Mild Cognitive Impairment: A Prospective Community Study

轻度认知障碍：一项前瞻性社区研究

• 批准号: 8522094
• 负责人: MARY GANGULI
• 金额: $ 136.7万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8522094
• 关键词: Abbreviations; Adult; Affect; Aging; Alzheimer' s Disease; Ankle; Atrophic; Biological; Biological Assay; Blood Pressure; Blood Vessels; Brain; Brain imaging; Cardiovascular Diseases; Cerebrovascular Disorders; Characteristics; Classification; Clinic; Clinical; Cognition; Cognitive; Cohort Studies; Communities; Consensus; DNA; DSM-V; Data; Dementia; Development; Diagnostic; Early Intervention; Early intervention trials; Elderly; Epidemiology; Etiology; Genes; Genetic; Genotype; Glossary; Goals; Gold; Health; Heterogeneity; Human; Impaired cognition; Impairment; Individual; Inflammatory; Intervention; Knowledge; Literature; Magnetic Resonance Imaging; Measurement; Measures; Meta-Analysis; Nature; Online Systems; Outcome; Outcome Measure; Participant; Pharmaceutical Preparations; Policies; Population; Predictive Value; Prevalence; Prevention; Preventive Intervention; Process; Protocols documentation; Public Health; Publishing; Recording of previous events; Relative (related person); Request for Applications; Research; Research Design; Risk; Risk Factors; Sampling; Scientist; Serum; Serum Markers; Services; Staging; Stroke; Subgroup; System; Time; Vascular Diseases; Work; aged; aging population; arm; base; behavior measurement; cerebral atrophy; cognitive change; cohort; community setting; cost; design; functional disability; healthy aging; improved; inflammatory marker; innovation; medical specialties; meetings; mental state; mild cognitive impairment; normal aging; novel; novel diagnostics; pathological aging; population based; pre-clinical; primary outcome; prospective; public health relevance; vascular factor; white matter

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.

描述（由申请人提供）：轻度认知障碍：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。在专业临床环境中，MCI几乎一致地以高速率进展为痴呆，并被认为代表前驱痴呆。在社区研究中，MCI是一种更异质的状态，进展为痴呆的风险较低，并且相当大的比例仅保持轻度受损甚至恢复正常认知。需要更好地了解谁会和不会从MCI进展到痴呆症，以便诊断标准可以基于整个社区的预测有效性，并且可以更适当地针对个人进行预防和早期干预。本申请用于更新从西PA社区随机选择的队列的新研究。2008年，该队列完成了2036名65岁以上的个体的招募，其中大多数人进行了APOE基因分型。我们在重叠的2年周期中进行年度随访评估。这项研究是重新设计的，重点是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存的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。除了标准的标准，我们还开发了可靠的认知分类相对于我们的队列的规范性数据，和一种新的基于网络的方法，专家诊断共识。相关的临床和生物学指标作为协变量和预测因子进行评估。主要结局指标是进展为痴呆;我们还检查了临床痴呆评级、个体认知领域、功能障碍和其他评估的纵向变化指标。我们现在建议再跟踪该队列五年，以便有足够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。新的测量方法包括：对250名个体进行结构MRI脑成像，以确定皮质和区域萎缩以及白色物质高信号的测量在多大程度上改善了该社区样本中痴呆的预测;对储存的血清中的6种血管和炎症标记物进行分析，并对所有储存的DNA中与阿尔茨海默病和中风相关的13种新的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。对这一特征良好的老龄队列的持续随访将提高对MCI在总体人群中异质性的理解，并有助于确定MCI结局的可靠预测因子。 公共卫生相关性：2006年至2008年期间，对2,000多名65岁以上的成年人进行了社区队列研究，对他们的认知能力、日常功能以及几项临床和生物学指标进行了仔细评估。通过每年跟踪他们以确定他们患阿尔茨海默氏症和其他痴呆症的风险，该研究将提供关键信息，以帮助确定那些在专业诊所环境之外有痴呆症风险的人。这种知识是必要的，以便更大社区中的个人可以适当地成为预防和早期干预战略的目标。