MRI, Genetics & Cognitive Precursors of AD & Dementia

描述(申请人提供)：AD和痴呆症的MRI、遗传学和认知前体是根据证据表明脑血管风险因素(CVRF)与认知功能减退、AD和痴呆症有关而发起的。在最初的研究阶段，我们量化了局部、整个大脑和白质高强度(WMH)体积，确定了Silent的存在或不存在 在Framingham子代和OMNI队列的2900多名受试者中，进行了脑梗塞(SCI)和认知表现(NP)的测量。横断面研究结果表明，CVRF容易通过血管性脑损伤而导致认知能力下降。我们的初步发现与之前的流行病学和临床研究报告一致，这些报告表明CVRF负担与认知能力下降有关。我们现在建议扩展我们的研究，通过重复这些受试者的MR和NP测量来确定大脑结构和功能的变化。纵向数据将使我们能够进一步探索这一假说，即中年期间前瞻性确定的CVRF在进行性脑损伤中发挥重要作用，从而导致认知能力的进行性下降，增加晚年发生轻度认知障碍(MCI)或痴呆的可能性。此外，弗雷明翰群体丰富的家庭结构和基于家庭的遗传数据积累的财富将有助于分析遗传对这些衡量标准的影响。 为了实现这一目标，我们增加了海马体和内嗅觉皮质的MRI测量，以评估受阿尔茨海默病(AD)影响的大脑区域，以便在队列中的老年成员中对比CVRF和AD过程的影响。此外，我们还实施了横断面和横断面脑电地形图技术 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新的风险因素，如血清同型半胱氨酸相结合。患有轻度认知障碍(MCI)的老年人也将被确定，以探索CVRF、MRI变化和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有记录在案的痴呆症家族史的年轻个体，以探索可能受到遗传影响的大脑结构和认知的潜在早期变化。 这些数据将被用来检验CVRF和亚临床血管疾病指数将与进行性脑损伤导致的认知功能加速下降有关的假设。如果不治疗，我们还假设CVRF将导致临床相关的认知损害，如MCI和痴呆症。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了。由于对CVRF的控制明显预防了临床中风，希望这项研究的数据将鼓励对CVRF的控制，并减少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.