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：ADRD的相关性 仅有13%的透析患者认知功能正常。老年终末期肾病（ESRD）患者面临风险 对于阿尔茨海默病和相关痴呆（ADRD），由于他们的高龄，高血管负担， 疾病和合并症。透析导致液体快速转移，可能导致血液大幅波动 血压、脑萎缩和脑损伤;尿毒症代谢物未完全清除，影响认知能力 功能老年透析患者有21-25%的痴呆诊断风险和4-8%的ADRD风险 诊断;这比没有ESRD的社区居住老年人高19倍和7倍。肾 移植（KT）是老年ESRD患者日益增长的治疗选择，并可改善认知功能。 然而，即使经过仔细的术前认知筛查，以确定透析患者是否存在 痴呆，KT后痴呆和ADRD的发病率高。与ADRD风险0.6-0.9%相比， 在社区居住的老年人中，我们发现7.2-17.0%的老年KT接受者被诊断为 ADRD。然而，只有一半符合痴呆症诊断标准的患者得到诊断， 这表明在透析患者和KT接受者中存在大量未诊断的ADRD负担。 ADRD诊断使透析患者的死亡风险增加一倍，并增加死亡和移植物丢失的风险 对于KT接受者。ADRD是这一人群的临床和公共卫生挑战，但痴呆症的诊断 众所周知，这低估了真实的发病率; <15%的患有认知障碍的ESRD患者有图表 文献.关于老年ESRD患者是否会发展为ADRD，存在明显的知识差距。 老年ESRD患者经历了ADRD的老年特异性风险因素的高负担，包括虚弱， 抑郁症状和认知障碍KT消除或减少了这些ESRD特异性风险因素 改善认知功能。然而，有一个权衡：围手术期ADRD风险因素，如谵妄 和神经毒性免疫抑制，可能会影响长期ADRD风险。我们将增加新的评估， 我们的前瞻性R 01资助的老年人虚弱和衰老研究中的ADRD和谵妄（年龄≥55岁; n= 3，000） 接受透析的KT候选人和年龄较大的KT接受者，其中全球（莫卡）和特定领域（TMT- A/B，AVLT）认知表现已经测量。我们寻求：1）估计前的负担， 老年ESRD患者中的KT后痴呆和ADRD; 2）识别老年和ESRD特异性ADRD 老年ESRD患者中的危险因素; 3）检测围手术期因素是否介导了KT前风险 用于随后的KT后ADRD。我们的研究结果将有助于阐明老年人ADRD的危险因素和负担， ESRD患者。这项工作将直接适用于所有老年手术患者谁是在风险 围手术期并发症，如谵妄和认知能力下降，导致长期ADRD。