Anticholinergics and Cognitive Decline in the Elderly with Depression

抗胆碱能药物与老年抑郁症患者的认知能力下降

• 批准号: 8708817
• 负责人: Rajender R Aparasu
• 金额: $ 21.51万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8708817
• 关键词: Anticholinergics; Cognitive; Decline; Elderly; Depression

DESCRIPTION (provided by applicant): Cognitive decline and dementia are major health concerns in the elderly. These conditions are a major source of morbidity and health care burden in nursing homes that significantly affect patients' quality of life. There is accumulating evidence that anticholinergic medications are associated with significant central adverse effects including cognitive impairment and dementia in the elderly. The extent of the adverse effect may vary with the level of anticholinergic activity of these medications. Furthermore, underlying diseases like depression can make the elderly more susceptible to centrally mediated effects of anticholinergics due to significant cognitive deficits associated with the disease. Despite significant use of anticholinergic medications in the elderly nursing home residents, little is known about the cognitive impact of these agents in the elderly with depression. Using the previously validated Anticholinergic Drug Scale (ADS), the proposed study will evaluate the central adverse effects profile of medications with significant anticholinergic activity in the eldrly residents with depression. The aims of the proposed research are to: (1) examine the risk of dementia associated with clinically significant anticholinergics in the elderly residents with depression, (2) assess the impact of clinically significant anticholinergics on cognitive performance in the elderly residents with depression, and (3) evaluate other central adverse effects of clinically significant anticholinergics in the elderly residents with depression. Anticholinergic medication exposure will be classified based on the four levels of anticholinergic activity (0 to 3) of ADS, with a focus on clinically significant, high level (2 and 3) anticholinerics. The following hypotheses will be tested among elderly residents with depression that: (i) there is greater risk for dementia among high-level (level 2 or 3) anticholinergic users than low-level (level 1) users; (ii) there is greater decline in cognitive performance among high-level anticholinergics users than low-level users; and (iii) there is greater risk for falls/fractures an all-cause mortality among high-level anticholinergics than low-level users. A retrospective design involving large national cohorts of elderly nursing home residents > 65 years will be used to test the study hypotheses. Clinically rich Minimum Data Set (MDS) linked Medicare claims data involving Parts A, B, and D will be used to address the research objectives. The measures of adverse effects will include mild cognitive performance, dementia, falls/fractures, and all-cause mortality captured in Medicare and MDS datasets. The study will involve a multiple propensity score approach to adjust for the selection bias across anticholinergic levels within the multivariate context of the Andersen Behavioral Model. Propensity score adjusted multivariate analyses including Cox models will be used to evaluate the safety profile of anticholinergics. The proposed investigation will provide a strong evidence base regarding central adverse effects profile of anticholinergics and thereby help to optimize anticholinergic use and strengthen the ADS as a quality of care measure for depression in nursing homes.

描述（由申请人提供）：认知能力下降和痴呆是老年人的主要健康问题。这些病症是疗养院发病率和医疗保健负担的主要来源，严重影响患者的生活质量。越来越多的证据表明，抗胆碱能药物与严重的中枢不良反应有关，包括老年人的认知障碍和痴呆。不良反应的程度可能因这些药物的抗胆碱能活性水平而异。此外，由于与疾病相关的显着认知缺陷，抑郁症等基础疾病可能使老年人更容易受到抗胆碱能药物中枢介导的影响。尽管老年疗养院居民大量使用抗胆碱能药物，但人们对这些药物对患有抑郁症的老年人的认知影响知之甚少。使用先前验证的抗胆碱能药物量表（ADS），拟议的研究将评估具有显着抗胆碱能活性的药物对患有抑郁症的老年居民的主要不良反应概况。拟议研究的目的是：（1）检查患有抑郁症的老年居民与具有临床意义的抗胆碱能药物相关的痴呆风险，（2）评估具有临床意义的抗胆碱能药物对患有抑郁症的老年居民认知能力的影响，以及(3)评估具有临床意义的抗胆碱能药物对患有抑郁症的老年居民的其他中枢不良反应。抗胆碱能药物暴露将根据 ADS 的四个抗胆碱能活性水平（0 至 3）进行分类，重点是具有临床意义的高水平（2 和 3）抗胆碱药。以下假设将在患有抑郁症的老年居民中进行检验：(i) 高水平（2 级或 3 级）抗胆碱能使用者比低水平（1 级）抗胆碱能使用者患痴呆症的风险更大； (ii) 高剂量抗胆碱能药物使用者的认知能力下降幅度大于低剂量使用者； (iii) 高剂量抗胆碱能药物使用者比低剂量使用者有更大的跌倒/骨折和全因死亡风险。将使用一项涉及全国 65 岁以上老年疗养院居民的大型队列的回顾性设计来检验研究假设。涉及 A、B 和 D 部分的临床丰富的最小数据集 (MDS) 链接的医疗保险索赔数据将用于实现研究目标。不良影响的衡量标准包括医疗保险和 MDS 数据集中记录的轻度认知表现、痴呆、跌倒/骨折和全因死亡率。该研究将涉及多重倾向评分方法，以调整抗胆碱能水平的选择偏差 安徒生行为模型的多元背景。包括 Cox 模型在内的倾向评分调整多变量分析将用于评估抗胆碱能药物的安全性。拟议的调查将为抗胆碱能药物的主要不良反应概况提供强有力的证据基础，从而有助于优化抗胆碱能药物的使用并加强 ADS 作为疗养院抑郁症护理质量的措施。