Article Text

Download PDFPDF
Rate of progression of cognitive decline in Alzheimer’s disease: effect of butyrylcholinesterase K gene variation
  1. C Holmes1,
  2. C Ballard2,
  3. D Lehmann3,
  4. A David Smith3,
  5. H Beaumont3,
  6. I N Day1,
  7. M Nadeem Khan4,
  8. S Lovestone4,
  9. M McCulley1,
  10. C M Morris2,
  11. D G Munoz5,
  12. K O’Brien2,
  13. C Russ4,
  14. T Del Ser5,
  15. D Warden3
  1. 1University of Southampton, Southampton, UK
  2. 2Newcastle General Hospital, Newcastle-upon-Tyne, UK
  3. 3OPTIMA, Department of Pharmacology, University of Oxford and Radcliffe Infirmary, Oxford, UK
  4. 4The Institute of Psychiatry, London, UK
  5. 5Department of Neurology, Madrid, Spain and University of Western Ontario, Canada
  1. Correspondence to:
 Dr C Holmes
 University of Southampton, Clinical Neurosciences Research Division, Memory Assessment and Research Centre, Moorgreen Hospital, Botley Road, Southampton;


Objective: To determine whether individuals with Alzheimer’s disease (AD) and the K variant allele of butyrylcholinesterase have a slower rate of cognitive decline than those without the K variant allele of butyrylcholinesterase.

Method: The cognitive status of 339 community based subjects with AD was assessed with the Mini Mental State Examination at baseline and yearly over a three year follow up period. The rates of cognitive decline of subjects with and without the K variant allele were compared.

Result: Presence of the K allele was associated with a slower average rate of cognitive decline in subjects with severe AD.

Conclusions: This finding is consistent with the suggestion that the K variant of butyrylcholinesterase has an important role in disease progression in AD, and this may have implications for treatment.

  • AD, Alzheimer’s disease
  • ApoE, apolipoprotein E
  • CDCR, Camberwell Dementia Case Register
  • MMSE, Mini Mental State Examination
  • OPTIMA, Oxford Project to Investigate Memory and Ageing
  • Alzheimer’s disease
  • butyrylcholinesterase
  • cognitive decline
  • genetics

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • This study was funded in part by Novartis Pharmaceuticals which has a special interest in the role of butyrylcholinesterase in the progression of Alzheimer’s disease; Bristol Myers Squibb; the Norman Collisson Foundation; and by the Wellcome Trust.

  • Competing interests: S Lovestone has research collaborations and has received speaker’s fees and educational grants from a variety of companies that manufacture cholinesterase inhibitors that may or may not have some butyrylcholinesterase inhibitor activity also. C Holmes has acted in a consultancy role and has obtained funds for research, and C Ballard has acted in a consultancy role, received fees for speaking and has obtained funds for research, from Novartis, manufacturer of rivastigmine which markets a drug that has inhibitory properties on butyrylcholinesterase.