Global vs. Focal Neuroimaging Markers of Dementia Risk

描述（由申请人提供）：我们的目标是使用自动脑MRI读取技术，即自动标记途径（ALP），识别和量化阿尔茨海默病（AD）的特定神经影像学标志物。ALP是一种可靠、易于操作、全自动的技术，可生成区域和全球脑容量测量。作为心血管健康研究（CHS; N01HC85082）的一部分，这个独立的项目对1997- 1999年在匹兹堡获得的532张脑mri进行了二次分析，这是一项多地点观察性研究，旨在调查老年人心血管危险因素。CHS参与者接受了详细的痴呆评估，作为CHS认知研究的一部分（CHS- cs; R01AGO15928）。我们的项目将利用1989年至今收集的大量流行病学数据，包括Lopez博士在匹兹堡进行的后续痴呆症评估（R01AG020098）。脑ALP体积测量将丰富CHS- cs数据集，并将提供给其他CHS研究者。我们建议ALP-全球和局灶性萎缩（海马和内侧颞叶）的测量：1)区分认知正常的老年人与受AD或轻度认知障碍影响的老年人；2)比传统的CHS-CS脑MRI（脑室和白质分级）更好地区分痴呆病例；3)区分那些认知正常的成年人在接下来的5年内转化为痴呆与那些转化为轻度认知障碍或保持认知正常的人。该应用的优势包括：匹兹堡532个脑核磁共振成像的即时可用性，1989年至今的痴呆症病例记录良好，ALP使用的当地支持，广泛的人口统计、遗传和临床数据。根据NIA阿尔茨海默病倡议的最终共识，我们将评估新型和传统脑MRI读数方法测量的收敛有效性，并将测试当特定的神经成像生物标志物被纳入诊断标准时，痴呆症的诊断是否能得到改善。我们还计划优化和支持其他研究者使用ALP方法。该提案的结果将为未来的RO1应用奠定基础，以评估3000多名CHS参与者样本中痴呆症风险的神经影像学标志物，这些参与者的重复mri和超过15年的痴呆症随访数据可用。

DESCRIPTION (provided by applicant): Our goal is to identify and quantify specific neuroimaging markers of Alzheimer Disease (AD) using an automated brain MRI reading technique, the automated labeling pathway (ALP). ALP is a reliable, easy to operate, fully automated technique that generates regional and global volumetric measures of the brain. This self-contained project proposes secondary analysis of 532 brain MRIs acquired in Pittsburgh in 1997-99 as part of the Cardiovascular Health Study (CHS; N01HC85082), a multisite observational study to investigate cardiovascular risk factors in the elderly. CHS participants received a detailed dementia evaluation as part of the Cognition Study of the CHS (CHS-CS; R01AGO15928). Our project will take advantage of the wealth of epidemiologic data collected from 1989 to date, including the follow-up dementia evaluation conducted in Pittsburgh by Dr. Lopez (R01AG020098). ALP volumetric measures of the brain will enrich the CHS-CS dataset and will be available to other CHS investigators. We propose that ALP- measures of global and focal atrophy (hippocampal and medial temporal lobe): 1) differentiate older individuals who are cognitively normal, vs. those who are affected by AD or Mild Cognitive Impairment; 2) discriminate cases of dementia better than conventional CHS-CS brain MRI measures (ventricular and white matter grade); 3) discriminate those cognitively normal adults who convert to dementia over the following 5 years vs. those who convert to MCI or remain cognitively normal. The strengths of this application include: immediate availability of 532 brain MRIs in Pittsburgh, well documented cases of dementia from 1989 to- date, local support for the use of ALP, extensive demographic, genetic and clinical data. In accordance to the Final Consensus of the NIA Alzheimer's initiative, we will evaluate the convergent validity of measures from novel and conventional brain MRI reading methods, and will test if diagnosis of dementia can improve when specific neuroimaging biomarkers are included in the diagnostic criteria. We also plan to optimize and support the use of the ALP method by other investigators. The results of this proposal will lay a foundation for a future RO1 application to assess neuroimaging markers of dementia risk in a sample of over 3,000 CHS participants, for whom repeated MRIs and over 15 years follow up data on dementia are available.