Enhancement of cerebral vasoreactivity and cognition by intranasal insulin in typ

鼻内胰岛素对典型患者脑血管反应性和认知的增强作用

• 批准号: 7898116
• 负责人: VERA NOVAK
• 金额: $ 25.19万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7898116
• 关键词: 3-Dimensional; Acute; Address; Adult; Affect; Age; Area; Arkansas; Arts; Atherosclerosis; Atrophic; Attention; Autonomic Pathways; Binding; Biometry; Blood - brain barrier anatomy; Brain; Bypass; Carbon Dioxide; Center for Translational Science Activities; Cerebrospinal Fluid; Cerebrovascular Circulation; Cerebrum; Chronic; Clinic; Clinical; Clinical Management; Clinical Research; Cognition; Cognitive; Collaborations; Control Groups; Crossover Design; Data; Dementia; Diabetes Mellitus; Diabetic Angiopathies; Disease; Doctor of Philosophy; Dose; Double-Blind Method; Education; Elderly; Goals; Gray unit of radiation dose; 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; Metabolism; 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; improved; medical schools; mouse model; multidisciplinary; new therapeutic target; older patient; pressure; public health relevance; receptor; therapeutic target; translational study; white matter

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，健康和认知受损的人的认知功能和记忆的改善。我们的目标是确定鼻内胰岛素对老年糖尿病成年人区域灌注和认知的急性影响。我们提出了一项试点研究，以检查单个剂量的鼻内胰岛素对30名T2DM和30个健康对照受试者的区域血管反应性和认知功能的影响，> 50年> 50年，使用双重盲，安慰剂对照，交叉的设计。目标1：我们将确定单个40-iu剂量的鼻内胰岛素与安慰剂对区域灌注和对二氧化碳挑战的区域灌注和血管反应性的急性作用，该挑战在对照组和糖尿病组中通过3泰斯拉的3连续动脉自旋标记（CASL）MRI测量。我们将使用经颅多普勒来确定对鼻内胰岛素与安慰剂与安慰剂对动态自动调节的影响，基于对Beat-Beat压力流速度关系的测量。 AIM 2：我们将确定与安慰剂和对照组相比，鼻内胰岛素是否改善了糖尿病患者的注意力，记忆和执行功能，包括注意力，记忆和执行功能。这项翻译研究将介绍一个重要的领域，介绍鼻内胰岛素对尚未研究的老年糖尿病患者脑血流调节和认知的影响。鼻内胰岛素给药可为预防和治疗T2DM的微血管疾病和脑血管并发症提供新的治疗靶标。如果成功，这种方法可能会对大量T2DM老年人人群的临床管理产生重大影响。 公共卫生相关性： 糖尿病是大血管硬化，中风和血管性痴呆的主要危险因素。这项试点研究旨在确定鼻内胰岛素改善脑血管反应性的功效，并探索老年糖尿病成年人认知功能的影响。如果证明有效，鼻内胰岛素可能会成为老年糖尿病患者脑血管疾病的新预防和治疗靶标。