DEMENTIA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这个神经成像（NI）项目的主要目标是利用高场磁共振成像和光谱技术确定记忆衰退的大脑相关因素和未来衰退的预测因素。研究参与者是从爱因斯坦衰老研究（EAS）中招募的。具体的神经成像数据包括脑体积的测量（灰质、白质和心室系统体积的估计）和海马的体积测量，海马是一个已知与记忆有关的区域（0.75x1.0x1.5mm = 1.125mm3像素分辨率）。此外，磁共振光谱用于测量海马内神经细胞的代谢活动。我们假设，在轻度记忆衰退和痴呆症临床前发病期间，神经细胞代谢在神经细胞丢失之前发生了变化；如果这是正确的，我们预测神经代谢（由海马n -乙酰天冬氨酸（NAA）浓度比测量）会在体积测量下降之前发生变化。这些测量NAA和NAA/肌酸（NAA/CR）比值已应用于癫痫、多发性硬化症、中风、肌萎缩侧索硬化症和阿尔茨海默病，以定位疾病并提供疾病严重程度和体积的指标。在这项研究中，我们使用体积和代谢成像来评估具有中度认知障碍状态的个体的大脑结构和功能，预测AD和混合性痴呆-遗忘性认知障碍（ACI）以及匹配的对照。我们确实对非遗忘性认知障碍（NonACI）患者进行了成像，以将资源集中在更有希望的高风险人群上。成像测量将用于预测认知正常个体中这些中间状态的发展，以及预测正常受试者中AD和混合性痴呆的发展。我们已经完成了4种初步研究：1。6名患有急性脑损伤的老年爱因斯坦衰老研究受试者、4名无急性脑损伤的老年对照受试者和10名年轻人的海马MRS数据。虽然在老年组中没有足够的力量来证明年轻人和老年人之间的半球差异，但结合左海马和右海马的数据足以在该组中发现老年人和年轻人对照之间的显著差异。2. 老年EAS受试者光谱与认知测量的相关性。我们发现，左海马的光谱数据与言语记忆相关（R=0.75, p0.015）。正如预测的那样，对右侧海马体的评估发现与类别流畅性没有显著的关系。右侧海马光谱数据与Blessed评分相关（R=0.70, p0.025）。在这一小群受试者志愿者中，没有发现表现和海马体积之间的显著关系。3. 17个对照组的数据显示全脑组织分割。脑总容量和灰质分数体积（GM/(CSF+GM+WM)）与已发表的数据一致（Ge et al 2002，综合性别，50岁以下，灰质分数52.5%）。女性（n=7）的总脑容量为1.27'b10.14升，男性（n=10）的总脑容量为1.41'b10.15升。脑灰质体积分数为1.27'b10.14，男性（n=10）为1.41'b10.15升。灰质体积分数随年龄的增长呈线性下降（R=0.51, p.04）。4. 我们光谱数据的再现性。再现性是任何磁共振成像和光谱研究的一个重要问题。特别是海马体，是一个具有显著结构变异性的区域。为了评估光谱研究的可重复性，我们从4名志愿者的海马体和整个大脑中获得了重复的数据集（所有数据集都是在不同的日子获得的，间隔最多5个月）。根据NAA/Cr测量、海马和全脑容量测量的稳定性分析数据。目前数据的重现性约为10%。与其他重复性研究相比，这一结果很好，这些研究发现了10%至22%的值（Maton等人，Chard等人）。尽管如此，考虑到这种测量在海马体中的重要性，我们将通过实施体素转移方法来改进采集和分析。研究期间未发生不良反应。3名受试者因幽闭恐惧症（n= 2）或其他原因（n= 1）未参加影像学检查。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The primary objective of this neuroimaging (NI) project is to identify brain correlates of memory decline and predictors of future decline using high field MR imaging and spectroscopy. Study participants were recruited from the Einstein Aging Study (EAS). Specific neuroimaging data included measurement of brain volume (estimates of gray-matter, white-matter, and ventricular system volumes) and volumetric measurements of the hippocampus, a region known to be involved in memory (0.75x1.0x1.5mm = 1.125mm3 pixel resolution). In addition, MR spectroscopy is used to measure the metabolic activity of nerve cells within the hippocampus. We hypothesized that during mild memory decline and during the preclinical onset of dementia nerve cell metabolism changes before nerve cells are lost; if this is correct, we predicted that nerve metabolism (as measured by hippocampal N-acetylaspartate (NAA) concentration ratio would change before volumetric measures decline. These measurements of NAA and the NAA /Creatine (NAA/CR) ratio have been applied in epilepsy, multiple sclerosis, stroke, amyotrophic lateral sclerosis and Alzheimer disease to localize disease and to provide an index of disease severity and volume. In this study we use volumetric and metabolic imaging to assess brain structure and function in individuals with an intermediate state of cognitive impairment that predicts AD and mixed dementia - Amnestic Cognitive Impairment (ACI) as well as matched controls. We did image individuals with Non-Amnestic Cognitive (NonACI) Impairment as proposed to focus resources on the more promising high risk group. Imaging measures will be used to predict the development of these intermediate states in cognitively normal individuals as well as to predict the development of AD and mixed dementia in normal subjects. We have completed 4 kinds of preliminary studies: 1. Hippocampal MRS data from 6 elderly Einstein Aging Study subjects with ACI, 4 elderly control subjects without ACI and 10 young adults. Although there is not sufficient power in the aged group to demonstrate a hemispheric difference between young and aged groups, combining the left and right hippocampal data is sufficient in this group to detect a significant difference between the aged and younger adult controls. 2. Correlations between spectroscopic and cognitive measures among elderly EAS subjects. We found in that spectral data from the left hippocampus was correlated with verbal memory (R=0.75, p0.015). As predicted, assessment of the right hippocampus found no significant relationship with category fluency. Right hippocampal spectral data correlated with the Blessed score (R=0.70, p0.025). With this small group of subject volunteers, no significant relationship was detected between performance and hippocampal volumetry. 3. Data on 17 control subjects demonstrating whole brain tissue segmentation. Both the total brain volume and the fractional gray matter volumes (GM/(CSF+GM+WM)) are in agreement with published values (Ge et al 2002, combined genders, under 50 years of age, 52.5% fraction gray). For women (n=7) the total brain volume was 1.27'b10.14, for men (n=10) this was 1.41'b10.15 liters. The fraction gray matter volume was 1.27'b10.14, for men (n=10) this was 1.41'b10.15 liters. The fraction of gray matter volume linearly decreases with age (R=0.51, p.04). 4. Data reproducibility of our spectroscopic data. Reproducibility is an important concern of any MR imaging and spectroscopic study. The hippocampus, in particular, is a region of significant structural variability. To assess the reproducibility of the spectroscopic study, we acquired repeated datasets (all acquired on separate days, up to 5 months apart) from four volunteers through the hippocampus and whole brain. Data were analyzed in terms of stability of the NAA/Cr measurement, hippocampal and whole brain volumetry. The reproducibility of the present data is approximately 10%. This compares well to other studies of reproducibility, which have found values of 10 to 22% (Maton et al, Chard et al). Nonetheless, given the importance of such measurements in the hippocampus, we will be improving the acquisition and analysis through implementation of voxel shifting methods. During the studies there were no adverse reactions. Three subjects were scheduled for imaging but did not participate because of claustrophobia (n= 2) or other reasons (n= 1).