Mild Cognitive Impairment: A Prospective Community Study

描述(由申请人提供)：轻度认知障碍：一项前瞻性社区研究。轻度认知障碍(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。在专门的临床环境中，MCI几乎一致地以很高的比率进展为痴呆，并被认为是前驱痴呆的代表。在社区研究中，MCI是一种更不同的状态，进展为痴呆症的风险较小，而且相当大的比例仅保持轻微损害，甚至恢复正常认知。需要更好地了解谁将和不会从MCI发展为痴呆症，以便诊断标准可以基于整个社区的预测有效性，从而使个人能够更适当地针对预防和早期干预。这份申请是为了更新一项新的研究，该研究是从宾夕法尼亚州西部的一个社区随机选择的队列。2008年，该队列完成了2036名65岁老年人的招募，其中大多数人进行了APOE基因分型。我们在重叠的两年周期中进行年度跟踪评估。这项研究旨在从头开始关注MCI，而不是痴呆症典型的更严重的损害。该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症的预测值。除了标准标准外，我们还根据我们队列中的标准数据制定了可靠的认知分类，并开发了一种新的基于网络的专家诊断共识方法。相关的临床和生物学指标被评估为协变量和预测因子。主要的结果衡量标准是进展为痴呆症；我们还检查了临床痴呆症分级、个人认知领域、功能损害和其他评估中的纵向变化衡量标准。我们现在建议将队列再跟踪五年，这样足够多的人将经历这些变化，以支持预测MCI进展为痴呆症的关键分析。新的措施包括对250名个体进行结构磁共振脑成像，以确定在这个社区样本中，皮质和局部萎缩以及白质高信号测量对痴呆症预测的改善程度；分析存储的血清中的6个血管和炎症标记物，以及在所有存储的DNA中对13个与阿尔茨海默病和中风相关的新SNPs进行基因分型。这些新措施反映了对血管风险因素的更大重视。对这一特征良好的老龄化队列的持续跟踪将提高对MCI在整个人群中的异质性的理解，并有助于确定MCI结果的可靠预测因素。 公共卫生相关性：2006至2008年间收集的2000多名65岁成年人的社区队列，对他们的认知能力、日常功能以及几项临床和生物指标进行了仔细评估。通过每年对他们进行跟踪，以确定他们患阿尔茨海默氏症和其他痴呆症的风险，这项研究将提供关键信息，帮助识别那些在专业诊所之外面临痴呆症风险的人。需要这些知识，以便更大社区中的个人能够适当地成为预防和早期干预战略的目标。

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.