title: Synergistic effect of apolipoprotein E epsilon4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease.
abstract: OBJECTIVE
  To evaluate the synergistic effects of the apolipoprotein E (APOE) epsilon4 and butyrylcholinesterase K-variant (BCHE-K) alleles on progression to Alzheimer's disease (AD) in individuals with mild cognitive impairment (MCI).
  
  
  METHODS
  This was a post-hoc exploratory analysis from a 3-4-year, randomized, placebo-controlled study of rivastigmine in participants with MCI (InDDEx study). Participants who consented to genetic testing were included in the current analyses. The incidence of progression to AD, cognitive decline and changes in MRI brain volumes were investigated in participants from the placebo arm of the InDDEx study.
  
  
  RESULTS
  Of the 1018 participants in the overall study, 464 were successfully genotyped for both APOE and butyrylcholinesterase. Of these, 68 (14.7%) carried > or =1 APOE epsilon4 and > or =1 BCHE-K allele. The presence of APOE epsilon4 was associated with a significantly higher incidence of progression to AD whereas the presence of BCHE-K had no independent effect on progression. A synergistic effect of the combined presence of APOE epsilon4 and BCHE-K on the time to clinical diagnosis of AD and on MRI brain volumes was seen. Progression to AD and hippocampal volumetric loss was greatest in participants who carried both APOE epsilon4 and BCHE-K alleles and lowest in BCHE-K carriers without the APOE epsilon4 allele.
  
  
  CONCLUSIONS
  In MCI, the risk of cognitive decline, hippocampal volumetric loss and progression to AD seems to be the greatest in individuals who carry at least one copy of both the BCHE-K and APOE epsilon4 alleles.
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936-1080, USA. roger.lane@novartis.com
authors.forename: Roger
authors.initials: R
authors.lastname: Lane
authors.forename: Howard H
authors.initials: HH
authors.lastname: Feldman
authors.forename: Joanne
authors.initials: J
authors.lastname: Meyer
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: He
authors.forename: Steven H
authors.initials: SH
authors.lastname: Ferris
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
authors.forename: Taher
authors.initials: T
authors.lastname: Darreh-Shori
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Tuula
authors.initials: T
authors.lastname: Pirttilä
authors.forename: Martin R
authors.initials: MR
authors.lastname: Farlow
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Sfikas
authors.forename: Clive
authors.initials: C
authors.lastname: Ballard
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Greig
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics*; D002091:Butyrylcholinesterase / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests
chemical_list: D053327:Apolipoprotein E4; D002091:Butyrylcholinesterase