IC-P3-209: Serum albumin level interferes with the effect of donepezil in Alzheimer's disease

The most successful therapeutic approaches of Alzheimer's Disease have involved acetylcholinesterase inhibitors (ChEIs). Given the different response rates to ChEIs therapy, it is important to identify the pharmacokinetic and pharmacodinamic mechanisms possibly interfering 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 characterized by different serum albumin levels, a condition modifying drug distribution. A total of 110 Alzheimer patients treated with donepezil were analyzed in an outpatient clinic between January 2003 and January 2005. At study entry, participants underwent a multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. Every concomitant illness and treatment was recorded. Patients were grouped in categories (patients with low, medium and high albumin levels). The total sample of patients showed a cognitive improvement from baseline of the ADAS Cog score at three months (ADAS Cog mean change -1,4±5,4; p=0,01), a cognitive stabilization at nine (ADAS Cog mean change 0,03±6,7; p=NS) and a worsening not statistically significant at fifteen months (ADAS Cog mean change 0,9±7,3; p=NS). The study demonstrates that lower serum albumin levels are associated with a greater response of donepezil. In fact, cognition, evaluated with ADAS Cog mean change from baseline, improved during the first 15 months of treatment in lower serum albumin level group, while worsened in higher serum albumin level groups. Data suggest the importance of taking in consideration various clinical and biological parameters to predict the clinical efficacy of ChEIs therapy.