title: Effect of the apolipoprotein E epsilon4 allele on the efficacy and tolerability of galantamine in the treatment of Alzheimer's disease.
abstract: OBJECTIVE
  To investigate the effect of the apolipoprotein E (ApoE) epsilon4 allele on the efficacy and tolerability of galantamine treatment.
  
  
  METHODS
  A total of 202 patients with mild to moderate Alzheimer's disease participated in a 16-week, prospective, multi-center, randomized, double-blind galantamine trial in a Korean population. Patients were assessed at baseline and after 4, 8 and 16 weeks of randomized treatment using the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog/11), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia Scale (DAD), the Behavioural Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and adverse events. ApoE genotypes were determined for all subjects.
  
  
  RESULTS
  Of the 202 subjects, 115 carried at least one ApoE epsilon4 allele and 87 did not. In both ApoE epsilon4 carriers and ApoE epsilon4 noncarriers, significant improvements were detected relative to baseline on ADAS-cog/11, CIBIC-plus, DAD and BEHAVE-AD. ApoE epsilon4 noncarriers showed better improvement in mean total BEHAVE-AD score and mean psychosis (delusions and hallucinations) subscale score than ApoE epsilon4 carriers. The incidence of weight loss was significantly higher in ApoE epsilon4 carriers (n = 11; 9.6%) than in ApoE epsilon4 noncarriers (n = 1; 1.2%) during this 16-week study, even though 92% of patients who complained of weight loss completed this 16-week trial successfully.
  
  
  CONCLUSIONS
  ApoE epsilon4 genotype does not affect galantamine-related improvements in cognition, global rating, function and behavior. Longer prospective studies with larger patient populations are required to confirm these new findings.
authors.affiliation: Division of Neuroscience and Psychological Medicine, Imperial College, School of Medicine, and West London Mental Health NHS, London, UK. suhgh@chol.com
authors.forename: Guk-Hee
authors.initials: GH
authors.lastname: Suh
authors.forename: Hee Yeon
authors.initials: HY
authors.lastname: Jung
authors.forename: Chang Uk
authors.initials: CU
authors.lastname: Lee
authors.forename: Byoung Hoon
authors.initials: BH
authors.lastname: Oh
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Lee
authors.forename: NamJin
authors.initials: N
authors.lastname: Lee
authors.forename: JaeHyun
authors.initials: J
authors.lastname: Kim
authors.forename: Baik Seok
authors.initials: BS
authors.lastname: Kee
authors.forename: Daekwan
authors.initials: D
authors.lastname: Ko
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Young-Su
authors.initials: YS
authors.lastname: Ju
authors.forename: InJa
authors.initials: I
authors.lastname: Hong
authors.forename: Sungku
authors.initials: S
authors.lastname: Choi
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D003702:Delusions / Q000188:drug therapy / Q000235:genetics; D004311:Double-Blind Method; D005702:Galantamine / Q000009:adverse effects / Q000627:therapeutic use*; D006212:Hallucinations / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D018697:Nootropic Agents; D005702:Galantamine