PATHOPHYSIOLOGY/FUNCTIONAL SIGNIFICANCE OF WHITE MATTER SIGNAL HYPERINTENSITIES

白质信号高信号的病理生理学/功能意义

• 批准号: 6234504
• 负责人: HELENA Chang CHUI
• 金额: $ 23.27万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-15 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6234504
• 关键词: brain circulation; brain electrical activity; cerebral ischemia /hypoxia; dementia; human old age (65+); human subject; longitudinal human study; magnetic resonance imaging; neural degeneration; neural transmission; neuropsychological tests; positron emission tomography; psychomotor reaction time

The objective of this multi-disciplinary prospective longitudinal study is to elucidate the pathophysiologic and functional significance of white matter signal hyperintensities (WMSH), a highly prevalent funding in brain MRI of normal and demented elderly persons. Evidence for two alternative pathophysiologic models will be examined: 1) WMSH are caused by chronic hypoperfusion of the deep white matter vs. 2) WMSH represent secondary demyelination that results from primary neuronal or axonal loss. A new visual-tactile motor reaction time paradigm has been developed to specifically test a neuroanatomical model for the functional significance of WMSH: namely, that WMSH causes slowing in responses that requires integration of sensory modalities across a distributed network. Four groups of 32 subjects each (n=128) will studied using a longitudinal repeated-measures design. The two major subgroups are comprised of normal elderly persons (CDR 0) and patients with cognitive impairment (CDR 0.5, 1 or 2). Each subgroup is further divided according to the severity of WMSH (mild vs moderate or severe). At baseline, the experimental reaction time paradigm, as well as volumetric studies of WMSH and grey matter will be performed for all subjects. Cerebral blood flow, glucose metabolism in areas of WMSH will be obtained using coregistered position emission tomography (PET) and MRI for a subset of patients with mild or severe WMSH severity. MRI studies, reaction time testing and PET will be repeated after 18 month intervals. Regional quantitative studies of white matter will be performed to test whether the pattern of demyelination corresponds better with the pattern of vascular perfusion or neuronal degeneration. Based upon regional patterns of selective vulnerability, we anticipate that patients with mild so moderate AD, as well as VaD, will be able to perform the visual-tactile motor paradigm. A longitudinal design has been chosen to clarify the temporal relationship between diminished cerebral blood flow and metabolism and to control for individual differences in the experimental variables. Thus, this study is designed to clarify the clinical importance and pathophysiology of WMSH in both AD and VaD.

这项多学科前瞻性纵向研究的目的 目的是阐明白细胞的病理生理学和功能意义 物质信号高信号（WMSH）是一种非常普遍的资助 正常和痴呆老年人的脑部 MRI。两人的证据 将检查替代的病理生理学模型：1）引起 WMSH 深部白质慢性灌注不足 vs. 2) WMSH 代表 由原发性神经元或轴突引起的继发性脱髓鞘 损失。一种新的视觉-触觉运动反应时间范例 开发用于专门测试功能性神经解剖模型 WMSH 的重要性：即，WMSH 会导致反应减慢， 需要跨分布式网络集成感官模式。 四组，每组 32 名受试者（n = 128）将使用纵向研究 重复测量设计。两个主要亚组由正常人组成 老年人（CDR 0）和认知障碍患者（CDR 0.5， 1 或 2)。每个亚组根据严重程度进一步划分 WMSH（轻度与中度或重度）。在基线时，实验反应 时间范式以及 WMSH 和灰质的体积研究将 对所有科目进行。脑血流量、葡萄糖代谢 WMSH 区域中的值将使用共同配准位置发射获得 部分轻度或重度患者的断层扫描 (PET) 和 MRI WMSH 严重性。 MRI 研究、反应时间测试和 PET 将 间隔 18 个月后重复一次。白人的区域定量研究 将进行测试以测试脱髓鞘模式是否 与血管灌注或神经元的模式更好地对应 退化。 根据选择性脆弱性的区域模式，我们预计 患有轻度至中度 AD 以及 VaD 的患者将能够 执行视觉-触觉运动范例。纵向设计已 选择澄清脑功能减弱之间的时间关系 血流量和新陈代谢，并控制个体差异 实验变量。因此，本研究旨在澄清 WMSH 在 AD 和 VaD 中的临床重要性和病理生理学。