Miranda Luís F J R, Gomes Karina B, Silveira Josianne N, Pianetti Gerson A, Byrro Ricardo M D, Peles Patrícia R H, Pereira Fernando H, Santos Thiago R, Assini Arthur G, Ribeiro Valéria V, Tito Pedro A L, Matoso Rafael O, Lima Thiago O L, Moraes Edgar N, Caramelli Paulo
Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil.
Faculdade de Farmácia da Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brasil.
J Alzheimers Dis. 2015;45(2):609-20. doi: 10.3233/JAD-142148.
Naturalistic studies evaluate individuals in their usual way of living, presenting more "real-life" data regarding patients and their diseases.
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).
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.
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.
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.
自然主义研究以个体的日常生活方式对其进行评估,呈现出更多关于患者及其疾病的“真实生活”数据。
研究在阿尔茨海默病(AD)和AD合并脑血管病(CVD)中,可能预测对胆碱酯酶抑制剂(ChEI)治疗有良好反应的人口统计学、临床和遗传因素。
共有129例患者被诊断为AD或AD合并CVD,且患有轻度至中度痴呆。经过12个月的治疗后,97例患者完成了研究。在使用ChEI(多奈哌齐、卡巴拉汀或加兰他敏)治疗的基线、3个月、6个月和12个月后对他们进行评估。测定了所有参与者的载脂蛋白E(APOE)基因型和细胞色素P450 2D6(CYP2D6)基因多态性。在每次就诊时,我们使用了认知、功能、情绪和行为量表。我们根据简易精神状态检查表(MMSE)的得分对患者进行分类。良好反应者被定义为在12个月时MMSE得分≥2分的患者。
良好临床反应率为27.8%。在纵向分析中,轻度AD且在3个月时也是良好反应者的患者在12个月时被视为良好反应者。ChEI剂量、APOE和CYP2D6基因多态性与临床反应模式之间无相关性。
与以往研究相比,本研究中观察到较高的良好反应率。药物遗传学方面似乎对反应没有影响。