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Enhancing cerebral vasoreativity & cognition by intranasal insulin in T2DM

增强脑血管反应性

基本信息

批准号：
8049733
负责人：
VERA NOVAK
金额：
$ 21.38万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8049733
关键词：
3-Dimensional Acute Address Adult Affect Age Area Arkansas Atherosclerosis Atrophic Attention Autonomic Pathways Binding Biometry Blood - brain barrier anatomy Blood Vessels Brain Bypass Carbon Dioxide Center for Translational Science Activities Cerebrospinal Fluid Cerebrovascular Circulation Cerebrum Chronic Clinic Clinical Clinical Management Clinical Research Clinical Sciences Cognition Cognitive Collaborations Control Groups Crossover Design Data Dementia Diabetes Mellitus Diabetic Angiopathies Disease Doctor of Philosophy Dose Double-Blind Method Education Elderly Goals Homeostasis Hyperglycemia Hypothalamic structure Image Impaired cognition Impairment Insulin Insulin Receptor Intranasal Administration Israel Knowledge Laboratories Learning Limbic System Longitudinal Studies Magnetic Resonance Imaging Massachusetts Measurement Measures Medical center Memory Motor Neurology Neuronal Dysfunction Neurons Non-Insulin-Dependent Diabetes Mellitus Patients Performance Perfusion Pilot Projects Placebo Control Placebos Population Prevention Preventive Principal Investigator Psychiatry Regional Perfusion Regulation Research Resources Risk Factors Spin Labels Stroke Syncope Trigeminal System Universities Vascular Dementia Washington base cell injury cerebrovascular cognitive function design diabetic diabetic patient executive function falls frontal lobe functional decline gray matter improved medical schools mouse model multidisciplinary new therapeutic target older patient pressure public health relevance receptor therapeutic target translational study white matter

项目摘要

DESCRIPTION (provided by applicant): Type 2 diabetes mellitus (T2DM) is a major risk factor for vascular dementia. DM alters insulin transport across blood-brain barrier affecting perfusion and neuronal function. Intranasal administration enables to effectively deliver insulin to the brain. Clinical studies demonstrated improvement of cognitive function and memory in healthy and cognitively impaired people. Our goal is to determine the acute effects of intranasal insulin on regional perfusion and cognition in older diabetic adults. We propose a pilot study to examine the effects of a single dose of intranasal insulin on regional vasoreactivity and cognitive functions in 30 subjects with T2DM and 30 healthy controls >50 years old using a double blinded, placebo-controlled, cross-over design. Aim 1: We will determine the acute effects of a single 40-IU dose of intranasal insulin vs. placebo on regional perfusion and vasoreactivity to CO2 challenge measured by 3-D continuous arterial spin labeling (CASL) MRI at 3 Tesla in the control and diabetic groups. We will use transcranial Doppler to determine effects on intranasal insulin vs. placebo on dynamic autoregulation based on measurements of beat-to-beat pressure-flow velocity relationship. Aim 2: We will determine whether intranasal insulin improves cognitive functioning including attention, memory and executive function in older diabetic patients as compared with placebo and the control group. This translational study will address an important area about the effects of intranasal insulin on cerebral blood flow regulation and cognition in older diabetic people that has not been studied. Intranasal insulin administration may provide a novel therapeutic target for prevention and treatment of microvascular disease and cerebrovascular complications of T2DM. If successful, this approach may have significant impact on clinical management of large population of older adults with T2DM. PUBLIC HEALTH RELEVANCE: Diabetes mellitus is a major risk factor for both large and small vessel atherosclerosis, strokes, and vascular dementia. This pilot study aims to determine the efficacy of intranasal insulin to improve cerebral vasoreactivity and to explore the effects on cognitive function in older diabetic adults. If proven effective, intranasal insulin may become a new preventive and therapeutic target for treatment of cerebromicrovascular disease in older diabetic patients.

描述（由申请人提供）：2 型糖尿病 (T2DM) 是血管性痴呆的主要危险因素。 DM 改变胰岛素跨血脑屏障的转运，影响灌注和神经元功能。鼻内给药能够有效地将胰岛素输送到大脑。临床研究表明，健康人和认知障碍人士的认知功能和记忆力均得到改善。我们的目标是确定鼻内胰岛素对老年糖尿病患者区域灌注和认知的急性影响。我们提出了一项初步研究，采用双盲、安慰剂对照、交叉设计，检查单剂量鼻内胰岛素对 30 名 T2DM 受试者和 30 名 50 岁以上健康对照者的局部血管反应性和认知功能的影响。目标 1：我们将确定单次 40 IU 剂量的鼻内胰岛素与安慰剂相比对对照组和糖尿病组的区域灌注和 CO2 激发血管反应性的急性影响，通过 3 特斯拉连续动脉旋转标记 (CASL) MRI 测量。我们将使用经颅多普勒根据逐搏压力-血流速度关系的测量来确定鼻内胰岛素与安慰剂对动态自动调节的影响。目标 2：我们将确定与安慰剂和对照组相比，鼻内胰岛素是否可以改善老年糖尿病患者的认知功能，包括注意力、记忆力和执行功能。这项转化研究将探讨鼻内胰岛素对老年糖尿病患者脑血流调节和认知影响的一个重要领域，这一领域尚未得到研究。鼻内胰岛素给药可能为预防和治疗T2DM微血管疾病和脑血管并发症提供新的治疗靶点。如果成功，这种方法可能会对大量老年 T2DM 患者的临床管理产生重大影响。公共卫生相关性：糖尿病是大血管和小血管动脉粥样硬化、中风和血管性痴呆的主要危险因素。这项初步研究旨在确定鼻内胰岛素改善脑血管反应性的功效，并探讨其对老年糖尿病患者认知功能的影响。如果证明有效，鼻内胰岛素可能成为治疗老年糖尿病患者脑微血管疾病的新预防和治疗靶点。