Association of Butyrylcholinesterase-K Allele and Apolipoprotein E ɛ4 Allele with Cognitive Decline in Dementia with Lewy Bodies and Alzheimer's Disease

J Alzheimers Dis. 2016;50(2):567-76. doi: 10.3233/JAD-150750.


Background: A common polymorphism of the butyrylcholinesterase gene, the K-variant (BCHE-K) is associated with reduced butyrylcholinesterase (BuChE) activity. Insufficient studies exist regarding the frequency and role of BCHE-K in dementias.

Objective: To determine the association of BCHE-K and APOEɛ4 with diagnosis and rate of cognitive decline in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) patients.

Methods: Genomic DNA from 368 subjects (108 AD, 174 DLB, and 86 controls) from two routine clinical cohort studies in Norway; DemVest and TrønderBrain, were genotyped for BCHE-K and APOEɛ4. The mild dementia DemVest subjects received annual Mini-Mental State Examination assessments for five years.

Results: BCHE-K frequency was lower in DLB (33.9% ; p < 0.01) than in control subjects (51.2%), and was numerically lower in AD as well (38.9% ; p = 0.11). More rapid cognitive decline was associated with the APOEɛ4 genotype, but not with the BCHE-K genotype. In an exploratory analysis of patients who completed all five follow-up visits, there was greater cognitive decline in BCHE-K carriers in the presence of the APOEɛ4 allele than in the absence of these polymorphisms.

Conclusion: BCHE-K is associated with a reduced risk for AD and DLB whereas APOEɛ4 is associated with more rapid cognitive decline. The greater cognitive decline in individuals with both APOEɛ4 and BCHE-K alleles require prospective confirmation in well-controlled trials.

Keywords: Apolipoprotein E genotype; Mini-Mental State Examination; butyrylcholinesterase-K; cognition; dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / psychology
  • Apolipoprotein E4 / genetics*
  • Butyrylcholinesterase / genetics*
  • Cognition / physiology*
  • Disease Progression
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Lewy Body Disease / genetics*
  • Lewy Body Disease / psychology
  • Male
  • Neuropsychological Tests


  • Apolipoprotein E4
  • Butyrylcholinesterase