Drc. Mclachlan et al., DESFERRIOXAMINE AND ALZHEIMERS-DISEASE - VIDEO HOME BEHAVIOR ASSESSMENT OF CLINICAL COURSE AND MEASURES OF BRAIN ALUMINUM, Therapeutic drug monitoring, 15(6), 1993, pp. 602-607
Drug trials designed to modify the progression of Alzheimer's disease
(AD) have required the development of mental state and behavior evalua
tion instruments that are sensitive to cognitive decline and measure s
kills useful in everyday living. We describe a videotaped home behavio
r (VHB) assessment instrument with high construct validity and reliabi
lity and a strong relationship to criterion references. The VHB was em
ployed to test the hypothesis that aluminum is an important pathogenic
factor in AD. The trivalent chelating agent desferrioxamine (DFO), 12
5 mg i.m. twice daily five days per week, was used in a randomized sin
gle-blind, oral lecithin, placebo-controlled clinical trial in 48 pati
ents with AD. Analysis showed that the treatment and no-treatment grou
ps were closely matched at entry into the trial but that the rate of d
ecline, 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 concent
rations to near control concentrations. Aluminum ion-specific chelatio
n may be a useful palliative treatment for AD, and further clinical tr
ials are indicated.