Assessment of Alzheimer's Disease Risk with Structural and Functional MRI

描述（由申请人提供）：阿尔茨海默病（AD）是美国65岁以上成年人痴呆症的最常见原因（Evans, 1990）。阿尔茨海默病是一种使人衰弱的疾病，对患者、护理人员、家庭和社会都有毁灭性的心理和经济影响。早期发现是成功治疗的关键（Solomon & Murphy, 2005）。早期缺陷通常涉及记忆（Salmon & Bondi, 1999），这是一个重要的研究课题，因为它在AD诊断中必不可少，对功能有重大影响。内侧颞叶（MTL）结构参与将新信息编码到记忆中（Squire, 1992），并被确定为最初受AD神经病理影响的结构（Braak & Braak, 1991; Jack et al., 1992）。轻度认知障碍（Petersen et al., 1999; Tierney et al., 1996）和载脂蛋白E （APOE）的epsilon 4等位基因与AD风险增加有关（Corder et al., 1993）。因此，本提案的长期目标是开发一个使用动脉自旋标记（ASL）磁共振成像（MRI）技术的研究项目，以检查(a)有AD风险的个体在编码过程中MTL亚区的反应，以及(b)制定早期识别这些个体的可靠策略，以便在开发过程中针对这些个体进行治疗。该项目的一个具体目标是使用ASL MRI来扩展其他成像方式的先前发现，并检查非痴呆老年人在休息和记忆编码期间的大脑激活模式。此外，本项目旨在评估非痴呆老年人MTL形态测定。这些具体目标将通过比较结构完整性、大脑反应、认知表现以及这些变量之间的相互作用的组比较方法来实现。这些变量将在有患阿尔茨海默病风险的老年人和没有患阿尔茨海默病风险的老年人之间进行比较。评估学习、记忆和执行功能的标准化仪器将完成。多元回归和相关分析将用于评估认知表现与AD风险、结构完整性和大脑激活模式的关系。拟议的研究项目与公共卫生有重大关系。阿尔茨海默病影响到社会的各个方面，由于美国人口寿命的延长，它已成为一个日益严重的公共卫生问题。据估计，到2050年，美国的AD患病率将从目前估计的450万人增加到约1130万至1600万人（Hebertetal 2003）。拟议项目的结果可能有助于确定导致AD风险增加的其他因素，从而提高早期发现和针对个体进行早期干预。

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is the most common cause of dementia in adults over the age of 65 in the United States (Evans, 1990). AD is a debilitating disease and has devastating psychological and financial effects on patients, caregivers, families, and society. Early detection is essential to successful treatment (Solomon & Murphy, 2005). Early deficits often involve memory (Salmon & Bondi, 1999), an important topic of study due to its necessary presence in AD diagnosis and its significant impact on functioning. Medial temporal lobe (MTL) structures are involved in the encoding of new information into memory (Squire, 1992) and have been identified as those initially affected by AD neuropathology (Braak & Braak, 1991; Jack et al., 1992). Mild cognitive impairment (Petersen et al., 1999; Tierney et al., 1996) and the epsilon 4 allele for apolipoprotein E (APOE) have been associated with increased risk for AD (Corder et al., 1993). Thus, a long-term objective of this proposal is to develop a program of study using arterial spin labeling (ASL) magnetic resonance imaging (MRI) techniques to examine (a) the response of MTL subregions during encoding in individuals at risk for AD and (b) develop reliable strategies for early identification of these individuals so that they may be targeted for treatments as they are developed. A specific aim of this project is to use ASL MRI in order to expand upon previous findings from other imaging modalities and examine the brain activation patterns of nondemented older adults at rest and during memory encoding. In addition, this project aims to assess MTL morphometry of nondemented older adults. These specific aims will be achieved through group comparison methodologies comparing structural integrity, brain response, cognitive performance, and interactions between these variables. These variables will be compared between older adults at risk for developing AD and a matched sample of older adults not at risk. Standardized instruments assessing learning, memory, and executive functioning will be completed. Multiple regression and- correlation analyses will be employed to assess the relation of cognitive performance with AD risk, structural integrity, and brain activation patterns. The proposed research project has significant relevance to public health. AD affects every segment of society and is a growing public health concern due to the increasing longevity of the U.S. population. It is estimated that the prevalence of AD in the U.S. will increase from its current estimate of 4.5 million people to approximately 11.3 to 16 million people by 2050 (Hebertetal 2003). Results from the proposed project may aid in identifying additional factors contributing to increased risk for developing AD thereby improving early detection and targeting individuals for early intervention.