STRUCTURAL CORRELATES IN EARLY AND LATE ONSET ALZHEIMER'S DISEASE

点击翻译按钮获取中文摘要

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 individuals 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.