MRI, Genetics & Cognitive Precursors of AD & Dementia

核磁共振、遗传学

• 批准号: 6875317
• 负责人: PHILIP A WOLF
• 金额: $ 120.15万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6875317
• 关键词: Alzheimer' s disease; bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain mapping; clinical research; cognition; dementia; disease /disorder proneness /risk; entorhinal cortex; family genetics; genetic susceptibility; hippocampus; human subject; longitudinal human study; magnetic resonance imaging; nervous system disorder epidemiology; neuropathology; neuropsychological tests

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.

描述（由申请人提供）：AD和痴呆症的MRI，遗传学和认知前体是针对涉及脑血管危险因素（CVRF）在认知下降，AD和痴呆症中的证据的响应。在最初的研究阶段，我们量化了区域，总脑和白质高强度（WMH）体积，确定存在或不存在静音 脑梗塞（SCI）和2,900多名弗雷明汉后代和OMNI同伴的受试者中测量了认知表现（NP）。横截面发现表明，CVRF易于通过血管脑损伤降低认知性能。我们的最初发现与流行病学和临床研究的先前报道一致，这表明CVRF负担与认知表现降低有关。现在，我们建议通过重复这些受试者中的MR和NP测量值来确定大脑结构和功能的变化来扩展研究。纵向数据将使我们能够进一步探讨以下假设：CVRF在中年期间确定的CVRF在渐进性脑损伤中发挥了重要作用，导致认知逐渐下降，增加了轻度认知障碍（MCI）或痴呆症的可能性。此外，弗雷明汉同伙的丰富家庭结构以及基于家庭的遗传数据的积累将有助于分析对这些措施的遗传影响。 为了实现这一目标，我们添加了海马和内嗅皮层的MRI测量方法，以评估受阿尔茨海默氏病影响的大脑区域（AD），以对比CVRF与同胞较旧成员的AD过程的影响。此外，我们还实施了横截面和 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扩展的新型风险因素（如血清同型半胱氨酸）相结合。还将确定患有轻度认知障碍的老年人（MCI），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具有痴呆症家族史的年轻人，以探索可能在遗传影响下的大脑结构和认知的潜在早期变化。 这些数据将用于检验假设，即CVRF和亚临床血管疾病的指标将与导致脑损伤导致认知功能的加速下降有关。当不进行治疗时，我们还假设CVRF将导致临床相关的认知障碍，例如MCI和痴呆症。最后，我们假设对于处于遗传风险的个体，这些过程可能会在生活中开始。由于对CVRF的控制明显阻止了临床中风，因此希望这项研究的数据能够鼓励控制CVRF并降低认知能力下降和痴呆的可能性。