STRUCTURAL CORRELATES IN EARLY AND LATE ONSET ALZHEIMER?S DISEASE

早发型和晚发型阿尔茨海默病的结构相关性

• 批准号: 7369447
• 负责人: MICHELA PIEVANI
• 金额: $ 0.51万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7369447
• 关键词: STRUCTURAL; CORRELATES; EARLY; LATE; ONSET

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Patients with Alzheimer's disease (AD) and symptom onset after 65 years (late onset AD, LOAD) usually show symptoms indicative of medial temporal dysfunction (memory deficits), while patients with AD and symptom onset before 65 years (early onset AD, EOAD) usually show symptoms indicative of neocortical dysfunction (aphasia, apraxia, and visuospatial deficits). Our objective is to identify patterns of atrophy in EOAD and LOAD patients with cortical pattern matching (CPM) algorithms and hippocampal radial mapping (HRM). Methods: High-resolution 3D MR images of EOAD and LOAD patients of similar clinical severity are compared to those of age- and sex-matched controls. CPM is used to identify regions where the cortical gray matter density differs in cases vs controls, and HRM to assess hippocampal volumes difference. MR images are normalized to a customized template using a 12 parameter linear transformation and 3D cortical surfaces of both hemispheres are extracted; 29 sulci are manually outlined on the lateral and medial surface of each hemisphere, and additional 3D lines are drawn to delimit interhemispheric gyral limits. A population specific templates is created averaging the traced sulci among subjects, and the sulci are used as landmarks to warp each subject's anatomy to the template. Original MR images are segmented into gray matter, white matter, and CSF, and the warping fields obtained with cortical pattern matching is applied to the GM images, thus allowing measurement of GM at homologous cortical locations. The mean gray matter proportion is computed for each subject, and statistical significance maps showing correlation between gray matter density and group or cognitive performances (measured with MMSE and neuropsychological tests) will be computed. The hippocampal formation will be isolated by manually tracing on 35 coronal slices the outlines of the hippocampus proper and subiculum after registration of original MRI to stereotactic space; a medial curve will be automatically defined as the 3D curve traced out by the centroid of the hippocampal boundary in each image slice. The radial size of each hippocampus at each boundary point will be assessed by automatically measuring the radial 3D distance from the surface points to the medial curve defined for individual¿s hippocampal surface model. Shorter radial distances will be used as an index of atrophy; statistical maps will be generated indicating local group differences in radial hippocampal distance. Results. Preliminary data show significant gray matter deficits in neocortical temporoparietal, retrosplenial regions and in the frontal lobe for EOAD subjects; LOAD subjects are significantly atrophic mainly in the medial temporal region, with deficits of lesser magnitude in retrospenial areas. Further analysis will be carried out to assess the linkage between gray matter deficits and neuropsychological scores, and between hippocampal volumes and groups.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。背景：阿尔茨海默病(AD)患者在65岁后出现症状(晚发性AD，LOAD)通常表现出内侧颞叶功能障碍(记忆障碍)的症状，而65岁之前出现症状(早发性AD，EOAD)的患者通常出现新皮质功能障碍(失语、失用和视觉空间障碍)的症状。我们的目标是用皮质模式匹配(CPM)算法和海马径向标测(HRM)识别EOAD和LOAD患者的萎缩模式。方法：将临床严重程度相似的Eoad和LOAD患者的高分辨率3D MR图像与年龄和性别匹配的对照组进行比较。CPM用于识别病例与对照组皮质灰质密度不同的区域，HRM用于评估海马体积的差异。使用12参数线性变换将MR图像归一化到定制模板，并提取两个半球的3D皮质表面；在每个半球的外侧和内侧表面手动勾画29个脑沟，并绘制额外的3D线以划定大脑半球间回的界限。创建群体特定模板，该模板平均受试者之间的轨迹沟，并且该沟被用作地标以将每个受试者的解剖扭曲到该模板。原始MR图像被分割为灰质、白质和脑脊液，通过皮质模式匹配获得的翘曲场被应用于GM图像，从而允许在相应的皮质位置测量GM。计算每个受试者的平均灰质比例，并计算显示灰质密度与群体或认知表现(用MMSE和神经心理测试测量)之间的相关性的统计显著图。在将原始MRI配准到立体定向空间后，通过在35个冠状切片上手动跟踪海马体和下丘脑的轮廓来分离海马结构；内侧曲线将自动定义为每个图像切片中由海马区边界质心绘制的3D曲线。通过自动测量从表面点到为单个S海马体表面模型定义的内侧曲线的径向3D距离，将评估每个边界点上每个海马体的径向大小。较短的径向距离将被用作萎缩的指标；将生成统计地图，表明径向海马区距离的局部组差异。结果。初步数据显示，EoAD受试者在新皮质、顶叶、脾后区域和额叶有明显的灰质缺陷；负荷受试者显著萎缩，主要在内侧颞区，在脾后区域的缺陷程度较小。将进行进一步的分析，以评估灰质缺陷和神经心理评分之间的联系，以及海马体体积和组之间的联系。