Cognitive prehabilitation to prevent Alzheimer's disease after kidney transplantation

摘要 在美国的130,000名老年(≥50)肾移植(KT)接受者中，我们估计有19%的人经历了 KT后认知能力下降，使他们患阿尔茨海默病和相关痴呆(ADRD)的风险增加。 与社区老年人10年ADRD风险0.6%-0.9%相比，ADRD诊断的风险 对于老年受助者来说是1.0%-6.7%；总体而言，7.2%-17.0%的老年受助者在10%内被诊断为痴呆症 多年来的KT。然而，ADRD的真正负担要高得多，因为只有一半的患者会 符合诊断标准的痴呆症患者得到诊断。KT后ADRD诊断导致残疾和 依赖，并使患者死亡风险增加2.4倍，移植物丢失风险增加1.5倍。10分钟内 经过多年的ADRD诊断，88.6%的老年受者已经死亡，38.9%的人经历了移植物丢失。 这些初步数据来自我目前由美国国立卫生研究院资助的研究：1.前瞻性队列研究：12岁 KT患者的脆弱性和认知功能研究；2.随机对照试验：干预措施的2x2因素随机对照试验 维持血液透析患者的认知功能。我已经建立了良好的记录，而且 在老龄化和肾脏流行病学的交叉点建立了一个研究计划，作为 这是职业生涯中期的独立科学家(K02)奖项申请。通过这次研究，我认识到 只关注身体衰老，而不了解认知衰老，就会给人一幅不完整的老年图景 KT患者。随着我在2022年过渡到更多的行政职责，我无法扩展到ADRD研究和 与神经认知研究人员建立协作关系。这个K02会促进我的研究 通过让我有机会专注于职业发展，让我有机会 扩展我的研究组合，将ADRD包括在内。我的长期职业目标是建立一个可持续的 研究项目侧重于KT接受者的身体和认知老化。为了实现这些目标，我 争取受保护的时间来获取所需的知识和技能：1.将ADRD研究纳入我的 现有的研究档案；2.制定科学方案，研究老年KT的认知康复 接受者；以及3.建立一个全国性的肾脏老化研究网络，将在新的研究上进行合作 并指导初级教职员工。通过用受保护的时间取代行政职责，K02机制将允许 我要实现我的长期职业目标，即建立一个专注于物理方面的可持续研究计划 KT患者的认知老化。我会充分利用K02独立科学家 机制提供：ADRD研究培训，开发可持续的研究基础设施，并最终 影响了100,000名在等待KT期间身体和认知能力下降的患者的生活。

ABSTRACT Of the 130,000 older (≥50) kidney transplant (KT) recipients in the US, we have estimated that 19% experience post-KT cognitive decline putting them at elevated risk of Alzheimer’s disease and related dementias (ADRD). Compared to a 10-year ADRD risk of 0.6-0.9% for community-dwelling older adults, the risk of ADRD diagnosis is 1.0%-6.7% for older recipients; overall, 7.2-17.0% of older recipients receive a dementia diagnosis within 10 years of KT. Yet, the true burden of ADRD is substantially higher given that only half of patients who would meet diagnostic criteria for dementia receive a diagnosis. A post-KT ADRD diagnosis leads to disability and dependence, and increases a patient’s risk of mortality 2.4-fold and their risk of graft loss 1.5-fold. Within 10 years of an ADRD diagnosis, 88.6% of older recipients have died and 38.9% have experienced graft loss. These preliminary data arise from my current NIH funded research: 1. Prospective cohort study: 12-year-old study of frailty and cognitive function among KT patients; and 2. RCT: 2x2 factorial RCT of interventions to preserve cognitive function among patients initiating hemodialysis. I have established a strong track record and built a research program at the intersection of aging and renal epidemiology which serves as a foundation for this mid-career Independent Scientist (K02) award application. Through this research I have realized that focusing on physical aging without also understanding cognitive aging provides an incomplete picture of older KT patients. As I transition to more administrative duties in 2022, I am unable to expand to ADRD research and develop collaborative relationships with neurocognitive investigators. This K02 will advance my research career by affording me the opportunity for dedicated time to concentrate efforts on career development to expand my research portfolio to include ADRD. My long-term career objective is to establish a sustainable research program focused on physical and cognitive aging among KT recipients. To accomplish these goals, I seek protected time to acquire the knowledge and skills needed: 1. To integrate ADRD research into my existing research portfolio; 2. To develop scientific protocols to study cognitive prehabilitation for older KT recipients; and 3. To establish a national renal aging research network that will collaborate on new research and mentor junior faculty. By replacing administrative duties with protected time, the K02 mechanism will allow me to achieve my long-term career goal of establishing a sustainable research program focused on physical and cognitive aging among KT patients. I will take full advantage of what the K02 Independent Scientist mechanism offers: training in ADRD research, developing a sustainable research infrastructure, and ultimately impacting the lives of the 100,000 patients who experience physical and cognitive decline while waiting for KT.