Functional MRI and Alzheimer's Disease

描述(由申请人提供)：这个项目的总体目标是获得60至75岁的老年受试者海马体(以及边缘系统中的相关结构，如扣带皮质)记忆激活的准确统计图谱。我们的目标的成功完成可能会导致一种基于功能磁共振成像的记忆损伤诊断测试，以表征阿尔茨海默病(AD)高危人群的异常记忆功能。AD的特点是记忆力减退，并伴有病变，尤其是在颞叶和海马区。本申请寻求扩展以前的研究，以产生海马区和扣带回皮质激活的强大地图。使用局部典型相关分析(CCA)，这是一种使用局部自适应空间滤波核的强大的多变量统计方法，可以比单变量方法更可靠地检测海马区的激活。目前的建议是朝着表征记忆功能迈出的第一步，特别是对于有患AD和其他形式痴呆症的风险的人。它分为两个主要阶段，将应用于两个受试组(认知正常受试者和轻度遗忘性认知障碍受试者)。在第一阶段(第一年，方法开发)，将优化两个存储范例。这一阶段的目标是建立一种一致的功能磁共振成像方法(范式和分析方法)，提供通过自适应CCA(CCA的改进版本)测量的可靠的海马区激活结果。在STesIa对10名健康对照受试者进行数据收集和fMRI分析。还将测量扣带回皮质的激活情况。在第二阶段(第二年，临床应用)将对40名受试者进行扫描：20名正常受试者和20名轻度认知障碍患者。将测量海马体和边缘系统的其他区域(如扣带皮质)的激活情况。自适应CCA的性能将与使用SPM2的标准单变量分析进行比较。我们首先将重点放在群体分析上(即调查每组之间记忆激活的差异)，但在后面的阶段，我们将探索个体标记并提供个体可信区间来表征记忆缺陷，这可能预测痴呆症的未来发展。

DESCRIPTION (provided by applicant): The overall goal of this project is to obtain an accurate statistical map of memory activation in the hippocampus (and associated structures in the limbic system such as cingulate cortex) in older subjects, age 60 to 75. The successful completion of our objectives may lead to an fMRI-based diagnostic test for memory impairment to characterize abnormal memory function in people at risk for Alzheimer's disease (AD). AD is characterized by memory loss with pathological changes especially in the temporal lobes and hippocampus. The present application seeks to expand on previous studies to produce robust maps of hippocampal and cingulate cortex activation. Using local Canonical Correlation Analysis (CCA), a powerful multivariate statistical method that uses locally adaptive spatial filter kernels, it is possible to detect activation in the hippocampus more reliably than with univariate methods. The present proposal represents a first step toward characterizing memory function, especially for people at risk for developing AD and other forms of dementia. It is divided into two major phases and will be applied to two subject groups (cognitively normal subjects and subjects with mild amnestic cognitive impairment (MCI)). In phase I (year 1, method development), two memory paradigms will be optimized. The goal in this phase is to establish a consistent fMRI methodology (paradigm and analysis method) providing reliable results of hippocampal activation as measured by adaptive CCA (an improved version of CCA). Data collection and fMRI analysis will be carried out at STesIa for 10 healthy control subjects. Activation in the cingulate cortex will also be measured. In phase II (year 2, clinical application) 40 subjects will be scanned: 20 normal subjects and 20 with mild cognitive impairment. Activations of the Hippocampus and other areas of the limbic system (such as cingulate cortex) will be measured. The performance of adaptive CCA will be compared with a standard univariate analysis using SPM2. We will focus initially on group analysis (i.e., investigating differences in memory activation between each group), but in the later phase we will explore individual markers and provide individual confidence intervals to characterize memory deficit, which might predict future development of dementia.