Mild Cognitive Impairment: a Prospective Community Study

 描述（由申请人提供）：此竞争性续期申请旨在将Monongahela-Youghiogheny健康老龄化团队（MYHAT）项目再延长5年，该项目是一项为期10年的纵向研究，针对宾夕法尼亚州匹兹堡附近经济萧条的小城镇地区的代表性人群队列。迄今为止，MYHAT一直专注于描述MCI的特征，并确定从MCI进展到痴呆事件的风险因素，并确定了风险关系的相当大的异质性。 根据迄今为止的调查结果， 新的目标是：（1）确定90岁以上老年人痴呆的风险/保护因素，其中发病率继续上升，但几乎没有发现风险因素;（2）确定整个队列中痴呆的血管/炎症/代谢风险因素，特别是糖尿病相关因素;（3）研究出生队列对痴呆和认知能力下降发病率的影响，并确定是否可以用风险和保护因素的长期趋势来解释;（4）利用现有的全基因组基因型数据识别与认知衰退内表型相关的基因，然后在复制样本中进行确认。我们还提出了一个探索性的目标，将淀粉样蛋白和tau PET神经成像扩展到120名MYHAT参与者的亚组中，作为一个独立项目的一部分，本研究不收取任何费用。这里的科学目标是确定与大脑淀粉样蛋白和tau蛋白沉积相关的因素， 确定这些变量是否能预测整个MYHAT队列中的痴呆症。 最初的MYHAT队列（N~ 2，000）在进入研究时年龄为65岁以上，现在年龄为75岁以上，并且具有10年的丰富纵向数据，非常适合实现我们的目标。在过去的9年里，大约有一半的队列因自然减员而流失，包括疾病和死亡。我们将通过招募700名年龄在65-74岁之间的新参与者来补充队列，这些参与者能够提供最大的随访人年，并且还将提高我们调查队列效应的能力。 我们的首要主题是研究MCI和痴呆在人群中的异质性，解构结果以及预测变量，以确定更细粒度的关系，这将揭示潜在的疾病机制。这种方法与转化流行病学的目标是一致的，超越了简单的描述，以确定具有临床和公共卫生意义的风险和保护因素，以及这些因素发挥作用的亚组;生成和测试机制假设;并确定人口趋势与政策和规划的影响。

 DESCRIPTION (provided by applicant): This competing renewal application seeks to extend, for a further 5 years, the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) project, a 10-year longitudinal study of a representative population-based cohort in an economically depressed small-town region near Pittsburgh, PA. MYHAT has thus far focused on characterizing MCI and identifying risk factors for progression from MCI to incident dementia, and identified considerable heterogeneity in risk relationships. Building on findings to date, our new aims are: (1) To identify risk /protective factors for dementia in those aged 90+ years, in whom incidence continues to rise but few risk factors have been found; (2) To identify vascular / inflammatory/ metabolic risk factors, particularly diabetes-related factors, for dementia in the cohort as a whole ; (3) To examine birth cohort effects in the incidence of dementia and cognitive decline, and determine whether they can be explained by secular trends in risk and protective factors; (4) To identify genes associated with cognitive decline endophenotypes using existing genome-wide genotype data and then confirming in a replication sample. We also propose an exploratory aim to extend amyloid and tau PET neuroimaging into a subgroup of 120 MYHAT participants, at no cost to this study, as part of an independent project. Here the scientific objective is to identify factors associated with cerebral amyloid and tau deposition and determine whether those variables predict dementia in the MYHAT cohort as a whole. The original MYHAT cohort (N~2,000) aged 65+ years at study entry is now aged 75+ and has 10 years of rich longitudinal data that are ideal for achieving our aims. About half the cohort has been lost to attrition, including illness and mortality, over the past 9 years. We will replenish te cohort by recruiting 700 new participants aged 65-74 who are able to contribute the maximum person-years of followup, and will also enhance our ability to investigate cohort effects. Our over-arching theme is to investigate the heterogeneity of MCI and dementia in the population at large, deconstructing the outcomes as well as the predictor variables to identify finer-grained relationships which will shed light on underlying disease mechanisms. This approach is consistent with the goals of translational epidemiology, going beyond simple description to identify risk and protective factors with clinical and public health significance, and the subgroup in which these factors operate; generate and test mechanistic hypotheses; and identify population trends with implications for policy and planning.