Functional MRI and Alzheimer's Disease

描述（由申请人提供）：该项目的总体目标是获得60至75岁老年受试者海马体（以及边缘系统中相关结构，如扣带皮层）记忆激活的准确统计图。我们的目标的成功完成可能会导致基于fmri的记忆障碍诊断测试，以表征阿尔茨海默病（AD）风险人群的异常记忆功能。阿尔茨海默病的特点是记忆丧失，尤其是颞叶和海马的病理改变。目前的应用程序旨在扩大先前的研究，以产生海马体和扣带皮层激活的强大地图。使用局部典型相关分析（CCA），一种强大的多元统计方法，使用局部自适应空间滤波核，可以比单变量方法更可靠地检测海马体的激活。目前的建议是表征记忆功能的第一步，特别是对于那些有患阿尔茨海默病和其他形式痴呆风险的人。它分为两个主要阶段，将适用于两个受试者群体（认知正常受试者和轻度遗忘性认知障碍（MCI）受试者）。在第一阶段（第一年，方法开发），将优化两种内存范式。本阶段的目标是建立一种一致的fMRI方法（范式和分析方法），提供通过自适应CCA （CCA的改进版本）测量的海马激活的可靠结果。10名健康对照者的数据收集和功能磁共振成像分析将在STesIa进行。扣带皮层的激活也将被测量。在第二阶段（第2年，临床应用），将扫描40名受试者：20名正常受试者和20名轻度认知障碍受试者。海马体和其他边缘系统区域（如扣带皮层）的激活将被测量。将自适应CCA的性能与使用SPM2的标准单变量分析进行比较。我们将首先关注群体分析（即调查各组之间记忆激活的差异），但在后期阶段，我们将探索个体标记物并提供个体置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.