PATHOPHYSIOLOGY/FUNCTIONAL SIGNIFICANCE OF WHITE MATTER SIGNAL HYPERINTENSITIES

这项多学科前瞻性纵向研究的目标 旨在阐明白血球的病理生理和功能意义 物质信号高强度(WMSH)，一种在 正常和痴呆老年人的脑MRI检查。两人的证据 我们将研究不同的病理生理模型：1)WMSH是由 通过慢性深部白质低灌流与2)WMSH代表 原发神经元或轴突引起的继发性脱髓鞘 损失。一种新的视觉-触觉运动反应时范式 开发专门用于测试功能的神经解剖学模型 WMSH的意义：即WMSH导致反应减慢 需要在分布式网络中集成感觉模式。 四组每组32名受试者(n=128)将使用纵向研究 重复测量设计。两个主要的子组由Normal组成 老年人(CDR 0)和认知障碍患者(CDR 0.5， 1或2)。根据疾病的严重程度进一步划分每个亚组 WMSH(轻度与中度或重度)。在基线上，实验反应 时间范式，以及对WMSH和灰质的体积研究 对所有受试者都适用。脑血流量、葡萄糖代谢 在WMSH地区将使用共同登记的位置发射获得 部分轻、重度患者的断层扫描(PET)和磁共振成像(MRI) WMSH严重程度。核磁共振研究、反应时间测试和正电子发射计算机断层扫描 每隔18个月重复。白色的区域定量研究 将进行物质检查，以测试脱髓鞘的模式 与血管灌注或神经元的模式更符合 退化。 根据选择性脆弱性的区域模式，我们预计 患有轻度和中度AD的患者以及VAD患者将能够 执行视觉-触觉运动范例。已经进行了纵向设计 选择来阐明大脑萎缩之间的时间关系 血流和新陈代谢以及控制个体差异 实验变量。因此，这项研究旨在澄清 WMSH在AD和VAD中的临床意义和病理生理意义。

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.