Neural correlates of memory encoding in subtypes of Mild Cognitive Impairment

描述（由申请人提供）：阿尔茨海默病（AD）是老年人痴呆症的最常见原因，是影响美国约500万65岁以上成年人的主要公共卫生问题。在显著临床症状出现之前，开发评估和识别个体的方法对于延长AD患者及其护理者的生活质量至关重要。然而，预测老年人认知能力下降的特定生物学标记仍然难以捉摸。识别临床前阿尔茨海默病潜在标志物的一种方法是检查患该疾病风险较高的个体的大脑功能，例如那些被诊断为轻度认知障碍（MCI）的个体。MCI通常意味着认知功能测试的损伤，但维持完整的整体认知和日常功能水平。MCI的最新定义描述了涉及一个或多个认知领域的原发性记忆障碍（健忘症）或原发性非记忆障碍（非健忘症）个体的临床亚型。然而，在临床和研究实践中缺乏MCI的通用操作定义，导致从MCI到AD的患病率和进展率差异很大。其他因素，如脑血管功能，也可能影响MCI和AD的进展。目前的建议旨在评估脑血流（CBF）测量的脑血管功能，血氧水平依赖（BOLD）反应测量的脑功能，以及患有遗忘性和非遗忘性MCI的老年人以及一组认知完整的老年人的认知之间的关系。此外，将使用两种类型的MCI标准来比较不同MCI分类方案之间功能脑特征的一致性。使用一种同时测量CBF和BOLD反应的新型神经成像技术，本研究将检查情景记忆表现期间MCI的功能激活模式，情景记忆表现是AD患者第一个主要认知功能下降的表现之一。这是一种重要的方法，因为BOLD反应的差异也可能反映脑血管功能的变化，这种变化随着年龄或疾病而变得更加明显，并可能与神经活动混淆。进一步，本研究拟通过研究脑血管疾病风险对MCI患者CBF和BOLD反应的影响，揭示MCI与血管危险因素之间的相互作用。总的来说，该研究将更好地表征MCI亚型的神经血管基础以及脑血管功能对这些个体脑功能的影响。这项研究将为更好地识别AD高风险个体提供信息，以便在早期阶段实施有效的治疗策略，并将评估可能改变MCI向AD进展的因素。据预测，即使是阿尔茨海默病发病的微小延迟也会显著减轻这种疾病的全球负担，因此，更好地了解相互作用增加风险的因素对于改善我们快速老龄化社会中个人的生活是必不可少的。

DESCRIPTION (provided by applicant): Alzheimer's disease (AD), the most common cause of dementia in older adults, is a major public health concern affecting approximately 5 million adults over the age of 65 in the United States. Developing methods to assess and identify individuals prior to the onset of significant clinical symptoms is crucial to extending the quality of life in individuals with AD and their caregivers. However, specific biological markers that predict cognitive decline in older adults remain elusive. One approach to identifying potential markers of preclinical AD is to examine brain function in individuals at higher risk of developing the disease, such as those diagnosed with Mild Cognitive Impairment (MCI). MCI generally implies impairment on tests of cognitive function, but maintenance of intact global cognition and daily functioning levels. Recent definitions of MCI characterize clinical subtypes of individuals with primary memory impairments (amnestic) or primary non-memory impairments (non-amnestic) involving one or more cognitive areas. However, the lack of a universal operational definition of MCI among clinical and research practices results in widely varying prevalence rates and progression rates from MCI to AD. Additional factors, such as cerebrovascular function, may also influence progression of MCI and AD. The current proposal seeks to evaluate the relationship between cerebrovascular function as measured by cerebral blood flow (CBF), brain function as measured by the blood-oxygenation level dependent (BOLD) response, and cognition in older adults with amnestic and non-amnestic MCI, as well as a group of cognitively intact older adults. In addition, two types of MCI criteria will be used to compare the consistency of functional brain profiles between different MCI classification schemes. Using a novel neuroimaging technique that simultaneously measures CBF and BOLD response, this study will examine functional activation patterns in MCI during episodic memory performance, one of the first major cognitive functions to decline in AD. This is an important method because differences in the BOLD response may also reflect variations in cerebrovascular functioning that become more pronounced with age or disease and can be confused with neural activity. Further, this study plans to examine the influence of cerebrovascular disease risk on CBF and BOLD response in MCI to reveal the interaction between MCI and vascular risk factors. Overall, the proposed study will better characterize the neurovascular underpinnings of the MCI subtypes and the influence that cerebrovascular function has on brain function in these individuals. This study will provide information to better identify individuals at higher risk for AD so that effective treatment strategies can be implemented at an early stage and will assess factors that may modify the progression of MCI to AD. As even small delays in the onset of AD are predicted to significantly reduce the global burden of this disease, a better understanding of the factors that interact to increase risk are imperative to improve the lives of individuals in our rapidly aging society. PUBLIC HEALTH RELEVANCE: Current estimates report that approximately 13% of individuals over the age of 65 in the U.S. have Alzheimer's disease (AD) and as the portion of individuals over the age of 65 is expected to double by the year 2030, it is important to assess methods of early detection of AD as well as to prevent or delay cognitive and neurological decline in older adults. The proposed study will focus on better characterizing the neurovascular underpinnings of specific subtypes of Mild Cognitive Impairment (MCI), a risk factor for developing AD, and the influence that vascular function has on brain function in individuals with MCI. This study will provide information to better identify individuals at higher risk for AD so that effective treatment strategies can be implemented at an early stage and will examine factors that may modify the progression of MCI to AD.