Clin Psychopharmacol Neurosci.  2015 Aug;13(2):168-173. 10.9758/cpn.2015.13.2.168.

The Effect of Choline Acetyltransferase Genotype on Donepezil Treatment Response in Patients with Alzheimer's Disease

  • 1Department of Psychiatry, Kangwon National University School of Medicine, Chuncheon, Korea.
  • 2Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Korea.
  • 3Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea.
  • 4Department of Neuropsychiatry, Kyunggi Provincial Hospital for the Elderly, Yongin, Korea.
  • 5Department of Psychiatry, Chungnam National University Hospital, Daejeon, Korea.
  • 6Department of Psychiatry, Konkuk University Chungju Hospital, Chungju, Korea.
  • 7Department of Psychiatry, Gyeongsang National University Hospital, Jinju, Korea.
  • 8Department of Neuropsychiatry, Konkuk University Hospital, Seoul, Korea.
  • 9Department of Neuropsychiatry, Jeju National University Hospital, Jeju, Korea.
  • 10Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
  • 11Department of Psychiatry, Jeonju City Welfare Hospital for the Elderly, Jeonju, Korea.
  • 12Department of Psychiatry, Kyungbook National University Hospital, Daegu, Korea.
  • 13Department of Psychiatry, Haeundae Paik Hospital, Busan, Korea.
  • 14Department of Psychiatry, Chuncheon Sacred Hospital, Chuncheon, Korea.
  • 15Department of Psychiatry, Uijeongbu St. Mary's Hospital, Uijeongbu, Korea.
  • 16Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, Korea.
  • 17Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea.


We examined the difference in responses to donepezil between carriers and non-carriers of the A allele at the +4 position of the choline acetyltransferase (ChAT) gene in Koreans.
Patients who met the criteria for probable Alzheimer's disease (AD) (n=199) were recruited. Among these, 145 completed the 12-week follow-up evaluation and 135 completed the 26-week scheduled course. Differences and changes in the Korean version of the mini-mental state examination (MMSE-KC) score, Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-K[N]) wordlist subtest score (WSS), CERAD-K(N) total score (TS), and the Korean version of geriatric depression scale (GDS-K) score between baseline and 12 weeks or 26 weeks were assessed by the Student's t-test.
At 12 weeks, the changes in the MMSE-KC score, CERAD-K(N) WSS, and CERAD-K(N) TS from baseline were not significant between ChAT A allele carriers and non-carriers; however, at 26 weeks, these changes were significantly larger in ChAT A allele carriers than in non-carriers (p=0.02 for MMSE-KC and p=0.03 for CERAD-K(N) WSS respectively).
Our findings in this study suggested that presence of the A allele at the +4 position of ChAT might positively influence the treatment effect of donepezil in the early stages of AD in Koreans.


Choline acetyltransferase; Single nucleotide polymorphism; Alzheimer disease; Donepezil
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