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社区居住的轻度至中度阿尔茨海默病老年人的镇静负荷:与不良事件、谵妄和跌倒的纵向关系。

Sedative Load in Community-Dwelling Older Adults with Mild-Moderate Alzheimer's Disease: Longitudinal Relationships with Adverse Events, Delirium and Falls.

机构信息

Department of Age-Related Healthcare, Tallaght University Hospital, Dublin, Ireland.

Department of Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin 2, Dublin, Ireland.

出版信息

Drugs Aging. 2020 Nov;37(11):829-837. doi: 10.1007/s40266-020-00800-y. Epub 2020 Sep 14.

Abstract

BACKGROUND

Older adults are frequently prescribed medications with sedative effects, which are associated with numerous adverse consequences. However, the prevalence and longitudinal associations of sedative medication use in community-dwelling older adults with mild-moderate Alzheimer's disease (AD) has not been explored to date.

OBJECTIVES

Our objective was to assess the prevalence of sedative medication use in community-dwelling older adults with mild-moderate AD and examine the longitudinal association between sedative medication use and adverse events (AEs).

METHODS

The association between baseline sedative load (SL) and AEs, unscheduled healthcare utilisation, delirium and falls was assessed in older adults with mild-moderate AD over 18 months using secondary analysis of NILVAD trial data (collected from 2014 to 2016). Baseline medication use was assessed, and the SL model was applied to each participant's medication individually. The SL model classifies medications into one of four categories: (1) primary sedatives, (2) medications with a sedating component or prominent side effect, (3) medications with sedation as a potential adverse reaction and (4) all other medications with no known sedative side effects. Medications in group 1 were assigned an SL score of 2, those in group 2 were assigned an SL score of 1, and those in categories 3 and 4 an SL score of 0. SL scores for each medication participants were taking were summed and the total SL calculated as an arithmetic sum of individual medications score. A total SL score ≥ 3 was classed as high. Statistical analysis was conducted using Poisson regression and mixed-effects linear regression, with adjustment for important clinical covariates. We also assessed the impact of SL on dementia progression and cognitive decline.

RESULTS

Over half (55.7% [284/510]) of those with mild-moderate AD (age 72.8 ± 8.3 years, 61.9% female) were prescribed a regular medication with sedation as a primary effect or prominent side effect, with 22.2% (113/510) having a high SL (≥ 3). The most common medications contributing to SL were antidepressants, antipsychotics, anxiolytics and hypnotics. Over 18 months, increasing baseline SL was associated with incident AEs (incidence rate ratio [IRR] 1.15; 95% confidence interval [CI] 1.11-1.19; p < 0.001), serious AEs (IRR 1.23; 95% CI 1.11-1.36; p < 0.001) and unscheduled general practitioner visits (IRR 1.23; 95% CI 1.13-1.34; p < 0.001). Further, increasing SL was associated with a greater likelihood of incident delirium (IRR 1.30; 95% CI 1.11-1.53; p < 0.001) and falls (IRR 1.20; 95% CI 1.03-1.42; p = 0.02). Associations persisted after robust covariate adjustment. SL was not associated with accelerated cognitive decline or AD progression.

CONCLUSIONS

In the current study, over half of older adults with mild-moderate AD were prescribed at least one drug with a sedative effect, and a significant minority had a high SL. Increasing baseline SL was associated with a greater likelihood of incident AEs, delirium and falls, highlighting the need for optimal prescribing in this potentially vulnerable cohort.

摘要

背景

老年人经常被开具有镇静作用的药物,这些药物与许多不良后果有关。然而,迄今为止,尚未探讨社区居住的轻度至中度阿尔茨海默病(AD)老年人中镇静药物的使用频率和纵向关联。

目的

我们的目的是评估社区居住的轻度至中度 AD 老年人中镇静药物的使用频率,并检查镇静药物使用与不良事件(AE)之间的纵向关联。

方法

使用 NILVAD 试验(于 2014 年至 2016 年收集)的数据进行二次分析,评估了 18 个月内轻度至中度 AD 老年人的基线镇静负荷(SL)与 AE、非计划性医疗保健利用、谵妄和跌倒之间的关联。评估了基线药物使用情况,并将 SL 模型应用于每位参与者的药物。SL 模型将药物分为四类之一:(1)主要镇静剂,(2)具有镇静成分或突出副作用的药物,(3)具有镇静作用的潜在不良反应的药物,以及(4)具有已知镇静副作用的所有其他药物。组 1 中的药物被分配 SL 得分为 2,组 2 中的药物被分配 SL 得分为 1,而组 3 和 4 中的药物被分配 SL 得分为 0。参与者服用的每种药物的 SL 分数相加,总 SL 计算为个体药物分数的算术和。总 SL 评分≥3 被归类为高。使用泊松回归和混合效应线性回归进行统计分析,并对重要的临床协变量进行调整。我们还评估了 SL 对痴呆进展和认知下降的影响。

结果

超过一半(55.7% [284/510])的轻度至中度 AD(年龄 72.8 ± 8.3 岁,61.9%为女性)被开具有镇静作用或突出副作用的常规药物,其中 22.2%(113/510)的 SL 较高(≥3)。导致 SL 较高的最常见药物是抗抑郁药、抗精神病药、抗焦虑药和催眠药。在 18 个月期间,基线 SL 的增加与新发生的 AE(发病率比 [IRR] 1.15;95%置信区间 [CI] 1.11-1.19;p<0.001)、严重 AE(IRR 1.23;95% CI 1.11-1.36;p<0.001)和非计划性全科医生就诊(IRR 1.23;95% CI 1.13-1.34;p<0.001)相关。此外,SL 的增加与发生谵妄(IRR 1.30;95% CI 1.11-1.53;p<0.001)和跌倒(IRR 1.20;95% CI 1.03-1.42;p=0.02)的可能性更大相关。在进行了稳健的协变量调整后,这些关联仍然存在。SL 与加速认知下降或 AD 进展无关。

结论

在目前的研究中,超过一半的轻度至中度 AD 老年人至少开了一种具有镇静作用的药物,一小部分人有较高的 SL。基线 SL 的增加与新发生的 AE、谵妄和跌倒的可能性更大相关,这突出表明在这个潜在脆弱的人群中需要进行最佳的药物治疗。

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