载脂蛋白 E ε4 修饰了可能的抗胆碱能药物对新发痴呆的影响：上海老龄化研究。

Apolipoprotein E ε4 Modifies the Effect of Possible Anticholinergic Drugs on Incident Dementia: The Shanghai Aging Study.

机构信息

Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.

Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

J Am Med Dir Assoc. 2023 Apr;24(4):526-532. doi: 10.1016/j.jamda.2023.01.018. Epub 2023 Feb 24.

DOI:10.1016/j.jamda.2023.01.018

PMID:36842452

Abstract

OBJECTIVES

To validate the hypothesis that apolipoprotein E (APOE) ε4 modifies the effect of possible anticholinergic drugs (PACDs) on incident dementia among older adults.

DESIGN

A population-based prospective study.

SETTING AND PARTICIPANTS

Dementia-free older adults in an urban community in Shanghai, China.

METHODS

At baseline, PACDs were defined according to the Anticholinergic Cognitive Burden Scale. Standard daily dose (SDD) of PACDs was calculated. A battery of neuropsychological tests was used to assess cognition and the consensus diagnosis was conducted for incident dementia and Alzheimer's disease (AD). Multivariate Cox regression models were used to examine the association between PACD use and the risk of dementia and AD in APOE ε4 carriers and noncarriers.

RESULTS

We followed 1406 dementia-free participants for a median of 5.3 years and defined 117 incident dementia cases, among which 89 were AD. Only in APOE ε4 carriers was PACD use associated with incident dementia [hazard ratio (HR) 5.71; 95% CI 2.04-15.94] and AD (HR 5.73; 95% CI 1.77-18.54); SDD was positively associated with incident dementia (HR 2.42; 95% CI 1.32-4.44) and AD (HR 2.16; 95% CI 1.06-4.41).

CONCLUSIONS AND IMPLICATIONS

Using PACDs requires judicious consideration for the potential risk of dementia and AD in older adults carrying APOE ε4.

摘要

目的

验证载脂蛋白 E（APOE）ε4 修饰可能的抗胆碱能药物（PACDs）对老年人群中痴呆发生的影响这一假说。

设计

基于人群的前瞻性研究。

地点和参与者

中国上海城市社区中无痴呆的老年人。

方法

在基线时，根据抗胆碱能认知负担量表定义 PACDs。计算 PACDs 的标准日剂量（SDD）。使用一系列神经心理学测试来评估认知，并且对痴呆和阿尔茨海默病（AD）的新发病例进行共识诊断。多变量 Cox 回归模型用于检验 APOE ε4 携带者和非携带者中 PACDs 使用与痴呆和 AD 风险之间的关联。

结果

我们对 1406 名无痴呆的参与者进行了中位数为 5.3 年的随访，并定义了 117 例新发痴呆病例，其中 89 例为 AD。仅在 APOE ε4 携带者中，PACDs 使用与痴呆（风险比[HR]5.71；95%置信区间[CI]2.04-15.94）和 AD（HR 5.73；95% CI 1.77-18.54）的发生有关；SDD 与痴呆（HR 2.42；95% CI 1.32-4.44）和 AD（HR 2.16；95% CI 1.06-4.41）的发生呈正相关。