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

项目摘要/摘要 在老年人(≥65岁)中使用可能不合适的药物(PIM)导致可预防的 不良健康事件，包括住院和死亡。某些单独的药物被归类 因为PIM与患痴呆症的风险更高，显示出对中枢和外周神经的作用 并阻断特定神经递质的作用(例如，抗胆碱能药阻断乙酰胆碱)。注册处- 基础研究表明，阿尔茨海默病患者的PIM使用量随着年龄的增长而增加 相关痴呆患者(AD/RD)和匹配的健康对照组。然而，老年人使用PIM的流行病学研究 成年期没有在以多种族社区为基础的队列中或根据一种生活方式进行评估 干预。由于PIM的使用会导致可避免的并发症，我们需要了解PIM的流行病学 分别用于应对干预和与随后的认知并发症有关的使用。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影响。 这项建议将利用流行病学研究和临床试验的数据来提供对PIM的估计 三项大型多民族和地理差异研究的患病率、发病率和纵向变化 人群：社区动脉粥样硬化风险(ARIC)研究，糖尿病健康行动研究，以及 动脉粥样硬化的多种族研究。这项研究将评估(目标1)PIM使用的普及率和因素 与PIM使用相关，(目标2)老年期间PIM使用的纵向变化以及对 密集的生活方式干预以减轻体重，以及(目标3)使用PIM与事件之间的关联 MCI/痴呆症和脑病理学。 这项工作具有重大意义和创新性，因为它将为多民族人群中PIM的使用提供估计 以及为展望未来和MESA调查人员提供的新研究资源(PIM使用的特征)。这 该提案还将评估生活方式干预对PIM使用的纵向变化的影响，并将有助于 理清PIM使用和AD/RD之间的时间关联。我们设计的每个目标都是为了解决 我们对PIM使用的流行病学以及对老年干预的可能性的理解存在严重差距 以减少由于使用PIM而导致的AD/RD相关的发病率和死亡率。我们的团队有研究技能，经验， 和资源，以严格和有效的方式实现这些目标。这项工作的发现将提供 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 使用与其他与衰老相关的疾病有关。

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.