Predicting long-term cognitive outcomes and Alzheimer’s disease and related dementias after major noncardiac surgery for older adults

项目总结/摘要 高达10%的老年人在术后1年或更长时间内经历了持久的认知功能下降， 非心脏手术，这与高达50%的阿尔茨海默病和阿尔茨海默氏症的风险增加有关 疾病相关性痴呆（AD/ADRD）。然而，大多数老年人的认知能力不会受到伤害， 由于手术而享有更长的寿命和/或改善的功能。关于预期的信息很少 认知结果可用于指导老年人考虑择期手术，因为先前的研究 未纳入纵向术前轨迹，侧重于临床相关认知结局，或 旨在促进个性化预测。尽管它被称为“道德上的必要性”， 医生讨论不良术后认知结果作为手术知情同意书的一部分，他们缺乏 准确、个性化的信息，与患者分享。在这项研究中，我们建议使用大型，人口- 代表性的纵向数据源，以开发和验证长期临床预测模型 老年人择期大手术后的认知结局，包括AD/ADRD。我们将（AIM 1）使用 健康和退休研究（HRS），与医疗保险账单数据相关联，以开发临床预测模型 基于术前已知的因素来预测（a）记忆，（B）AD/ADRD的风险，和（c） 独立管理自己的财务和药物，这是日常生活中两项认知密集型的工具性活动 术后2年的IADL。在方法上，我们将平衡模型复杂性和临床 实用性和使用方法来解释选择性生存。我们将（AIM 2）增加临床预测 手术后发生并发症或不良事件的模型，例如，精神错乱，再次入院， 新发中重度疼痛。本目标的研究结果将加强对“最佳情况，最坏情况”的理解 认知结局（记忆、AD/ADRD和认知功能）纳入术前认知风险 讨论这些发现也将支持未来关于导致不良反应的关键机制的假设。 结果，指导术后管理的优先事项，以改善长期认知结果。最后， 我们将（AIM 3）再次使用国家健康和老龄化趋势研究对HRS模型进行外部验证 与医疗保险数据相关联，以评估预测记忆、AD/ADRD和IADL的模型的普遍性 手术后的独立经验证，这些模型可用于临床预测2年认知功能 结果，包括AD/ADRD风险，使老年人有准确的，个性化的信息， 无论是否进行手术，认知功能都将得到改善。这些信息将使长期认知纳入 手术共同决策的结果，这是老年手术患者的变革性进步。

PROJECT SUMMARY / ABSTRACT Up to 10% of older adults experience durable postoperative cognitive decline at 1 year or beyond after major noncardiac surgery, which is associated with up to 50% increased risk for Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD). However, most older adults will be cognitively unharmed by, and will enjoy longer life and/or improved function because of, surgery. Very little information about anticipated cognitive outcome is available to guide older adults considering elective surgery, because prior research has not incorporated longitudinal pre-surgical trajectories, focused on clinically relevant cognitive outcomes, or been designed to facilitate individualized predictions. Although it has been called “ethically imperative” that physicians discuss adverse postoperative cognitive outcomes as part of surgical informed consent, they lack accurate, individualized information to share with patients. In this study, we propose to use large, population- representative, longitudinal data sources to develop and validate clinical prediction models for long-term cognitive outcomes, including AD/ADRD, after elective major surgery in older adults. We will (AIM 1) use the Health and Retirement Study (HRS), linked to Medicare billing data, to develop clinical prediction models based on preoperatively-known factors to predict (a) memory, (b) risk of AD/ADRD, and (c) ability to independently manage one’s finances and medication, two cognitively-intensive instrumental activities of daily living (IADLs), at two years after surgery. Methodologically, we will balance model complexity with clinical practicality and use methods to account for selective survival. We will (AIM 2) augment the clinical prediction models with complications or adverse events that occur after surgery, e.g., delirium, hospital readmission, and new moderate-severe pain. Findings from this Aim will enhance understanding of “best case, worst case” cognitive outcomes (memory, AD/ADRD, and cognitive-functional) to include in preoperative cognitive risk discussion. These findings will also support future hypotheses about key mechanisms that lead to adverse outcomes, guiding priorities for post-surgical management to improve long-term cognitive outcomes. Finally, we will (AIM 3) externally validate the HRS models using the National Health and Aging Trends study, again linked to Medicare data, to assess generalizability of the models predicting memory, AD/ADRD, and IADL independence after surgery. After validation, these models can be used clinically to predict 2-year cognitive outcomes, including AD/ADRD risk, so that older adults have accurate, personalized information on the likely cognitive outcomes with or without surgery. This information will enable inclusion of long-term cognitive outcomes in surgical shared decision-making, a transformative advance for older surgical patients.