Neural Correlates of Cognitive Prodromes in Neurodegenerative Dementias

项目一概要/摘要 早期识别神经退行性疾病中的脯氨酸对于理解神经退行性疾病的发病机制具有重要意义。 进行性认知变化的干预过程和潜力。前驱期阿尔茨海默病可能 表现在多个认知领域，包括记忆或执行缺陷，使其难以区分 从其他前驱期病理生理学，如额颞叶痴呆。本项目解决了这一难题 通过将网络完整性的结构和功能标记与白色物质的新测量相结合， 使用最近开发的NIH人类连接组项目扫描仪。这种最先进的 仪器被开发用于白色物质纤维束完整性的高保真成像，但也允许 常规成像。这些技术优势被项目目标所利用。项目重点是 具有主观认知问题或轻度认知障碍的受试者，表现出主要的 执行功能障碍或主要记忆缺陷。目标1将检验这两种认知 表型将与不同组织中完整性的结构和功能连接性测量相关。 网络.目标2将检验以下假设：使用扩散成像对白色物质完整性进行新的测量， 连接组项目扫描仪将提高对这两种认知功能早期损伤的敏感性， 表型与目标1中开发的结构和功能连接性措施配对时。因为 由于Connectome方法的新奇，我们将评估纤维束识别和完整性的灵敏度 与传统方法相比，在一个受试者子集中进行了3年的随访。 该项目解决了日益增长的需要早期识别和鉴别诊断的个人， 将继续发展不同的神经退行性疾病，以便他们可以有针对性地参与 临床试验或生活方式干预。这些目标的成功实现将有助于新的神经影像学 前驱神经退行性疾病的标志物，并将进一步科学知识的关系， 在功能网络完整性和连接网络内关键节点的纤维束的完整性之间。

PROJECT ONE SUMMARY/ABSTRACT Early identification of prodromes in neurodegenerative diseases is of great importance for understanding the course of and potential for interventions in progressive cognitive change. Prodromal Alzheimer's disease may manifest in multiple cognitive domains, including memory or executive deficits, making it difficult to distinguish from other prodromal pathophysiologies such as frontotemporal dementia. This project addresses this difficulty by combining structural and functional markers of network integrity with novel measures of white matter disruption using the recently developed NIH Human Connectome Project scanner. This state-of-the-art instrument was developed for high fidelity imaging of the integrity of white matter fiber tracts, but also allows conventional imaging. These technical advantages are leveraged by the project aims. The project focus is on subjects with subjective cognitive concerns or mild cognitive impairment exhibiting a phenotype of predominant executive dysfunction or of predominant memory deficits. Aim 1 will test the hypothesis that these two cognitive phenotypes will be associated with structural and functional connectivity measures of the integrity in different networks. Aim 2 will test the hypothesis that novel measures of white matter integrity using diffusion imaging on the Connectome Project scanner will improve sensitivity to early impairments in the these two cognitive phenotypes when paired with the structural and functional connectivity measures developed in Aim 1. Because of the novelty of the Connectome methods, we will assess the sensitivity of fiber tract identification and integrity compared to conventional methods across a 3-year follow-up interval in a subset of subjects. The project addresses a growing need for early identification and differential diagnosis of individuals who will go on to develop different neurodegenerative diseases so that they can be targeted for participation in clinical trials or lifestyle interventions. Successful completion of the aims will contribute novel neuroimaging markers of prodromal neurodegenerative diseases and will further scientific knowledge of the relationship between functional network integrity and the integrity of fiber tracts connecting key nodes within a network.