Functional MRI and Alzheimer's Disease

描述（由申请人提供）：本项目的总体目标是获得年龄在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，如扣带皮层）中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一个基于fMRI的诊断测试的记忆障碍，以表征异常的记忆功能在阿尔茨海默病（AD）的风险的人。AD的特征是记忆丧失，伴有病理改变，特别是在颞叶和海马。本申请试图扩展先前的研究以产生海马和扣带皮层激活的鲁棒图。使用局部典型相关分析（CCA），一个强大的多变量统计方法，使用局部自适应空间滤波器内核，它是可能的，以检测激活海马比单变量方法更可靠。目前的提议代表了表征记忆功能的第一步，特别是对于有发展AD和其他形式痴呆风险的人。它分为两个主要阶段，并将应用于两个受试者组（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），将优化两种记忆模式。这一阶段的目标是建立一个一致的fMRI方法（范例和分析方法），提供可靠的结果海马激活的自适应CCA（CCA的改进版本）测量。将在STesIa对10名健康对照受试者进行数据收集和fMRI分析。还将测量扣带皮层中的激活。在II期（第2年，临床应用）中，将扫描40例受试者：20例正常受试者和20例轻度认知障碍受试者。将测量海马和边缘系统其他区域（如扣带皮层）的激活。将自适应CCA的性能与使用SPM 2的标准单变量分析进行比较。我们将首先关注组分析（即，研究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.