DEMENTIA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项神经成像(NI)项目的主要目标是使用高场磁共振成像和光谱学来识别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老龄化研究(EAS)招募的。具体的神经成像数据包括测量大脑体积(灰质、白质和脑室系统体积的估计)和海马区的体积测量，海马区是已知的与记忆有关的区域(0.75x1.0x1.5 mm=1.125mm3像素分辨率)。此外，磁共振波谱被用来测量海马区神经细胞的代谢活动。我们假设，在轻度记忆减退和痴呆临床前发作期间，神经细胞代谢在神经细胞丢失之前发生变化；如果这是正确的，我们预测神经代谢(由海马体N-乙酰天冬氨酸(NAA)浓度比测量)将在体积测量下降之前发生变化。这些NAA和NAA/肌酸(NAA/CR)比值的测量已被应用于癫痫、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数。 在这项研究中，我们使用体积和代谢成像来评估认知损害中间状态的个体的大脑结构和功能，该状态预测AD和混合性痴呆-遗忘型认知损害(ACI)以及匹配的对照组。我们按照建议将资源集中在更有前途的高危人群上，对患有非遗忘性认知(non-ACI)损害的个体进行了成像。成像方法将被用来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和混合性痴呆症的发展。 我们已经完成了四种初步研究： 1.6例老年爱因斯坦老年组ACI患者、4例非ACI老年对照组和10例青壮年患者的海马区MRS数据。 尽管老年组没有足够的能量来显示青年组和老年组之间的半球差异，但结合左侧和右侧海马区的数据在这一组中足以检测出老年组和年轻人对照组之间的显著差异。 2.老年EAS受试者的光谱测量与认知测量之间的相关性。我们发现左侧海马区的光谱数据与言语记忆相关(R=0.75p&lt；0.015)。正如预测的那样，对右侧海马体的评估发现与类别流利性没有显著关系。右侧海马区频谱数据与BLISED评分相关(R=0.7，p&lt；0.025)。在这一小组受试者志愿者中，没有发现表现和海马体体积测量之间的显著关系。 3.17名对照受试者的数据显示了整个脑组织的分割。脑总体积和灰质分数(Gm/(CSF+Gm+WM))与已发表的值一致(GE等人，2002年，男女混合，50岁以下，灰分52.5%)。女性(n=7)的总脑体积为1.27‘b10.14，男性(n=10)为1.41’b10.15升。灰质体积分数为1.27‘b10.14，男性为1.41’b10.15升。灰质体积分数随年龄增长呈线性下降(R=0.51，p&lt；0.04)。 4.光谱数据的数据再现性。重复性是任何磁共振成像和光谱研究的一个重要问题。尤其是海马体，是一个具有显著结构变异性的区域。为了评估光谱研究的重复性，我们通过海马体和整个大脑从四名志愿者那里获得了重复的数据集(都是在不同的日期获取的，间隔长达5个月)。从NAA/Cr测量、海马区和全脑体积测量的稳定性方面对数据进行分析。目前数据的再现性约为10%。这与其他重复性研究相比要好得多，后者发现重复性的价值在10%到22%之间(Maton等人，Chard等人)。尽管如此，鉴于这种测量在海马体中的重要性，我们将通过实施体素移位方法来改进采集和分析。 在研究期间，没有出现不良反应。3名受试者因幽闭恐惧症(n=2)或其他原因(n=1)而没有参与。

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, p<0.015). 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, p<0.025). 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).