Wisconsin Registry for Alzheimer Prevention: Biomarkers of Preclinical AD

威斯康星州阿尔茨海默病预防登记处：临床前 AD 的生物标志物

• 批准号: 7404515
• 负责人: Mark Sager
• 金额: $ 70.8万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-15 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7404515
• 关键词: Adult Children; Adverse effects; Affect; Age; Alleles; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid beta-Protein; Apolipoprotein E; Apolipoproteins; Archives; Biological Markers; Blood Vessels; Brain; Brain region; Cerebrospinal Fluid; Child; Cognition; Cognitive; Cognitive aging; Cohort Studies; Control Groups; Country; Data; Dementia; Development; Disease; Disease Progression; Early Diagnosis; Early Intervention; Economics; Environmental Health; Episodic memory; Evaluation; Exhibits; Family history of; Family member; Functional Imaging; Functional Magnetic Resonance Imaging; Genetic; Genetic Risk; Genotype; Goals; Health; Heredity; Hippocampus (Brain); Impaired cognition; Individual; Inherited; Intervention; Knowledge; Laboratories; Learning; Life Style; Memory; Neurobiology; Neuropsychological Tests; Onset of illness; Parents; Participant; Pattern; Personal Satisfaction; Persons; Plasma; Positioning Attribute; Prevalence; Prevention strategy; Primary Prevention; Prospective Studies; Purpose; Rate; Registries; Research; Research Personnel; Risk; Risk Factors; Sampling; Siblings; Structure; Syndrome; Testing; Universities; Wisconsin; age related; aging brain; apolipoprotein E-4; brain volume; cognitive change; cognitive function; cohort; disorder control; executive function; experience; middle age; neuropsychological; pre-clinical; prevent; programs; prospective; social

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.

描述（由申请人提供）：阿尔茨海默氏病（AD）患病率的预期快速增加将对这个国家的经济和社会结构产生重大影响，因此，迫切需要专注于制定早期干预和预防策略的研究。制定 AD 一级预防策略的一种方法是研究未患有痴呆症但患该疾病的风险可能增加的中年个体发生的认知和神经生物学变化。其中一个群体是 AD 患者的成年子女，由于与受影响的父母共有的遗传、环境和健康风险因素，他们患这种疾病的风险增加。由于威斯康星州阿尔茨海默病预防登记处 (WRAP) 的存在，威斯康星大学准备开展此类研究。 WRAP 特别关注 AD 患者的成年子女，以促进早期发现并制定策略以降低患 AD 的风险。迄今为止，我们已经存档了 DMA、血浆和血清样本，并对超过 825 名 AD 患者的成年子女和无家族史的对照受试者进行了广泛的评估。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学测试以及结构和功能 MRI，以确定 4 年重新测试间隔内认知变化的模式和预测因素。我们的长期目标是 识别与异常认知老化和 AD 发展相关的健康和生活方式变量，并利用这些信息制定预防或延缓该疾病发作的干预措施。我们的总体假设是，AD 患者的成年子女将表现出异常认知衰老的迹象，伴有学习、记忆和执行功能下降，以及体积和功能磁共振成像异常，这些迹象可以通过 AD 的特定遗传、血管和生活方式危险因素来预测。具体目标是： 1) 确定 AD 家族史和载脂蛋白 (APOE) 4 等位基因对参与者认知衰老的差异影响； 2）确定血管和生活方式危险因素对参与者认知衰老的影响； 3) 检查 AD 家族史和 APOE 4 等位基因对大脑衰老的不同影响，这一影响是通过情景记忆测试期间脑容量纵向下降率和功能磁共振成像激活来确定的，已知这些测试会激活受 AD 影响的大脑区域。