Clinical, Radiographic, and Genetic Associations in Cerebral Amyloid Angiopathy

脑淀粉样血管病的临床、放射学和遗传关联

• 批准号: 7281748
• 负责人: Steven M Greenberg
• 金额: $ 18.14万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7281748
• 关键词: Affect; Age-associated memory impairment; Anatomy; Area; Arterioloscleroses; Arts; Biochemical Genetics; Biometry; Blood Vessels; Brain hemorrhage; Cerebral Amyloid Angiopathy; Cerebral hemisphere hemorrhage; Characteristics; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Cognition; Cognitive; Collaborations; Computer Assisted; Cross-Sectional Studies; Data; Diagnostic; Diffusion; Elderly; Environment; Functional disorder; Funding; Future; Gait; Generations; Hand; Hemorrhage; Human; Human Genetics; Image; Image Analysis; Impaired cognition; Impairment; Investigation; Lesion; Longitudinal Studies; MRI Scans; Medical; Mentors; Methods; Modality; Molecular; Nervous System Physiology; Neurologic; Neurologic Dysfunctions; Outcome; Pathology; Patients; Pattern; Population; Population Genetics; Populations at Risk; Prevention; Publications; Research; Research Personnel; Research Training; Resolution; Risk Factors; Stroke; Training; Training Programs; base; bioimaging; career; clinical Diagnosis; cohort; depressive symptoms; genetic analysis; genetic association; medical schools; multidisciplinary; patient oriented research; prevent; programs; prospective; skills; spatial relationship; success; synergism; tool; treatment trial; white matter; white matter change; white matter damage

DESCRIPTION (provided by applicant): There is no known treatment for cerebral amyloid angiopathy (CAA), an important cause of hemorrhagic stroke and increasingly recognized contributor to vascular cognitive impairment and neurological dysfunction. We propose to use our prospective longitudinal study of patients with CAA-related intracerebral hemorrhage as the centerpiece of both a multidisciplinary investigation of the mechanisms by which CAA affects neurological function and a clinical research training program for early investigators in the fields of stroke and vascular cognitive impairment. Building on the Principle's Investigator's groundbreaking success in defining the diagnosis, clinical course, and pathophysiology of CAA, the proposed studies focus on 1) the interrelationship between CAA-related hemorrhages and white matter lesions, 2) the effects of these lesions on cognition, depressive symptoms, functional skills, and gait, and 3) their association with genetic and biochemical risk factors. Successful completion of these studies will represent a key step towards developing diagnostic markers, outcome markers, and candidate treatments for future trials aimed at prevention of CAA-related hemorrhage and cognitive dysfunction. The studies will be performed as part of long-standing collaborations with investigators (drawn from the rich Harvard Medical School research environment) at the Martinos Center for Biomedical Imaging (Dr. A. Gregory Sorensen, Co-Director), Program in Medical and Population Genetics (Dr. David Altschuler, Director), and Biostatistics Center (Dr. Rebecca Betensky). The multidisciplinary team of collaborators will also serve as the basis for an intensive patient-oriented research training program in key aspects of neurological research, including principles of patient-oriented research, neurological and cognitive assessment of intracerebral hemorrhage subjects, computer-assisted radiographic image analysis, human genetic analysis, and biostatistics. The Principle Investigator has an outstanding record of mentoring early clinical investigators, demonstrated by trainees' success in publication, research funding, and transition to independent careers. The Principle Investigator's consistent success in defining biologically based approaches to compelling research questions and obtaining NIH-funded R01 support make it extremely likely that the proposed studies will succeed both as cutting-edge clinical investigation and tools for training a new generation of stroke investigators.

描述（由申请人提供）：脑淀粉样血管病（CAA）尚无已知的治疗方法，CAA 是出血性中风的重要原因，并且越来越被认为是导致血管性认知障碍和神经功能障碍的原因。我们建议将我们对 CAA 相关脑出血患者的前瞻性纵向研究作为 CAA 影响神经功能机制的多学科研究和中风和血管认知领域早期研究人员临床研究培训计划的核心损害。基于原则研究者在定义 CAA 的诊断、临床病程和病理生理学方面取得的突破性成功，拟议的研究重点关注 1) CAA 相关出血和白质病变之间的相互关系，2) 这些病变对认知、抑郁的影响症状、功能技能和步态，3) 它们与遗传和生化危险因素的关联。这些研究的成功完成将代表着为未来旨在预防 CAA 相关出血和认知功能障碍的试验开发诊断标记物、结果标记物和候选治疗方法迈出了关键一步。这些研究将作为与马蒂诺斯生物医学成像中心（联合主任 A. Gregory Sorensen 博士）医学和人口项目的研究人员（来自哈佛医学院丰富的研究环境）的长期合作的一部分进行遗传学（David Altschuler 博士，主任）和生物统计中心（Rebecca Betensky 博士）。多学科合作者团队还将作为神经学研究关键方面以患者为中心的强化研究培训计划的基础，包括以患者为中心的研究原则、脑出血受试者的神经和认知评估、计算机辅助放射线图像分析、人类遗传分析和生物统计学。首席研究员在指导早期临床研究人员方面拥有出色的记录，学员在发表文章、研究资助和向独立职业过渡方面的成功证明了这一点。首席研究员在定义基于生物学的方法来解决引人注目的研究问题并获得 NIH 资助的 R01 支持方面取得了持续成功，这使得拟议的研究极有可能作为尖端临床研究和培训新一代中风研究人员的工具而取得成功。