Serum albumin level interferes with the effect of Donepezil in Alzheimer’s disease

Abstract

The most successful therapeutic approaches to Alzheimer's disease (AD) have involved acetylcholinesterase inhibitors (ChEIs). In view of the different response rates to ChEIs therapy, it is important to identify the pharmacokinetic and pharmacodynamic mechanisms which may interfere with this effect. The aim of the study is to evaluate the efficacy on cognition of donepezil, a cholinesterase inhibitor, in a sample of mild to moderate AD patients with various serum albumin levels, a condition modifying drug distribution. Ninety-eight Alzheimer patients treated with donepezil were analyzed in an outpatient clinic between January 2003 and January 2005. At study entry, participants underwent multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. All concomitant illnesses and treatments were recorded. Patients were grouped in three categories (with low, medium and high albumin levels). The total sample of patients showed cognitive improvement from baseline of the ADAS Cog score at three months (ADAS Cog mean change -1.4+5.4; p=0.01), cognitive stabilization at nine (ADAS Cog mean change 0.03+6.7; p=ns), and not statistically significant worsening at fifteen months (ADAS Cog mean change 0.9+7.3; p=ns). The low serum albumin level group was associated with a greater response to donepezil. In fact, cognition, evaluated by the ADAS Cog mean change from baseline, improved during the first 15 months of treatment in the low serum albumin level group, but worsened in the two higher groups. Our preliminary data suggest that serum albumin level should be monitored to evaluate the clinical efficacy of ChEIs therapy.