Cortical Complexity Changes in Normal Aging and Alzheimer's Disease

正常衰老和阿尔茨海默病中皮质复杂性的变化

• 批准号: 8526326
• 负责人: RICHARD DANIEL KING
• 金额: $ 13.43万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8526326
• 关键词: Accounting; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Anemia; Atlases; Atrophic; Biological Markers; Brain; Cerebral cortex; Cerebrospinal Fluid; Cerebrovascular Disorders; Cerebrum; Classification; Clinic; Clinical; Cognition Disorders; Cognitive; Cognitive aging; Comorbidity; Complex; Computer Analysis; Computer software; Data; Databases; Diabetes Mellitus; Diabetic Angiopathies; Dimensions; Disease; Doctor of Philosophy; Drops; Elderly; Enrollment; Epidemiologic Factors; Epidemiology; Evaluation; Exclusion Criteria; Fellowship; Foundations; Fractals; Goals; Human; Hypertension; Image; Image Analysis; Impaired cognition; Individual; Instruction; K-Series Research Career Programs; Leadership; Learning; Longevity; Magnetic Resonance; Magnetic Resonance Imaging; Measures; Medical; Mental Depression; Mentors; Mentorship; Methodology; Methods; Metric; Neurodegenerative Disorders; Neurology; Outcome; Patients; Pattern; Physicians; Population; Randomized; Recruitment Activity; Research; Research Project Grants; Residencies; Risk Factors; Role; Scanning; Scientist; Sensitivity and Specificity; Shapes; Techniques; Thyroid Diseases; Training; Training Programs; Translating; Validation; Weight; Work; Writing; age effect; aged; aging brain; base; brain shape; burden of illness; career; clinical practice; clinically relevant; cognitive neuroscience; computational neuroscience; computer science; experience; healthy aging; improved; knowledge base; mild cognitive impairment; neuroimaging; neuropsychological; normal aging; novel; older patient; patient oriented research; prospective; research clinical testing; research study; skills; software development; statistics; three-dimensional modeling; tool

DESCRIPTION (provided by applicant): This revised Beeson Patient-Oriented Research Career Development Award (K23) project will provide the mentorship, didactic coursework and individualized instruction to develop Richard D. King, MD, PhD, into a leader in geriatric research. This will build upon his graduate work in computational neuroscience, and his expertise in the disorders of the aging brain derived from his residency and fellowship training in neurology. Dr. King's training goals include 1) building expertise in technical and computational aspects of neuroimaging analysis software development, 2) gaining proficiency with methods of cognitive neuroscience in the geriatric population, 3) learning how to manage complex epidemiologic factors common in elderly patients, and 4) developing proficiency with translating novel imaging analysis tools into clinical practice. Through the training program and research plan outlined in this application, Dr. King will acquire the broad expertise and knowledge base needed to become and independent physician-scientist with a focus on cognitive disorder of elderly subjects. The proposed research is to develop a new structural imaging analysis technique based upon a quantitative metric known as fractal dimension (f3D). There are several novel aspects to this approach. First, f3D is perfectly suited to detect shape changes that occur with atrophy of the human cerebral cortex. Secondly, f3D is a quantitative measure of shape which provides a more robust evaluation than the current standard of qualitative subjective assessments (i.e. "mild" or "moderate" atrophy). Thirdly, f3D integrates information over a range of spatial scales. Dr. King has written software to compute f3D using 3D models of the cortex extracted from high-contrast magnetic resonance (MR) images. It is essential to understand the extent and distribution of size and shape changes occurring with healthy aging because many of these changes are not associated with cognitive dysfunction. With the guidance of mentors expert in cognitive aging, computer science and statistics, Dr. King will create a normative statistical imaging atlas of healthy brain aging using MR images of healthy subjects from two databases. The age-weighted normative atlas will then be used to statistically quantify the effects of neurodegenerative disease on cortical f3D values using MR images of subjects with mild cognitive impairment and mild Alzheimer's disease. Finally, to understand how this imaging approach may be used in clinical practice, it is important to move beyond studies that use highly-selected clinical populations. Dr. King will perform the cortical f3D analysis using prospective imaging data from patients with cognitive complaints seeking clinical evaluation. The data will enable a prospective trial on the role of cortical f3D in clinical practice.

描述（由申请人提供）：这个修订后的比森以患者为导向的研究职业发展奖（K23）项目将提供导师，教学课程和个性化的指导，以发展理查德D。金博士，医学博士，成为老年医学研究的领导者。这将建立在他在计算神经科学的研究生工作，以及他在神经病学的住院医师和奖学金培训中获得的衰老大脑疾病方面的专业知识基础上。金博士的培训目标包括：1）建立神经影像分析软件开发的技术和计算方面的专业知识，2）熟练掌握老年人群的认知神经科学方法，3）学习如何管理老年患者常见的复杂流行病学因素，以及4）熟练掌握将新型成像分析工具转化为临床实践。通过本申请中概述的培训计划和研究计划，金博士将获得成为独立的医生-科学家所需的广泛专业知识和知识基础，重点关注老年受试者的认知障碍。提出的研究是开发一种新的结构成像分析技术的基础上称为分形维数（f3D）的定量度量。这种方法有几个新颖的方面。首先，f3D非常适合检测人类大脑皮层萎缩时发生的形状变化。其次，f3D是形状的定量测量，其提供比当前定性主观评估标准（即"轻度"或"中度"萎缩）更稳健的评估。第三，f3D整合了一系列空间尺度上的信息。King博士编写了软件，使用从高对比度磁共振（MR）图像中提取的皮质3D模型来计算f3D。了解健康老龄化发生的大小和形状变化的程度和分布是至关重要的，因为这些变化中的许多与认知功能障碍无关。在认知老化、计算机科学和统计学专家导师的指导下，King博士将使用来自两个数据库的健康受试者的MR图像创建健康大脑老化的规范统计成像图谱。然后，使用轻度认知障碍和轻度阿尔茨海默病受试者的MR图像，使用年龄加权标准图谱对神经退行性疾病对皮质f3D值的影响进行统计学量化。最后，为了了解这种成像方法如何用于临床实践，重要的是要超越使用高度选择的临床人群的研究。King博士将使用寻求临床评价的认知主诉患者的前瞻性成像数据进行皮质f3D分析。这些数据将使皮质f3D在临床实践中的作用的前瞻性试验。