Predictive Factors of Clinical Response to Cholinesterase Inhibitors in Mild and Moderate Alzheimer's Disease and Mixed Dementia: A One-Year Naturalistic Study

Article type: Research Article

Authors: Miranda, Luís F.J.R.^a | Gomes, Karina B.^b | Silveira, Josianne N.^b | Pianetti, Gerson A.^b | Byrro, Ricardo M.D.^b | Peles, Patrícia R.H.^c | Pereira, Fernando H.^a | Santos, Thiago R.^d | Assini, Arthur G.^b | Ribeiro, Valéria V.^b | Tito, Pedro A.L.^e | Matoso, Rafael O.^a | Lima, Thiago O.L.^a | Moraes, Edgar N.^{a; f} | Caramelli, Paulo^{a; c; *}

Affiliations: [a] Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil | [b] Faculdade de Farmácia da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil | [c] Serviço de Neurologia do Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil | [d] Instituto de Ciências Exatas da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil | [e] Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil | [f] Serviço de Geriatria do Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil

Correspondence: [*] Correspondence to: Paulo Caramelli, MD, PhD, Departamento de Clínica Médica, Faculdade de Medicina da UFMG, Av. Prof. Alfredo Balena, 190 - Room 246, 30130-100, Belo Horizonte (MG), Brazil. Tel./Fax: +55 31 3409 9746; E-mail: [email protected].

Abstract: Background:Naturalistic studies evaluate individuals in their usual way of living, presenting more “real-life” data regarding patients and their diseases. Objective:To investigate demographic, clinical, and genetic factors that could be predictive of good response to cholinesterase inhibitors (ChEI) treatment in Alzheimer’s disease (AD) and AD + cerebrovascular disease (CVD). Patients and Methods:A total of 129 patients were diagnosed with AD or AD + CVD and with mild-to-moderate dementia. After a 12-month treatment, 97 patients completed the study. They were evaluated at baseline and after three, six, and 12 months of ChEI (donepezil or rivastigmine or galantamine) use. APOE genotype and CYP2D6 polymorphisms were determined for all of the participants. In each visit, we used cognitive, functional, mood, and behavior scales. We classified patients according to their scores in the Mini-Mental State Examination (MMSE). Good responders were defined as those scoring ≥2 in the MMSE at 12 months. Results:The rate of good clinical response was 27.8%. In a longitudinal analysis, the patients with mild AD and also good responders at three months were considered to be good responders at 12 months. There was no correlation between ChEI dose, APOE and CYP2D6 polymorphisms, and the pattern of clinical response. Conclusion:A higher rate of good response was observed in this study compared to that in previous investigations. The pharmacogenetic aspects do not seem to have an influence in the response.

Keywords: Alzheimer's disease, APOE and CYP2D6 polymorphisms, cholinesterase inhibitors, predictive factors, response

DOI: 10.3233/JAD-142148

Journal: Journal of Alzheimer's Disease, vol. 45, no. 2, pp. 609-620, 2015