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 I 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 I 4. i 2014 S. Karger AG, Basel

Lane RM, Potkin SG, Enz A: Targeting acetylcholinesterase and butyrylcholinesterase in dementia. Int J Neuropsychopharmacol 2006;9:101-124.
Bartels CF, James K, La Du BN: DNA mutations associated with the human butyrylcholinesterase J-variant. Am J Hum Genet 1992;50:1104-1114.
Podoly E, Shalev DE, Shenhar-Tsarfaty S, Bennett ER, Ben Assayag E, Wilgus H, Livnah O, Soreq H: The butyrylcholinesterase K variant confers structurally derived risks for Alzheimer pathology. J Biol Chem 2009;284:17170-17179.
Alvarez-Arcaya A, Combarros O, Llorca J, Sanchez-Guerra M, Berciano J, Fernandez-Viadero C, Pena N: The butyrylcholinesterase K variant is a protective factor for sporadic Alzheimer's disease in women. Acta Neurol Scand 2000;102:350-353.
Lane RM, He Y: Butyrylcholinesterase genotype and gender influence Alzheimer's disease phenotype. Alzheimers Dement 2013;9:e17-e73.
Darreh-Shori T, Siawesh M, Mousavi M, Andreasen N, Nordberg A: Apolipoprotein epsilon4 modulates phenotype of butyrylcholinesterase in CSF of patients with Alzheimer's disease. J Alzheimers Dis 2012;28:443-458.
O'Brien KK, Saxby BK, Ballard CG, Grace J, Harrington F, Ford GA, O'Brien JT, Swan AG, Fairbairn AF, Wesnes K, del Ser T, Edwardson JA, Morris CM, McKeith IG: Regulation of attention and response to therapy in dementia by butyrylcholinesterase. Pharmacogenetics 2003;13:231-239.
Blesa R, Bullock R, He Y, Bergman H, Gambina G, Meyer J, Rapatz G, Nagel J, Lane R: Effect of butyrylcholinesterase genotype on the response to rivastigmine or donepezil in younger patients with Alzheimer's disease. Pharmacogenet Genomics 2006;16:771-774.
Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I; Memantine Study Group: Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004;291:317-324.
Farrimond LE, Roberts E, McShane R: Memantine and cholinesterase inhibitor combination therapy for Alzheimer's disease: a systematic review. BMJ Open 2012;2:e000917.
Choi SH, Park KW, Na DL, Han HJ, Kim EJ, Shim YS, Lee JH; Expect Study Group: Tolerability and efficacy of memantine add-on therapy to rivastigmine transdermal patches in mild to moderate Alzheimer's disease: a multicenter, randomized, open-label, parallel-group study. Curr Med Res Opin 2011;27:1375-1383.
Han HJ, Kim BC, Lee JY, Ryu SH, Na HR, Yoon SJ, Park HY, Shin JH, Cho SJ, Yi HA, Choi MS, Heo JH, Park KW, Kim KK, Choi SH: Response to rivastigmine transdermal patch or memantine plus rivastigmine patch is affected by apolipoprotein E genotype in Alzheimer patients. Dement Geriatr Cogn Disord 2012;34:167-173.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939-944.
Folstein MF, Folstein SE, McHugh PR: ‘Mini-mental state'. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.
Rosen WG, Mohs RC, Davis KL: A new rating scale for Alzheimer's disease. Am J Psychiatry 1984;141:1356-1364.
Dubois B, Slachevsky A, Litvan I, Pillon B: The FAB: a Frontal Assessment Battery at bedside. Neurology 2000;55:1621-1626.
Kang SJ, Choi SH, Lee BH, Jeong Y, Hahn DS, Han IW, Cummings JL, Na DL: Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI). J Geriatr Psychiatry Neurol 2004;17:32-35.
Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, Ferris S: An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997;11:S33-S39.
Morris JC: The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993;43:2412-2414.
Ballard C, Morris C, Kalaria R, McKeith I, Perry R, Perry E: The K variant of the butyrylcholinesterase gene is associated with reduced phosphorylation of tau in dementia patients. Dement Geriatr Cogn Disord 2005;19:357-360.
Kennedy RE, Cutter GR, Schneider LS: Effect of APOE genotype status on targeted clinical trials outcomes and efficiency in dementia and mild cognitive impairment resulting from Alzheimer's disease. Alzheimers Dement 2014;10:349-359.
Darreh-Shori T, Hosseini SM, Nordberg A: Pharmacodynamics of cholinesterase inhibitors suggests add-on therapy with a low-dose carbamylating inhibitor in patients on long-term treatment with rapidly reversible inhibitors. J Alzheimers Dis 2014;39:423-440.
Nakamura Y, Imai Y, Shigeta M, Graf A, Shirahase T, Kim H, Fujii A, Mori J, Homma A: A 24-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety and tolerability of the rivastigmine patch in Japanese patients with Alzheimer's disease. Dement Geriatr Cogn Dis Extra 2011;1:163-179.
Grossberg GT, Manes F, Allegri RF, Gutierrez-Robledo LM, Gloger S, Xie L, Jia XD, Pejovic V, Miller ML, Perhach JL, Graham SM: The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer's disease taking cholinesterase inhibitors. CNS Drugs 2013;27:469-478.
Ballard CG: Advances in the treatment of Alzheimer's disease: benefits of dual cholinesterase inhibition. Eur Neurol 2002;47:64-70.
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