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主要的健康问题。这些情况是养老院发病率和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，抗胆碱能药物与显著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随这些药物的抗胆碱能活性水平而变化。此外，抑郁症等潜在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，因为这种疾病与严重的认知缺陷有关。尽管养老院的老人大量使用抗胆碱能药物，但对这些药物对老年抑郁症患者的认知影响知之甚少。本研究采用已验证的抗胆碱能药物量表（ADS），评估具有显著抗胆碱能活性药物对老年抑郁症患者的主要不良反应。本研究的目的是：(1)研究临床显著性抗胆碱能药物对老年抑郁症患者痴呆风险的影响；(2)评估临床显著性抗胆碱能药物对老年抑郁症患者认知能力的影响；(3)评估临床显著性抗胆碱能药物对老年抑郁症患者的其他中心不良反应。抗胆碱能药物暴露将根据ad抗胆碱能活性的四个水平（0到3）进行分类，重点是临床显著的高水平（2和3）抗胆碱能药物。以下假设将在老年抑郁症患者中进行检验：(i)高水平（2级或3级）抗胆碱能药物服用者比低水平（1级）抗胆碱能药物服用者患痴呆的风险更大；（ii）高水平抗胆碱能药物服用者的认知能力下降幅度大于低水平服用者；（iii）高剂量抗胆碱能药物的使用者比低剂量的使用者有更大的跌倒/骨折和全因死亡率的风险。本研究采用回顾性设计，纳入全国范围内年龄在60至65岁之间的老年养老院居民，以检验研究假设。临床丰富的最小数据集（MDS）与涉及A、B、D部分的医疗保险索赔数据相关联，将用于解决研究目标。不良反应的测量将包括轻度认知能力，痴呆，跌倒/骨折，以及医疗保险和MDS数据集中捕获的全因死亡率。该研究将涉及多重倾向评分方法，以调整跨抗胆碱能水平的选择偏差

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.