Epidemiology of potentially inappropriate medication use and risk for mild cognitive impairment and dementia among ARIC, Look AHEAD, and MESA

项目概要/摘要 在老年人（年龄≥65岁）中使用可能不适当的药物（PIM）导致可预防的 不良健康事件，包括住院和死亡。某些被归类为 因为PIM与痴呆症的更大风险相关，证明其作用于中枢和外周神经系统， 系统并阻断特定神经递质的作用（例如，抗胆碱能药物阻断乙酰胆碱）。登记处─ 研究表明，PIM的使用增加了老年人与阿尔茨海默病的个人， 相关痴呆（AD/RD）和匹配的健康对照。然而，老年人使用PIM的流行病学 成年期尚未在多族裔社区群体中进行评估，也未根据生活方式进行评估 干预由于PIM的使用会导致可避免的并发症，因此我们需要了解PIM的流行病学 分别用于对干预措施的反应和与随后的认知并发症有关。识别 生活方式干预是否可以减少PIM的使用并预防轻度认知障碍和痴呆症， 具有重大的临床和公共卫生意义。 该提案将利用流行病学研究和临床试验的数据来估计PIM 三项大型多种族和地理多样性研究中的患病率、发病率和纵向变化 社区动脉粥样硬化风险研究（ARIC），糖尿病健康行动研究， 多民族研究的动脉粥样硬化。本研究将估计（目标1）PIM使用的流行率和影响因素 与PIM使用相关，（目标2）在老年人中PIM使用的纵向变化以及对PIM使用的响应。 强化生活方式干预减肥，以及（目标3）PIM使用与事件之间的关联 MCI/痴呆和脑病理学。 这项工作是重要的和创新的，因为它将提供估计的PIM使用之间的多种族的队列 和一个新的研究资源展望未来和梅萨调查（PIM使用的表征）。这 该提案还将评估生活方式干预对PIM使用纵向变化的影响， 解开PIM使用和AD/RD之间的时间关联。我们设计的每一个目标都是为了解决 我们对PIM使用流行病学的理解存在重大差距，以及对老年人进行干预的潜力 减少由于PIM使用导致的AD/RD相关发病率和死亡率。我们的团队有研究技能，经验， 并提供资源，以严格和有效的方式实现这些目标。这项工作的结果将提供 减少PIM使用和预防AD/RD的治疗策略的经验证据，并评估PIM是否 使用与其他老化相关的条件有关。

Project Summary/Abstract Use of potentially inappropriate medications (PIMs) among older adults (age ≥65 years) result in preventable adverse health events, including hospitalization and mortality. Certain individual medications that are classified as PIMs are associated with greater risk for dementia, demonstrated to act on the central and peripheral nervous system and block the action of specific neurotransmitters (e.g., anticholinergics block acetylcholine). Registry- based studies show that PIM use increases over older adulthood for individuals with Alzheimer’s disease and related dementias (AD/RD) and matched healthy controls. However, epidemiology of PIM use over older adulthood has not been assessed in multi-ethnic community-based cohorts or in response to a lifestyle intervention. Because PIM use results in avoidable complications, we need to understand epidemiology of PIM use in response to interventions and in relation to subsequent cognitive complications, respectively. Identifying whether lifestyle interventions can reduce PIM use and prevent mild cognitive impairment and dementia would have major clinical and public health implications. This proposal will leverage data from epidemiological studies and a clinical trial to provide estimates of PIM prevalence, incidence, and longitudinal change among three large multi-ethnic and geographically diverse study populations: the Atherosclerosis Risk in Communities (ARIC) Study, Action for Health in Diabetes Study, and Multi-Ethnic Study of Atherosclerosis. This research will estimate (Aim 1) prevalence of PIM use and factors associated with PIM use, (Aim 2) longitudinal change in PIM use during older adulthood and in response to an intensive lifestyle intervention for weight loss, and (Aim 3) the association between PIM use and incident MCI/dementia and brain pathology. This work is significant and innovative because it will provide estimates of PIM use among multi-ethnic cohorts and a new research resource for Look AHEAD and MESA investigators (characterization of PIM use). This proposal will also assess the effect of a lifestyle intervention on longitudinal change in PIM use and will help disentangle the temporal association between PIM use and AD/RD. We have designed each aim to address a critical gap in our understanding of the epidemiology of PIM use, and potential for interventions in older adulthood to reduce AD/RD-related morbidity and mortality due to PIM use. Our team has the research skills, experience, and resources to address these aims in a rigorous and efficient manner. The findings from this work will provide empirical evidence for treatment strategies to reduce PIM use and prevent AD/RD, and to assess whether PIM use is associated with other aging-related conditions.