Wisconsin Registry for Alzheimer Prevention: Biomarkers of Preclinical AD

描述(申请人提供)：预计阿尔茨海默病(AD)患病率的快速增长将对这个国家的经济和社会结构产生重大影响，因此，迫切需要研究重点是制定早期干预和预防战略。制定AD初级预防策略的一种方法是研究没有痴呆症但可能有更高患病风险的中年人发生的认知和神经生物学变化。其中一个群体是阿尔茨海默病患者的成年子女，由于遗传、环境和健康风险因素与受影响的父母相同，他们患上这种疾病的风险增加。威斯康星大学准备进行这样一项研究，因为威斯康星州阿尔茨海默氏症预防登记处(WRAP)的存在。WRAP特别关注阿尔茨海默病患者的成年子女，努力促进及早发现并制定战略，以降低患阿尔茨海默病的风险。到目前为止，我们已经存档了DMA、血浆和血清样本，并对825名AD患者和没有家族病史的对照组的成年子女进行了广泛的评估。这项前瞻性队列研究的目的是进行第二波实验室和神经心理测试以及结构和功能磁共振成像，以确定在4年的重测间隔内认知变化的模式和预测因素。我们的长期目标是 确定与认知异常老化和阿尔茨海默病发展相关的健康和生活方式变量，并利用这些信息开发预防或推迟疾病发病的干预措施。我们的总体假设是，AD患者的成年子女将表现出异常认知老化的迹象，学习、记忆和执行功能下降，体积和功能磁共振异常，这将由AD的特定遗传、血管和生活方式风险因素预测。具体目的是：1)确定AD家族史和载脂蛋白(APOE)4等位基因对受试者认知老化的不同影响；2)确定血管和生活方式危险因素对受试者认知老化的影响；以及3)考察AD家族史和APOE 4等位基因对脑老化的不同影响，这取决于在情景记忆测试中脑体积纵向下降的速度和已知激活受AD影响的大脑区域的功能磁共振成像(FMRI)激活。

DESCRIPTION (provided by applicant): The expected rapid increase in the prevalence of Alzheimer's disease (AD) will have a significant impact on the economic and social structure of this country and as a result, there is a critical need for research focusing on developing early intervention and prevention strategies. One approach to developing primary prevention strategies for AD is to study cognitive and neurobiological changes occurring in middle-aged individuals who do not have dementia but may be at increased risk for developing the disease. One such group is the adult children of persons with AD who are at increased risk of developing the disease due to heredity, environmental and health risk factors shared with affected parents. The University of Wisconsin is prepared to conduct such a study because of the existence of the Wisconsin Registry for Alzheimer's Prevention (WRAP). WRAP focuses specifically on adult children of persons with AD in an effort to facilitate early detection and develop strategies to reduce the risk of developing AD. To date, we have archived DMA, plasma and serum samples and conducted extensive assessments on over 825 adult children of persons with AD and control subjects without a family history. The purpose of this prospective cohort study is to conduct a second wave of laboratory and neuropsychological testing and structural and functional MRI in order to define patterns and predictors of cognitive change over a 4-year re-test interval. Our long term goal is to identify health and lifestyle variables associated with abnormal cognitive aging and the development of AD and to use this information to develop interventions that will prevent or delay the onset of the disease. Our overall hypothesis is that adult children of persons with AD will exhibit signs of abnormal cognitive aging with declines in learning, memory and executive function and volumetric and fMRI abnormalities that will be predicted by specific genetic, vascular and lifestyle risk factors for AD. The Specific Aims are: 1) determine the differential effects of family history of AD and apolipoprotein (APOE) 4 allele on the cognitive aging of participants; 2) determine the effects of vascular and lifestyle risk factors on the cognitive aging of participants; and 3) examine the differential effect of family history of AD and the APOE 4 allele on brain aging as determined by rates of longitudinal decline in brain volume and fMRI activation during episodic memory tests that are known to activate regions of the brain affected by AD.