title: Progression from mild cognitive impairment to Alzheimer's disease: effects of sex, butyrylcholinesterase genotype, and rivastigmine treatment.
abstract: OBJECTIVE
  Evaluate the effect of sex and butyrylcholinesterase (BuChE) genotype on the incidence of Alzheimer's disease (AD), cognitive and functional decline, brain volume changes, and response to rivastigmine treatment in individuals with mild cognitive impairment (MCI).
  
  
  METHODS
  This retrospective exploratory analysis from a 3-4 year, randomized, placebo-controlled study of rivastigmine in MCI patients included participants who consented to pharmacogenetic testing.
  
  
  RESULTS
  Of a total of 1018 patients, 490 [253 (52%) female] were successfully genotyped for BuChE. In patients receiving placebo, the BuChE wt/wt genotype was associated with a statistically significant higher incidence of progression to AD and functional decline in women, compared with men with the BuChE wt/wt genotype. In patients with a BuChE-K allele receiving placebo, incidence of progression to AD and rate of functional decline were not significantly different by sex; however, cognitive decline was significantly faster in men. Statistically significant benefits of rivastigmine treatment on incident AD, functional decline, ventricular volume expansion, whole-brain atrophy, and white matter loss were evident in female BuChE wt/wt.
  
  
  CONCLUSIONS
  Sex and BuChE genotype seem to differentially influence the type of decline in MCI patients, with more rapid progression of cognitive decline in male BuChE-K, and more incident AD and functional decline in female BuChE wt/wt. Cognitive decline in male BuChE-K and functional decline and incident AD in female BuChE wt/wt were significantly attenuated by rivastigmine. Rivastigmine treatment also significantly reduced ventricular expansion, whole-brain atrophy rate, and white matter loss in female BuChE wt/wt, suggesting a possible disease-modifying effect.
authors.affiliation: Alzheimer's Disease Center, Center of Excellence on Brain Aging, NYU Langone Medical Center, Orangeburg, New York, USA. steven.ferris@nyumc.org
authors.forename: Steven
authors.initials: S
authors.lastname: Ferris
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Taher
authors.initials: T
authors.lastname: Darreh-Shori
authors.forename: Roger
authors.initials: R
authors.lastname: Lane
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000235:genetics*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003071:Cognition; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D010597:Pharmacogenetics / Q000379:methods; D048448:Phenylcarbamates / Q000494:pharmacology*; D010919:Placebos; D012189:Retrospective Studies; D000068836:Rivastigmine; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D010919:Placebos; D002091:Butyrylcholinesterase; D000068836:Rivastigmine