Alzheimer's Supplement to ESRD-specific physiologic age

阿尔茨海默病对 ESRD 特定生理年龄的补充

• 批准号: 10286420
• 负责人: Mara A. McAdams DeMarco
• 金额: $ 40.84万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10286420
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Blood Pressure; Brain Injuries; Chronology; Clinical; Cognition; Cognitive; Communities; Consensus; Data; Delirium; Dementia; Diabetes Mellitus; Diagnosis; Diagnostic; Dialysis patients; Dialysis procedure; Disadvantaged; Documentation; Education; Educational Status; Elderly; End stage renal failure; Evaluation; Fluid Shifts; Funding; Hazard Models; Hypertension; Hypotension; Immunosuppression; Impaired cognition; Impairment; Incidence; Interleukin-6; Kidney; Kidney Transplantation; Knowledge; Lead; Longevity; Measures; Mediating; Methods; Modeling; Odds Ratio; Operative Surgical Procedures; Outcome; Patients; Perioperative; Perioperative complication; Pharmaceutical Preparations; Physiological; Population; Prospective cohort study; Public Health; Race; Records; Research; Risk; Risk Factors; Role; Secondary Hyperparathyroidism; Secondary to; System; TNF gene; Testing; Time; Transplant Recipients; Transplantation; Validity and Reliability; Vascular Dementia; Vascular Diseases; Weight; Work; base; cerebral atrophy; cognitive function; cognitive performance; cognitive testing; comorbidity; confusion assessment method; dementia risk; depressive symptoms; executive function; experience; follow-up; frailty; functional disability; improved; inflammatory marker; mortality; mortality risk; neurocognitive test; neurotoxic; novel; post-transplant; prognostic; prospective; public health relevance; screening; sex; symposium

ABSTRACT: RELEVANCE TO ADRD Only 13% of dialysis patients have normal cognition. Older end-stage renal disease (ESRD) patients are at risk for Alzheimer's disease and related dementias (ADRD) due to their advanced age, high burden of vascular disease, and comorbid conditions. Dialysis results in rapid fluid shifts that can lead to wide swings in blood pressure, cerebral atrophy, and brain injury; uremic metabolites are not fully cleared and impact cognitive function. Older dialysis patients have a 21-25% risk of a dementia diagnosis and 4-8% risk of an ADRD diagnoses; this is 19-fold and 7-fold higher than community-dwelling older adults without ESRD. Kidney transplantation (KT) is a growing treatment option for older adults with ESRD and improves cognitive function. However, even after careful pre-operative cognitive screening to identify the dialysis patients with existing dementia, post-KT incidence of dementia and ADRD is high. Compared to an ADRD risk of 0.6-0.9% for community-dwelling older adults, we found that 7.2-17.0% of older KT recipients received a diagnosis of ADRD. Yet, only half of patients who would meet diagnostic criteria for dementia receive a diagnosis suggesting that there is a substantial burden of undiagnosed ADRD among dialysis patients and KT recipients. An ADRD diagnosis doubles mortality risk for dialysis patients, and increases the risk of mortality and graft loss for KT recipients. ADRD is a clinical and public health challenge for this population, yet diagnosis of dementia notoriously underestimates the true incidence; <15% of ESRD patients with cognitive impairment have chart documentation. There is a clear knowledge gap surrounding which older ESRD patients will develop ADRD. Older ESRD patients experience a high burden of geriatric-specific risk factors for ADRD including frailty, depressive symptoms, and cognitive impairment. KT eliminates or reduces these ESRD-specific risk factors and improves cognitive function. However, there is a tradeoff: perioperative ADRD risk factors, like delirium and neurotoxic immunosuppression, may impact long-term ADRD risk. We will add novel assessments of ADRD and delirium to our prospective R01-funded study of frailty and aging among older (age≥55; n=3,000) KT candidates undergoing dialysis and older KT recipients, where global (MoCA) and domain-specific (TMT- A/B, AVLT) cognitive performance are already measured. We seek to: 1) To estimate the burden of pre- and post-KT dementia and ADRD among older ESRD patients; 2) To identify geriatric- and ESRD-specific ADRD risk factors among older ESRD patients; and 3) To test whether perioperative factors mediate the pre-KT risk for subsequent post-KT ADRD. Our findings will help clarify the risk factors and burden of ADRD among older ESRD patients. This work will be directly applicable to all older surgical patients who are at risk for perioperative complications like delirium and cognitive decline leading to long-term ADRD.

摘要：与ADRD相关 只有13％的透析患者具有正常的认知。较老的末期肾病（ESRD）患者处于危险之中 由于阿尔茨海默氏病和相关痴呆症（ADRD），由于其高年龄，血管燃烧高 疾病和合并症。透析导致快速流体变化，可能导致血液挥杆 压力，脑萎缩和脑损伤；尿毒症代谢产物未完全清除，并影响认知 功能。老年透析患者的痴呆诊断风险为21-25％，ADRD的风险为4-8％ 诊断；这比没有ESRD的社区老年人高19倍和7倍。肾 移植（KT）是ESRD老年人的增长治疗选择，并改善了认知功能。 但是，即使经过仔细的术前认知筛查，也可以确定现有的透析患者 痴呆症，痴呆症和ADRD的KT后事件很高。与ADRD风险为0.6-0.9％ 居住在社区的老年人，我们发现7.2-17.0％的年长KT接受者接受了诊断 adrd。但是，只有一半符合痴呆诊断标准的患者接受诊断 表明透析患者和KT接受者中未诊断的ADRD大量燃烧。 ADRD的诊断使透析患者的死亡风险增加一倍，并增加了死亡率和移植物损失的风险 ADRD是该人群的临床和公共卫生挑战，但诊断为痴呆症 众所周知，低估了真正的事件。 <15％的ESRD认知障碍患者具有图表 文档。围绕年龄较大的ESRD患者会出现ADRD的明显知识差距。 老年ESRD患者的老年特异性危险因素的ADRD高度燃烧，包括脆弱， 抑郁症状和认知障碍。 KT消除或减少了这些ESRD特定的风险因素 并提高认知功能。但是，有一个权衡：定期的ADRD风险因素，例如ir妄 神经毒性免疫抑制可能会影响长期ADRD风险。我们将添加对 在我们的前瞻性R01资助研究中，Adrd和Delirium toterive and衰老（年龄≥55; n = 3,000） KT候选者接受了透析和年长的KT接受者，其中全球（MOCA）和域特异性（TMT-） A/B，Avlt）认知表现已经测量。我们寻求：1）估计燃烧前和 年龄较大的ESRD患者的KT痴呆症和Adrd； 2）识别老年和ESRD特异性ADRD 老年ESRD患者的危险因素； 3）测试周期性因素是否介导了KT前风险 随后的KT后ADRD。我们的发现将有助于阐明年龄较大的ADRD的风险因素和燃烧 ESRD患者。这项工作将直接适用于所有有风险的老年外科手术患者 围手术期并发症，如del妄和认知下降，导致长期ADRD。