ABSTRACT
The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer's disease (AD) and AD with cerebrovascular disease who took donepezil (10âmg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥-1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score. The study results indicated the good response pattern was influenced by the concentration of donepezil, but not by APOE and CYP2D6 polymorphisms.
Subject(s)
Apolipoproteins E/genetics , Cholinesterase Inhibitors/blood , Cholinesterase Inhibitors/therapeutic use , Cytochrome P-450 CYP2D6/genetics , Dementia , Indans/blood , Indans/therapeutic use , Piperidines/blood , Piperidines/therapeutic use , Polymorphism, Single Nucleotide/genetics , Chromatography, High Pressure Liquid , Dementia/blood , Dementia/drug therapy , Dementia/genetics , Donepezil , Female , Follow-Up Studies , Humans , Male , Mental Status and Dementia Tests , Neuropsychological Tests , Time FactorsABSTRACT
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.
