Project 1: The relationship between Neuropsychological Testing and MRI, PET, and

项目摘要/摘要 包括阿尔茨海默氏症(AD)和帕金森氏病(PD)在内的神经退行性疾病令人痛苦 这对受影响的人及其亲人的生活条件造成了极大的影响，对公共卫生资金构成了越来越大的负担。 随着人口老龄化，这些疾病正变得越来越普遍。神经心理衰退是 是早期阿尔茨海默病的特征，在帕金森病中很常见。这样的症状被识别和跟踪 神经心理测试，这在测试新药方面也很重要。最近的突破导致了 以进一步了解AD和PD的潜在神经生物学，但这些新发现如何与 神经心理测试在很大程度上是未知的。这个项目将为我们提供关于 神经心理测试与阿尔茨海默病和帕金森病新的神经影像和遗传生物标记物的关系。在公元后， 我们将使用功能磁共振成像(FMRI)研究静止的大脑，并了解 大脑网络的连通性与神经心理测试有关。我们还将使用一种新颖的改编 传统上用于啮齿动物研究的任务--莫里斯水迷宫，并在以下背景下理解这一点 在功能磁共振成像过程中保持静态连接。该项目的其他方面将涉及AD和PD：我们将使用一种 方法评估大脑中的炎症，并了解局部炎症如何与不同的 认知障碍的类型。我们还将发现炎症和AD风险的遗传生物标记物 与神经心理学有关。通过更好地理解神经心理学和这些 我们将能够为这两套技术的解释提供新的生物标记物。神经心理学是 目前是监测在这两种疾病中测试的新药的核心，并了解 我们的发现背后的神经生物学过程将是促进新的 药物。本项目建议书中概述的研究将产生初步数据，以进一步回答 关于这些疾病的神经心理学的问题。与详细的指导计划相结合， 这里提出的研究和获得的经验如果得到资助，将使项目负责人成为一个有竞争力的人 独立研究基金的候选人。

PROJECT SUMMARY/ABSTRACT Neurodegenerative diseases including Alzheimer's (AD) and Parkinson's disease (PD) are distressing conditions for those affected and their loved ones, and represent a growing burden on public health funds. These diseases are becoming increasingly prevalent as the population ages. Neuropsychological decline is the hallmark of early AD, and is common in PD. Such symptoms are identified and tracked with neuropsychological tests, which are also important in testing new medications. Recent breakthroughs have led to further understanding of the underlying neurobiology of AD and PD, but how these new findings relate to neuropsychological testing is largely unknown. This project will inform our interpretation of neuropsychological testing in relation to novel neuroimaging and genetic biomarkers of AD and PD. In AD, we will we will study the brain at rest using functional magnetic resonance imaging (fMRI), and learn how the connectivity of the brain's networks relate to neuropsychological testing. We will also use a novel adaptation of a task traditionally used in rodent studies, the Morris Water Maze, and understand this in the context of connectivity at rest during fMRI. Other aspects of the project will involve both AD and PD: we will use a novel method to assess inflammation in the brain, and understand how regional inflammation relates to different types of cognitive impairment. We will also discover how genetic biomarkers of inflammation and AD risk relate to neuropsychology. By gaining better understanding of the correlations of neuropsychology and these novel biomarkers we will be able to inform interpretation of both sets of techniques. Neuropsychology is currently central to the monitoring of novel medications being tested in both diseases, and understanding the neurobiological processes underlying our findings will be central in contributing to the development of new medications. The studies outlined in this project proposal will generate preliminary data to answer further questions about the neuropsychology of these diseases. In combination with a detailed mentoring scheme, the studies proposed here and the experience gained if funded will result in the project leader being a competitive candidate for independent research funding.