Alzheimer's Disease Patient Registry (ADPR)

描述（由申请人提供）：该项目的总体目标是加深我们对以社区为基础的人群中衰老过程和大脑老化的理解。我们的项目在主题上与基于我们自己的研究和文献的先前结果的总体假设相关联：微梗死是晚年脑功能障碍的关键病理生理过程。目标1和目标2将测试关于4种晚年大脑结果的假设：1)痴呆和AD的发展；2)结合复杂的现代心理测量分析的全球认知衰退轨迹；3)标准的显微神经病理指标；4)新的生化神经病理标志物，包括可溶性A(S)低聚物、区域氧化损伤标志物和炎症标志物。目的1。利用独特的临床记录来检验关于中晚期微观和宏观血管状况与晚年大脑结果之间关系的假设。目标1将利用该队列中可获得的117000人年的医疗记录数据。目的。检验与2型糖尿病（DM）相关的假设。我们将确定中年和晚年胰岛素抵抗和高血糖对晚年大脑结果的独立和共同贡献，以确定这些结果是胰岛素抵抗、高血糖还是两者兼而有之的最好解释。目的：检验与肾脏疾病相关的假设。我们将确定中年和晚年肾功能是否与晚年脑预后的高风险相关。目标1 c。检验心房颤动（AF）的相关假设。我们将确定房颤是否与老年脑预后的高风险相关，房颤持续时间和持续时间的增加是否会带来额外的风险增加，以及抗凝改善房颤相关风险的程度。利用独特的ACT研究数据来检验关于晚年身体表现、虚弱和晚年大脑结果之间关系的假设。我们将跟踪我们的初步发现，即在尸检的参与者中，生命中的定时行走与微梗死的存在有关，以更充分地验证定时行走的减少和虚弱的发展先于晚年大脑结果的假设。目标3。继续作为宝贵的科学资源，并改善基础设施，以便利外部使用ACT数据。

DESCRIPTION (provided by applicant): The overall goal of this project is to deepen our understanding of aging processes and the aging brain in a community-based population. Our projects are thematically linked to an overarching hypothesis based on previous results from our own studies and the literature: that microinfarcts are key pathophysiological processes in late life brain dysfunction. Aims 1 & 2 will test hypotheses regarding 4 late-life brain outcomes: 1) Development of dementia and AD; 2) Trajectories of global cognitive decline incorporating sophisticated modern psychometric analyses; 3) Standard microscopic neuropathological measures; and 4) Novel biochemical neuropathological markers, including soluble A(S oligomers, markers of regional oxidative damage, and inflammatory markers. Aim 1. Exploit unique clinical records to test hypotheses about the association between mid- and late-life micro- and macro-vascular conditions and late-life brain outcomes. Aim 1 will take advantage of the >117,000 person-years of medical record data available from the cohort. Aim la. Test hypotheses related to type 2 diabetes (DM). We will identify the independent and joint contributions of mid-life and late-life insulin resistance and hyperglycemia on late-life brain outcomes to determine whether these outcomes are best explained by insulin resistance, hyperglycemia, or both. Aim lb. Test hypotheses related to renal disease. We will determine whether mid-life and late-life renal function is associated with greater risk for late-life brain outcomes. Aim 1c. Test hypotheses related to atrial fibrillation (AF). We will determine whether AF is associated with higher risk for late-life brain outcomes, whether increased persistence and duration of AF convey additional increased risk, and the extent to which anticoagulation ameliorates risks associated with AF. Aim 2. Exploit unique ACT study research data to test hypotheses about the association between late-life measures of physical performance, frailty, and late-life brain outcomes. We will follow-up our preliminary finding that timed walk during life is associated with the presence of microinfarcts among autopsied participants to more fully test the hypotheses that decrements in timed walk and the development of frailty precede late-life brain outcomes. Aim 3. Continue to serve as a valuable scientific resource and improve infrastructure to facilitate external use of ACT data.