Effect of rivastigmine or memantine add-on therapy is affected by butyrylcholinesterase genotype in patients with probable Alzheimer's disease.
BACKGROUND
The K variant of butyrylcholinesterase (BCHE-K) exhibits a reduced acetylcholine-hydrolyzing capacity; so the clinical response to rivastigmine may differ in Alzheimer's disease (AD) patients with the BCHE-K gene.


OBJECTIVE
To investigate the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine transdermal patch therapy in AD patients based on the BCHE-K gene.


METHODS
A total of 146 probable AD patients consented to genetic testing for butyrylcholinesterase and underwent the final efficacy evaluations. Responders were defined as patients with an equal or better score on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) at 16 weeks compared to their baseline score.


RESULTS
BCHE-K carriers showed a lower responder rate on the ADAS-cog than non-carriers (38.2 vs. 61.7%, p = 0.02), and this trend was evident in AD patients with apolipoprotein E ε 4 (35 vs. 60.7%, p = 0.001). The presence of the BCHE-K allele predicted a worse response on the ADAS-cog (odds ratio 0.35, 95% confidence interval 0.14-0.87), after adjusting for demographic and baseline cognitive and functional variables.


CONCLUSIONS
The BCHE-K genotype may be related to a poor cognitive response to rivastigmine patch or memantine add-on therapy, especially in the presence of apolipoprotein E ε 4.
Department of Neurology, Myongji Hospital, Goyang, Republic of Korea.
Hyun Jeong
HJ
Han
Jay C
JC
Kwon
Jung Eun
JE
Kim
Shin Gyeom
SG
Kim
Jong-Moo
JM
Park
Kyung Won
KW
Park
Key Chung
KC
Park
Kee Hyung
KH
Park
So Young
SY
Moon
Sang Won
SW
Seo
Seong Hye
SH
Choi
Soo-Jin
SJ
Cho
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D002091:Butyrylcholinesterase / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008559:Memantine / Q000008:administration & dosage*; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D016017:Odds Ratio; D000068836:Rivastigmine / Q000008:administration & dosage*; D057968:Transdermal Patch
D053327:Apolipoprotein E4; D018696:Neuroprotective Agents; D002091:Butyrylcholinesterase; D000068836:Rivastigmine; D008559:Memantine