LOSS OF MEMORY AND HIPPOCAMPAL VOLUME IN AT RISK SUBJECTS

拟议研究的目的是获得更多关于 阿尔茨海默病病程早期的功能和解剖变化 疾病(AD)。这类研究的障碍之一是难以 在受损前识别极早期阿尔茨海默病患者 变得具有临床意义。这里采取的方法是招聘一名 一组被认为有患AD风险的非痴呆症受试者 根据年龄和AD的阳性病史获得一个或多个一级学位 亲戚。60个家族史阴性(FH-)和40个匹配的家庭 痴呆评分正常的病史阳性(FH+)受试者 ADRC将遵循量表的核心神经心理学 电池；每年将用高分辨率核磁共振进行检查 协议。将使用形态测量分析来估计体积 内侧颞叶(MTL)结构、颞叶新皮质和 前额叶新皮质。因为实质体积的丧失常常伴随着 通过增加相邻脑脊液间隙的体积，有可能使周围脑脊液- 海马液容量是MTL丢失的一个更敏感的指标 剩余组织的体积。因此， 内侧颞叶结构周围的裂隙和沟将 也是被测量的。 指导研究设计的模式可概括为：在 该病发病后最早几年，AD的特点是 内侧颞叶结构快速退变，更多的是渐变 新皮质联合区域的变性。在这一阶段， 疾病，记忆障碍是相对孤立的，主要表现为 在最近研究的和未研究的区分能力的下降中 项目，并且越来越倾向于免费犯下入侵错误 召回。在疾病的后期，临床上 严重的痴呆症与退化率的增加不谋而合 在新皮质联合区域。基于此模型，以下是 提出了主要假设： 1.有AD家族史的非痴呆受试者将显示 5年来内侧颞叶结构的损失，相对于 匹配无家族史的AD受试者。 2.此外，FH+受试者随时间的MTL损失将是 明显大于新皮质区域的损失。 3.研究期间的MTL损失将具体涉及 记忆功能的敏感指标表现恶化。

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.