title: Serum albumin level interferes with the effect of donepezil in Alzheimer's disease.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our preliminary data suggest that serum albumin level should be monitored to evaluate the clinical efficacy of ChEIs therapy.
authors.affiliation: Department of Neurology, University of Brescia, Brescia, Italy. lrozzini@iol.it
authors.forename: Luca
authors.initials: L
authors.lastname: Rozzini
authors.forename: Barbara Vicini
authors.initials: BV
authors.lastname: Chilovi
authors.forename: Erik
authors.initials: E
authors.lastname: Bertoletti
authors.forename: Diego
authors.initials: D
authors.lastname: Ghianda
authors.forename: Marta
authors.initials: M
authors.lastname: Conti
authors.forename: Marco
authors.initials: M
authors.lastname: Trabucchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics*; D003071:Cognition / Q000187:drug effects*; D000077265:Donepezil; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007189:Indans / Q000493:pharmacokinetics*; D008297:Male; D010880:Piperidines / Q000493:pharmacokinetics*; D012709:Serum Albumin / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D012709:Serum Albumin; D000077265:Donepezil