Cerebromicrovascular disease in elderly with diabetes

老年糖尿病患者的脑微血管疾病

• 批准号: 7526865
• 负责人: VERA NOVAK
• 金额: $ 60.92万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7526865
• 关键词: Adult; Affect; Age; Aging; Anterior; Atrophic; Attenuated; Biological Markers; Blood - brain barrier anatomy; Blood Flow Velocity; Blood flow; Brain; Brain Injuries; Carbon Dioxide; Cerebrospinal Fluid; Cerebrovascular Circulation; Cerebrum; Clinic; Clinical; Clinical Research; Cognition; Cognitive; Collaborations; Complications of Diabetes Mellitus; Control Groups; Data; Dementia; Diabetes Mellitus; Diabetic Angiopathies; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Doppler Ultrasound; Early Diagnosis; Elderly; Equation; Equilibrium; Functional disorder; Gerontology; Goals; Gray unit of radiation dose; Hemoglobin; Homeostasis; Hyperglycemia; Hypertension; Image; Impaired cognition; Impairment; Inflammation; Inflammatory; Institutes; Israel; Laboratories; Lead; Liquid substance; Magnetic Resonance Imaging; Maps; Massachusetts; Measurement; Measures; Medical center; Memory; Metabolic; Metabolism; Methods; Microcirculation; Modeling; Morbidity - disease rate; Neurology; Neuronal Dysfunction; Non-Insulin-Dependent Diabetes Mellitus; Ohio; Older Population; Outcome; Outcome Measure; Patients; Perfusion; Permeability; Population; Practice Guidelines; Prevention; Principal Investigator; Problem Solving; Psychiatry; Recovery; Regional Perfusion; Regulation; Rehabilitation Centers; Research; Resources; Risk; Severities; Severity of illness; Spin Labels; Stress; Stroke; Structure; Syncope; Techniques; Temporal Lobe; Translating; Universities; Vascular Dementia; Weight; aged; aging population; brain tissue; brain volume; cell injury; cerebral atrophy; cerebral hypoperfusion; cerebrovascular; cytokine; diabetes control; diabetes management; diabetic; diabetic patient; equilibration disorder; executive function; falls; feeding; follow-up; functional decline; functional outcomes; human very old age (85+); inflammatory marker; medical schools; middle cerebral artery; mortality; multidisciplinary; novel; novel diagnostics; pressure; public health relevance; response; socioeconomics; therapeutic target; white matter

DESCRIPTION (provided by applicant): Diabetes mellitus (DM) is a prevalent, costly condition with high morbidity and mortality. Our goal is to determine prospectively mechanisms by which type 2 DM alters cerebral microcirculation and contributes to brain tissue damage and cognitive decline in the elderly. The primary hypotheses are: 1. Hyperglycemia is a common mechanism for microvascular disease, disturbance in blood flow regulation and brain tissue damage in older adults with type 2 DM. 2. Inflammation contributes to neuroanatomical changes in periventricular white matter and white matter hyperintensities on MRI. 3. Cortical and subcortical atrophy in frontal and temporal regions manifests as executive dysfunction and impairment of balance in older adults with type 2 DM. Diabetes severity and higher hemoglobin A1C levels are associated with progressive decline in cerebral blood flow, cortical and subcortical brain volumes, and cognition and balance in older adults with type 2 DM. We will prospectively study 60 diabetic and 60 control subjects (50-85 years old, matched by age and hypertension) at baseline and after a two-year follow-up. In the Aim 1 we will determine the effects of type 2 DM on regional brain tissue volumes and perfusion, dynamics of cerebral autoregulation. In Aim 2 we determine the effects of inflammation on white matter integrity. In the Aim 3 we will determine longitudinally if higher hemoglobin A1C levels increase progression of cerebral blood flow dysregulation, brain atrophy and worsen cognitive and balance outcomes. Regional gray, white matter and cerebrospinal fluid volumes will be quantified using a segmentation method applied on T1- and T2- weighted images and perfusion maps, using a continuous arterial spin labeling (CASL) images at 3 Tesla MRI. White matter integrity will be determined from fluid attenuated inversion recovery (FLAIR) and diffusion tensor imaging (DTI) MRI. Dynamics of cerebral vasoregulation to CO2 challenge and orthostatic stress will be determined using Doppler ultrasound. We plan to use statistical structural equation modeling technique to characterize the mechanisms by which diabetes may lead to cognitive decline in older people, and to quantify interactions among metabolic diabetic disturbance, cerebral blood flow and brain atrophy. This study will provide new data and biomarkers on cerebral perfusion and functional outcomes in type 2 DM that can be used to initialize the efforts to implement brain protection as a new target prevention of DM complications. PUBLIC HEALTH RELEVANCE: Diabetes mellitus (DM) is a prevalent, costly condition with high morbidity and mortality that doubles the risk for stroke and dementia. DM affects blood flow regulation in the brain, that leads to brain damage and worsening of cognition and balance in older diabetic adults. This study will provide new data and biomarkers on cerebral perfusion and functional outcomes in type 2 DM, that can be used to initialize the efforts to implement brain protection as a new target for prevention of DM complications.

描述（由申请人提供）：糖尿病 (DM) 是一种普遍存在、费用高昂、发病率和死亡率较高的疾病。我们的目标是前瞻性地确定 2 型糖尿病改变大脑微循环并导致老年人脑组织损伤和认知能力下降的机制。主要假设是： 1. 高血糖是 2 型糖尿病老年人微血管疾病、血流调节紊乱和脑组织损伤的常见机制。 2. 炎症导致脑室周围白质的神经解剖学变化和 MRI 上的白质高信号。 3. 2型糖尿病老年人的额叶和颞区皮质和皮质下萎缩表现为执行功能障碍和平衡障碍。糖尿病严重程度和较高的糖化血红蛋白水平与 2 型糖尿病老年人的脑血流量、皮质和皮质下脑容量以及认知和平衡的逐渐下降有关。我们将在基线和两年随访后对 60 名糖尿病受试者和 60 名对照受试者（50-85 岁，年龄和高血压相匹配）进行前瞻性研究。在目标 1 中，我们将确定 2 型糖尿病对区域脑组织体积和灌注、脑自动调节动态的影响。在目标 2 中，我们确定炎症对白质完整性的影响。在目标 3 中，我们将纵向确定较高的糖化血红蛋白水平是否会加剧脑血流失调、脑萎缩以及认知和平衡结果恶化的进展。将使用应用于 T1 和 T2 加权图像和灌注图的分割方法，使用 3 特斯拉 MRI 的连续动脉旋转标记 (CASL) 图像来量化区域灰质、白质和脑脊液体积。白质完整性将通过液体衰减反转恢复 (FLAIR) 和扩散张量成像 (DTI) MRI 确定。将使用多普勒超声确定脑血管调节对二氧化碳挑战和直立性应激的动态。我们计划使用统计结构方程建模技术来表征糖尿病可能导致老年人认知能力下降的机制，并量化糖尿病代谢紊乱、脑血流量和脑萎缩之间的相互作用。这项研究将提供关于 2 型糖尿病脑灌注和功能结果的新数据和生物标志物，可用于启动实施脑保护作为预防 DM 并发症的新目标的努力。公众健康相关性：糖尿病 (DM) 是一种普遍存在且费用昂贵的疾病，发病率和死亡率很高，使中风和痴呆的风险增加一倍。糖尿病会影响大脑的血流调节，从而导致老年糖尿病患者的大脑损伤以及认知和平衡能力恶化。这项研究将提供关于 2 型糖尿病脑灌注和功能结果的新数据和生物标志物，可用于启动实施脑保护作为预防糖尿病并发症新目标的努力。