MRI, Genetics & Cognitive Precursors of AD & Dementia

描述（由申请方提供）：针对脑血管风险因素（CVRF）与认知下降、AD和痴呆有关的证据，启动了AD和痴呆的MRI、遗传学和认知前体。在最初的研究阶段，我们量化了局部、全脑和白色高信号（WMH）体积，确定了Silent的存在或不存在。 在Fragmentary Offspring和Omni队列的2，900多名受试者中进行了脑损伤（SCI）和认知表现（NP）测量。横断面研究结果表明，CVRF易通过血管性脑损伤降低认知能力。我们的初步研究结果与流行病学和临床研究的先前报告一致，表明CVRF负担与认知能力降低相关。我们现在建议通过在这些受试者中重复MR和NP测量来确定脑结构和功能的变化来扩展我们的研究。纵向数据将使我们能够进一步探索这一假设，即在中年期间前瞻性确定的CVRF在导致认知进行性下降的进行性脑损伤中发挥重要作用，从而增加晚年轻度认知障碍（MCI）或痴呆的可能性。此外，Frachial cohort的丰富的家庭结构，以及积累的丰富的家庭遗传数据将有助于分析遗传对这些措施的影响。 为了实现这一目标，我们增加了海马和内嗅皮层的MRI测量，以评估受阿尔茨海默病（AD）影响的大脑区域，以对比CVRF与队列中老年成员的AD过程的影响。此外，我们还实施了脑映射技术的横截面和 纵向分析。这些新的MRI分析将与亚临床血管疾病的测量以及确定更多的新风险因素（如血清同型半胱氨酸）相结合。还将确定患有轻度认知障碍（MCI）的老年人，以探索CVRF、MRI变化与临床相关认知障碍之间的关系。最后，我们将使用广泛的遗传信息来识别具有痴呆症家族史的年轻个体，以探索可能受遗传影响的大脑结构和认知的潜在早期变化。 这些数据将用于检验CVRF和亚临床血管疾病指数与进行性脑损伤导致的认知功能加速下降相关的假设。如果不进行治疗，我们还假设CVRF将导致临床相关的认知障碍，如MCI和痴呆。最后，我们假设，对于有遗传风险的个体，这些过程可能在生命的早期就开始开始。由于控制CVRF可以明显预防临床卒中，因此希望本研究的数据将鼓励控制CVRF并降低认知能力下降和痴呆的可能性。

DESCRIPTION (provided by applicant): The MRI, Genetics and Cognitive Precursors of AD and Dementia was initiated in response to evidence implicating cerebrovascular risk factors (CVRF) in cognitive decline, AD and dementia. In the initial study phase, we quantified regional, total brain and white matter hyperintensity (WMH) volumes, ascertained the presence or absence of Silent Cerebral Infarcts (SCI) and measured cognitive performance (NP) in more than 2,900 subjects of the Framingham Offspring and Omni Cohorts. Cross-sectional findings indicate that CVRF predispose to diminished cognitive performance by way of vascular brain injury. Our initial findings are in concert with previous reports from epidemiological and clinical studies suggesting that CVRF burden is associated with lowered cognitive performance. We now propose to extend our study by determining changes in brain structure and function by repeating the MR and NP measurements in these subjects. Longitudinal data will enable us to further explore the hypothesis that CVRF prospectively ascertained during mid-life play an important role in progressive brain injury leading in turn to progressive decline in cognition, increasing the likelihood of mild cognitive impairment (MCI) or dementia in later life. In addition, the rich family structure of the Framingham cohorts, and the accumulated wealth of family-based genetic data will facilitate analyses of genetic influences on these measures. To achieve this goal, we have added MRI measures of hippocampus and entorhinal cortex to assess brain areas affected by Alzheimer's disease (AD) in order to contrast the impact of CVRF with the AD process amongst the older members of the cohort. In addition, we have implemented brain mapping techniques for cross-sectional and longitudinal analyses. These new MRI analyses will be combined with measures of subclinical vascular disease as well as ascertainment of an expanded number of novel risk factors such as serum homocysteine. Older individuals with mild cognitive impairment (MCI) will also be identified to explore the relationship between CVRF, MRI changes and clinically relevant cognitive impairments. Finally, we will use the extensive genetic information to identify younger individuals with a documented family history of dementia to explore potential early changes in brain structure and cognition that may be under genetic influence. These data will be used to test the hypotheses that CVRF and indices of subclinical vascular disease will be associated with accelerated decline in cognitive function resulting from progressive brain injury. When left untreated, we also hypothesize that CVRF will lead to clinically relevant cognitive impairment such as MCI and dementia. Finally, we hypothesize that for individuals at genetic risk, these processes may begin earlier in life. Since control of CVRF clearly prevents clinical stroke, it is hoped that data from this study will encourage control of CVRF and reduce the likelihood of cognitive decline and dementia.