Anticholinergics and Cognitive Decline in the Elderly with Depression

描述(申请人提供)：认知功能减退和痴呆症是老年人的主要健康问题。这些疾病是养老院发病率和医疗负担的主要来源，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副作用有关，包括老年人的认知障碍和痴呆症。不良反应的程度可能会因这些药物的抗胆碱能活性水平而异。此外，抑郁症等潜在疾病会使老年人更容易受到抗胆碱药物的中枢调节作用，因为与这种疾病相关的严重认知缺陷。尽管在养老院的老年居民中大量使用抗胆碱能药物，但对这些药物对患有抑郁症的老年患者的认知影响知之甚少。利用先前验证的抗胆碱能药物量表(ADS)，这项拟议的研究将评估具有显著抗胆碱能活性的药物在老年抑郁症患者中的中心不良反应概况。本研究的目的是：(1)研究抑郁症老年居民服用临床显著抗胆碱能药物后痴呆的风险；(2)评估临床显著抗胆碱能药物对抑郁症老年居民认知功能的影响；(3)评估临床显著抗胆碱能药物对老年抑郁症患者的其他中枢不良反应。抗胆碱能药物暴露将根据ADS的抗胆碱能活性(0到3)的四个级别进行分类，重点是临床上有意义的、高水平(2和3)的抗胆碱药物。将在患有抑郁症的老年居民中检验以下假设：(I)高水平(2级或3级)抗胆碱能药物使用者比低水平(1级)使用者患痴呆症的风险更大；(Ii)高水平抗胆碱药物使用者的认知能力比低水平使用者更大；以及(Iii)高水平抗胆碱药物使用者比低水平使用者有更大的跌倒/骨折风险和全因死亡率。一项涉及65岁的全国老年养老院居民的回溯性设计将被用来检验研究假设。临床丰富的最小数据集(MDS)关联的联邦医疗保险索赔数据涉及A、B和D部分，将用于解决研究目标。不良反应的衡量标准将包括轻微的认知表现、痴呆症、跌倒/骨折以及在Medicare和MDS数据集中记录的所有原因死亡率。这项研究将涉及一种多倾向性评分方法，以调整不同抗胆碱能水平之间的选择偏差 安徒生行为模型的多元背景。倾向评分调整后的多变量分析，包括COX模型，将用于评估抗胆碱类药物的安全性。这项拟议的研究将为抗胆碱药物的中枢不良反应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措施的作用。 公共卫生相关性：尽管老年疗养院居民大量使用抗胆碱能药物，但对这些药物在老年抑郁症患者中的不良反应情况知之甚少。拟议的调查将为抗胆碱药物的中枢不良反应提供强有力的证据基础，并加强对抗胆碱能药物量表作为长期护理中的护理质量衡量标准的支持。此外，这些发现将有利于卫生保健提供者和政策制定者优化老年人抗胆碱能药物的使用，并将有助于提高这一弱势群体的护理质量

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. PUBLIC HEALTH RELEVANCE: Despite significant use of anticholinergic medications in elderly nursing home residents, little is known about the adverse effects profile of these agents in the elderly with depression. The proposed investigation will provide a strong evidence base for central adverse effects of anticholinergics and strengthen support for the Anticholinergic Drug Scale as a quality of care measure in long term care. In addition, the findings will be beneficial to health care providers and policy makers to optimize anticholinergic medication use in the elderly and will be instrumental in improving the quality of care in this vulnerable population