clinical course and measures of brain aluminum

Abstract

Drug trials designed to modify the progression of Alzheimer's disease (AD) have required the development of mental state and behavior evaluation instruments that are sensitive to cognitive decline and measure skills useful in everyday living. We describe a videotaped home behavior (VHB) assessment instrument with high construct validity and reliability and a strong relationship to criterion references. The VHB was employed to test the hypothesis that aluminum is an important pathogenic factor in AD. The trivalent chelating agent desferrioxamine (DFO), 125 mg i.m. twice daily five days per week, was used in a randomized single-blind, oral lecithin, placebo-controlled clinical trial in 48 patients with AD. Analysis showed that the treatment and no-treatment groups were closely matched at entry into the trial but that the rate of decline, as measured by the VHB over 2 years of observation, was twice as rapid in the no-treatment group compared with the DFO-treated group. Furthermore, trace-metal analysis of autopsied brain confirmed that extended treatment with DFO lowered neocortical brain aluminum concentrations to near control concentrations. Aluminum ion-specific chelation may be a useful palliative treatment for AD, and further clinical trials are indicated.