细胞色素 P4502D6 和载脂蛋白 E 基因型是否与多奈哌齐治疗患者的长期认知和功能变化相关？

Are cytochrome P4502D6 and apolipoprotein E genotypes associated with long-term cognitive and functional changes in patients treated with donepezil?

机构信息

Department of Medicine (DIMED), Geriatrics Division, University of Padua, Padua, Italy.

National Research Council, Neuroscience Institute, Padua, Italy.

出版信息

Psychogeriatrics. 2020 Sep;20(5):578-584. doi: 10.1111/psyg.12547. Epub 2020 Apr 1.

DOI:10.1111/psyg.12547

PMID:32237281

Abstract

AIM

We investigated the associations of the single-nucleotide polymorphism rs1080985 of cytochrome P4502D6 (CYP2D6) and the apolipoprotein E (APOE) genotypes with cognitive and functional changes in patients treated with donepezil.

METHODS

Sixty-five outpatients with Alzheimer's disease or mixed dementia being treated with donepezil were assessed at baseline and over 27 months. Changes in cognitive status, assessed with the Mini-Mental State Examination, and in functional status, assessed by the Activities of Daily Living Scale and the Instrumental Activities of Daily Living Scale, were evaluated as a function of CYP2D6 and APOE genotypes by using linear mixed models. Multiplicative interactions between the CYP2D6 and APOE genotypes and time were investigated.

RESULTS

Individuals with the mutated CYP2D6 exhibited a slower decline in total Mini-Mental State Examination scores, orientation, registration, and functional status than those with the wild type. A significant interaction between CYP2D6, APOE, and time was found for changes in the Activities of Daily Living Scale; among the ε4 carriers, those with the mutated CYP2D6 exhibited a slower decline on the Activities of Daily Living Scale than those with the wild type.

CONCLUSION

The CYP2D6 and APOE genotypes may modulate the effectiveness of donepezil on cognitive and functional status.

摘要

目的

我们研究了细胞色素 P4502D6（CYP2D6）的单核苷酸多态性 rs1080985 和载脂蛋白 E（APOE）基因型与接受多奈哌齐治疗的患者认知和功能变化的相关性。

方法

65 例接受多奈哌齐治疗的阿尔茨海默病或混合性痴呆患者在基线和 27 个月内接受评估。采用 Mini-Mental State Examination 评估认知状态变化，采用日常生活活动量表和工具性日常生活活动量表评估功能状态变化，采用线性混合模型评估 CYP2D6 和 APOE 基因型的作用。研究了 CYP2D6 和 APOE 基因型与时间之间的相乘交互作用。

结果

与野生型相比，突变型 CYP2D6 个体的总 Mini-Mental State Examination 评分、定向、登记和功能状态下降速度较慢。发现 Activities of Daily Living Scale 的变化存在 CYP2D6、APOE 和时间的显著交互作用；在 ε4 携带者中，突变型 CYP2D6 个体的 Activities of Daily Living Scale 下降速度比野生型慢。