Effect of rivastigmine or memantine add-on therapy is affected by butyrylcholinesterase genotype in patients with probable Alzheimer's disease.

Abstract

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.

CONCLUSION: 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.