Mild Cognitive Impairment: A Prospective Community Study

描述（申请人提供）：轻度认知障碍：一项前瞻性社区研究。轻度认知障碍（Mild Cognitive Impairment， MCI）是介于正常衰老和痴呆之间的认知状态。MCI存在多个术语、定义和标准集。在特殊的临床环境中，MCI几乎一致地以高比率发展为痴呆，并被认为是前驱痴呆的代表。在社区研究中，轻度认知损伤是一种异质性更强的状态，其发展为痴呆的风险较低，并且相当大比例的患者仅轻度受损，甚至恢复到正常认知。我们需要更好地了解哪些人会、哪些人不会从轻度认知障碍发展为痴呆症，这样诊断标准就可以基于整个社区的预测有效性，这样个人就可以更合适地进行预防和早期干预。本申请是为了更新一项新研究，该研究随机选择了一个来自PA西部社区的队列。2008年，该队列完成了2036名65岁以上个体的招募，其中大多数人都有APOE基因分型。我们以重叠的2年周期进行年度跟踪评估。这项研究是重新设计的，重点是轻度认知障碍，而不是痴呆症典型的更严重的损伤。评估方案允许应用许多现有的MCI分类系统和标准集，从而允许在随访期间比较它们对痴呆的预测值。除了标准标准，我们还开发了可靠的认知分类相对于规范数据从我们的队列，和一个新的基于网络的方法来专家诊断共识。相关临床和生物学指标作为协变量和预测因子进行评估。主要结局指标是痴呆进展情况；我们还研究了临床痴呆评分、个体认知领域、功能损伤和其他评估的纵向变化测量。我们现在建议对该队列再进行5年的随访，以便有足够的个体经历这些变化，从而为预测MCI进展为痴呆的关键分析提供动力。新的测量方法包括在250个个体中进行结构MRI脑成像，以确定皮层和区域萎缩和白质高强度测量在多大程度上改善了该社区样本中痴呆症的预测；检测储存的血清中的6种血管和炎症标记物，并在所有储存的DNA中对13个与阿尔茨海默病和中风相关的新snp进行基因分型。这些新措施反映了对血管危险因素的进一步重视。对这一特征明确的老年队列的持续随访将提高对MCI在整个人群中的异质性的理解，并有助于确定MCI结局的可靠预测因素。

DESCRIPTION (provided by applicant): Mild Cognitive Impairment: a Prospective Community Study. Mild Cognitive Impairment (MCI) is the cognitive state intermediate between normal aging and dementia. Multiple terms, definitions, and criterion sets exist for MCI. In specialty clinical settings, MCI almost uniformly progresses to dementia at a high rate, and is assumed to represent prodromal dementia. In community studies, MCI is a more heterogeneous state with less elevated risk of progression to dementia, and with substantial proportions remaining only mildly impaired or even reverting to normal cognition. A better understanding is needed of who will and will not progress from MCI to dementia, so that diagnostic criteria can be based on predictive validity in the community at large, and so that individuals can be more appropriately targeted for prevention and early intervention. This application is for renewal of a new study of a cohort randomly selected from a community in Western PA. In 2008, the cohort completed recruitment of 2036 individuals aged 65+, and the majority of them have had APOE genotyping. We conduct annual followup assessments in overlapping 2-year cycles. This study was designed de novo to focus on MCI rather than on the more severe impairments typical of dementia. The assessment protocol allows the application of many extant classification systems and criterion sets for MCI, thus allowing their predictive values for dementia to be compared during followup. Besides the standard criteria, we have also developed reliable cognitive classifications relative to normative data from our cohort, and a novel web-based approach to expert diagnostic consensus. Relevant clinical and biological measures are assessed as covariates and predictors. The primary outcome measure is progression to dementia; we also examine longitudinal change measures in clinical dementia rating, individual cognitive domains, functional impairment, and other assessments. We now propose to follow the cohort for a further five years, so that sufficient individuals will undergo these changes to power the key analyses predicting progression to dementia from MCI. New measures include structural MRI brain imaging in 250 individuals to determine the extent to which measures of cortical and regional atrophy and white matter hyperintensities improve prediction of dementia in this community sample; assays of 6 vascular and inflammatory markers in stored serum, and genotyping for 13 new SNPs associated with Alzheimer's disease and stroke in all stored DNA. These new measures reflect an expanded emphasis on vascular risk factors. Continued followup of this well- characterized aging cohort will improve understanding of the heterogeneity of MCI in the population at large, and help identify reliable predictors of the outcomes of MCI. PUBLIC HEALTH RELEVANCE: A community-based cohort of over 2,000 adults aged 65+ years, assembled between 2006 and 2008, has been carefully assessed on their cognitive abilities, everyday functioning, and on several clinical and biological measures. By following them annually to determine their risk of developing Alzheimer's and other dementias, the study will provide critical information to help identify those at risk of dementia outside specialty clinic settings. This knowledge is needed so that individuals in the larger community can be appropriately targeted for prevention and early intervention strategies.