LOSS OF MEMORY AND HIPPOCAMPAL VOLUME IN AT RISK SUBJECTS

高危受试者记忆力和海马体积丧失

• 批准号: 3745701
• 负责人: TERRY L JERNIGAN
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3745701
• 关键词: Alzheimer's disease; dementia; disease /disorder proneness /risk; frontal lobe /cortex; hippocampus; human old age (65+); human subject; image processing; magnetic resonance imaging; memory; neuroanatomy; neuropsychological tests; temporal lobe /cortex

The aim of the proposed study is to gain more information about functional and anatomical changes very early in the course of Alzheimer's Disease (AD). One of the obstacles to such studies is the difficulty of identifying individuals with very early AD before their impairments become clinically significant. The approach taken here is to recruit a group of nondemented subjects considered to be at risk for developing AD by virtue of age and a positive history of AD in one or more first-degree relatives. Sixty family history negative (FH-) and 40 matched family history positive (FH+) subjects with normal scores on dementia rating scales will be followed in the ADRC with the core neuropsychological battery; and will be examined annually with a high-resolution MRI protocol. Morphometric analysis will be employed to estimate the volumes of mesial temporal lobe (MTL) structures, temporal neocortex, and prefrontal neocortex. Since parenchymal volume loss is often accompanied by increased volume of adjacent CSF spaces, it is possible that peri- hippocampal fluid volume will be a more sensitive index of MTL loss than will the volume of the remaining tissue. Therefore, the volume of the fissures and sulci surrounding the mesial temporal lobe structures will also be measured. The model guiding the study design can be summarized as follows: In the earliest years after the onset of the disease, AD is characterized by rapid degeneration in mesial temporal lobe structures, with more gradual degeneration in neocortical association areas. During this stage of the illness, memory impairment is relatively isolated and manifests primarily in a decreasing ability to discriminate recently studied from unstudied items, and in an increasing propensity to make intrusion errors in free recall. In the later stages of the illness, the onset of clinically significant dementia coincides with an increasing rate of degeneration in neocortical association areas. Based on this model, the following primary hypotheses are advanced: 1. Nondemented subjects with a positive family history for AD will show loss in mesial temporal lobe structures, over five years, relative to matched subjects without a family history for AD. 2. Furthermore, the loss over time in the MTL of FH+ subjects will be significantly greater than losses in neocortical regions. 3. MTL losses over the study period will be specifically related to worsening performance on sensitive measures of memory function.

拟议研究的目的是获得更多关于 阿尔茨海默病早期的功能和解剖学变化 疾病（AD）。 这种研究的障碍之一是难以 在他们的损伤之前识别患有非常早期AD的个体 临床意义重大。 这里采取的方法是招募一名 被认为有AD发生风险的非痴呆受试者组 根据年龄和一个或多个一级AD的积极历史， 亲戚 60个家族史阴性（FH-）和40个匹配的家族 痴呆评分正常的病史阳性（FH+）受试者 将在ADRC中使用核心神经心理学量表 电池;并将每年进行一次高分辨率MRI检查 议定书 将采用形态学分析来估计体积 内侧颞叶（MTL）结构，颞叶新皮层， 前额叶新皮层 由于脑实质容量的丧失往往伴随着 通过增加相邻CSF空间的体积，有可能 海马液体体积将是MTL损失的更敏感指标， 将剩余组织的体积。 因此， 内侧颞叶结构周围的裂隙和沟将 也要衡量。 指导研究设计的模型可以总结如下： 在疾病发作后的最早几年，AD的特征在于： 内侧颞叶结构迅速退化， 新皮质联合区的退化。 在这一阶段， 疾病，记忆障碍是相对孤立的，主要表现为 区分最近研究和未研究的能力下降 项目，并在不断增加的倾向，使入侵错误的免费 记得了 在疾病的后期，临床上 严重的痴呆症与退化率的增加相一致 大脑皮层的联系区 基于此模型，以下 提出了主要假设： 1. 具有AD阳性家族史的非痴呆受试者将显示 近中颞叶结构的损失，超过五年，相对于 没有AD家族史的匹配对象。 2. 此外，FH+受试者MTL随时间的损失将是 显著大于新皮层区域的损失。 3. 研究期间的MTL损失将与以下因素具体相关： 在记忆功能的敏感测量上的性能恶化。