Anticholinergics and Cognitive Decline in the Elderly with Depression

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。这些情况是疗养院发病率和卫生保健负担的主要来源，显著影响患者的生活质量。越来越多的证据表明，抗胆碱能药物与老年人的显著中枢不良反应（包括认知障碍和痴呆）相关。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，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的中枢介导作用的影响，这是由于与疾病相关的显著认知缺陷。尽管显着使用抗胆碱能药物的老年疗养院居民，很少有人知道这些药物在老年抑郁症的认知影响。本研究拟采用抗胆碱能药物量表（ADS）评价抗胆碱能药物对老年抑郁症患者的中枢副作用。拟开展的研究旨在：（1）检查老年抑郁症患者使用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老年抑郁症患者认知能力的影响，（3）评估具有临床意义的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4种抗胆碱能活性水平（0 - 3）进行分类，重点关注具有临床意义的高水平（2和3）抗胆碱能药物。以下假设将在患有抑郁症的老年居民中进行验证：（i）高水平的老年人患痴呆症的风险更大（2级或3级）抗胆碱能药物使用者比低水平（1级）使用者的认知能力下降更大;（ii）高水平抗胆碱能药物使用者比低水平使用者的认知能力下降更大;和（iii）高水平抗胆碱能药物使用者的福尔斯/骨折全因死亡率风险高于低水平使用者。一项回顾性设计，涉及大型国家队列的老年疗养院居民> 65岁，将用于测试研究假设。临床上丰富的最小数据集（MDS）与涉及A、B和D部分的Medicare索赔数据相关，将用于解决研究目标。不良反应的指标将包括轻度认知能力、痴呆、福尔斯/骨折和Medicare和MDS数据集中采集的全因死亡率。该研究将涉及多重倾向评分方法，以调整抗胆碱能药物水平之间的选择偏倚。 安德森行为模型的多变量背景。将使用倾向评分校正的多变量分析（包括考克斯模型）评价抗胆碱能药物的安全性特征。拟议的调查将提供一个强有力的证据基础，抗胆碱能药物的中枢不良反应的特点，从而有助于优化抗胆碱能药物的使用，并加强ADS作为护理质量的措施，抑郁症在疗养院。

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.