Effects of Biomedical Risk Factors on Neuro-cognition Using MRI: Long term follow-up of the Diabetes Control & Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Cohort

使用 MRI 研究生物医学危险因素对神经认知的影响：糖尿病控制的长期随访

• 批准号: 10455910
• 负责人: ALAN M JACOBSON
• 金额: $ 7.8万
• 依托单位: NYU LONG ISLAND SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-05 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10455910
• 关键词: Effects; Biomedical; Risk; Factors; Neuro

Abstract The extent, nature and pathogenesis of neuro-cognitive impairments among individuals with type 1 diabetes (T1DM) are poorly understood. Patients with T1DM are living longer and thus are commonly entering an age (50+) when such impairments become more evident, but are, as yet, understudied. Past, small studies suggest aspects of cognition, brain structure, function and chemistry that may be affected by T1DM and may increase in severity and clinical importance with aging. The Diabetes Control & Complications Trial/Epidemiology of Diabetes Interventions & Complications (DCCT/EDIC) study affords an unparalleled opportunity to use longitudinal data gathered over 30 years from early in the course of illness, among this well- characterized cohort, to examine important and unresolved questions about the frequency and pathogenesis of neuro-cognitive impairments as patients enter the age of highest risk. DCCT/EDIC participants have had continuously high rates of participation (currently 94% of the surviving cohort), and are now returning for an additional five years of follow-up (2017-2022) for ongoing and new biomedical assessments including evaluation of cognitive functioning and depression. This application, submitted in response to RFA-DK-16-007, will leverage available data collected in this cohort from past evaluations and from the new planned 5-year follow-up. We plan to assess effects of risk factors including: exposure to hyperglycemia as documented by HbA1c measurements during DCCT/EDIC, recurrent severe hypoglycemic events, variation in glycemia using continuous glucose monitoring (CGM ), history of hypertension, hyperlipidemia, and presence of micro- vascular and macro-vascular complications on the integrity of the brain evaluated by magnetic resonance imaging (MRI), and the association of brain changes with neuro-retinal degeneration assessed by a novel method-Ocular Coherence Tomography (OCT). We hypothesize that the presence of T1DM, prior conventional DCCT treatment assignment, elevated HbA1c levels and history of severe hypoglycemia will lead to reduced total brain volume, our primary outcome, and also result in detectable vascular, neuro-degenerative, neuro- chemical and functional changes assessed by MRI. In addition, we postulate that these primary risk factors in concert with other secondary risk factors (e.g.: glycemic variation, hypertension & micro-vascular and macro- vascular disease), will differentially affect frontal & temporal regions. Changes in the brain will be associated with decreased cognitive functioning, especially on measures of psychomotor efficiency. To reach these goals 400 T1DM subjects from the DCCT/EDIC cohort randomly selected to represent a broad range of biomedical outcomes will be compared with a non-diabetic control population (n=100) of similar age and social/educational background using identical cognitive and neuro-imaging techniques. Completion of these aims will determine key predictors of neuro-cognitive impairments in patients with T1DM and guide personalized strategies to mitigate this risk in providing clinical care for patients with T1DM.

抽象的 1 型糖尿病患者神经认知障碍的程度、性质和发病机制 （T1DM）人们知之甚少。 T1DM 患者的寿命更长，因此通常进入老年期 (50+) 当这种损伤变得更加明显时，但迄今为止尚未得到充分研究。过去的小型研究 提出可能受 T1DM 影响的认知、大脑结构、功能和化学方面的建议，并且可能 随着年龄的增长，其严重程度和临床重要性也会增加。糖尿病控制和并发症 糖尿病干预和并发症的试验/流行病学 (DCCT/EDIC) 研究提供了无与伦比的研究 有机会使用从病程早期开始 30 多年收集的纵向数据， 特征队列，检查有关频率和发病机制的重要且未解决的问题 当患者进入最高风险年龄时，会出现神经认知障碍。 DCCT/EDIC 参与者已经 持续高参与率（目前存活群体的 94%），现在正在回归 对正在进行的和新的生物医学评估进行额外五年的后续行动（2017-2022），包括 认知功能和抑郁的评估。本申请是响应 RFA-DK-16-007 提交的， 将利用从过去的评估和新计划的 5 年中收集的可用数据 后续行动。我们计划评估风险因素的影响，包括： 暴露于高血糖（如记录） DCCT/EDIC 期间的 HbA1c 测量、反复发生的严重低血糖事件、使用 连续血糖监测 (CGM)、高血压病史、高脂血症以及存在微量元素 通过磁共振评估血管和大血管并发症对大脑完整性的影响 成像（MRI），以及通过一种新的方法评估大脑变化与神经视网膜变性的关联 方法-眼相干断层扫描（OCT）。我们假设 T1DM 的存在 DCCT 治疗分配、HbA1c 水平升高和严重低血糖史将导致降低 总脑容量，我们的主要结果，也会导致可检测到的血管、神经退行性、神经- 通过 MRI 评估化学和功能变化。此外，我们假设这些主要风险因素 与其他次要危险因素（例如：血糖变化、高血压、微血管和宏观疾病）相一致 血管疾病），会对额叶和颞区产生不同的影响。大脑的变化会与之相关 认知功能下降，尤其是精神运动效率的衡量。为了实现这些目标 从 DCCT/EDIC 队列中随机选择的 400 名 T1DM 受试者代表了广泛的生物医学领域 结果将与年龄和社会/教育程度相似的非糖尿病对照人群（n = 100）进行比较 使用相同的认知和神经成像技术的背景。这些目标的完成将决定 T1DM 患者神经认知障碍的关键预测因子，并指导个性化策略 为 T1DM 患者提供临床护理可减轻这种风险。