ARIC Neurocognitive Study (ARIC-NCS)

描述（由申请人提供）：痴呆症和轻度认知障碍（MCI）给美国老龄化人口带来了巨大且日益严重的健康和社会负担。新研究表明，微血管疾病对痴呆和轻度认知障碍有重大影响。一些长期跟踪的队列显示，中年高血压、糖尿病和吸烟与老年痴呆症有很强的相关性，而对老年人的研究则显示出弱相关性。一项将痴呆症、MCI 和 MRI 可观察到的大脑变化与中年血管危险因素联系起来的观察性研究有望提出目前尚不存在的痴呆症预防策略。目的：拟议的 ARIC 神经认知研究 (ARIC-NCS) 将重点通过 5 中心 R01 辅助研究和大型双种族前瞻性 ARIC 队列研究，根据中年血管危险因素和标志物预测认知障碍。预计对于非裔美国人以及痴呆症或 MCI 被诊断为血管性或伴有 MRI 脑血管体征的人来说，预测效果特别强。目的是：1) 估计 70-89 岁参与者中按种族和性别划分的痴呆/MCI 患病率，2) 确定中年血管因素（大血管和微血管疾病的危险因素和标志物）是否预测痴呆、MCI 和认知变化，3) 确定中年血管因素与痴呆/MCI 之间的关联是否因临床定义的痴呆/MCI 亚型或 MRI 体征而不同，4) 识别与认知相关的大脑标志物变化，包括 17 年 3 次 MRI 扫描中 MRI 缺血负担和萎缩的进展，以及 5) 使用跨越基因组的 106 个 SNP 识别包含认知能力下降易感位点的基因组区域。设计/方法：对美国 4 个社区超过 7000 名 70-89 岁居民进行前瞻性研究，对之前的 4 次检查（1987-1999 年）添加了 24 年的跟踪评估，包括详细的神经认知评估、视网膜摄影、实验室分析和医疗记录审查，其中包括中年认知测试。 2000 名痴呆症和 MCI 病例和对照将接受脑部 MRI 扫描，并集中测量脑血管体征和脑容量。 ARIC 在这项研究中具有独特的地位，因为已经测量的预测因素包括大血管（颈动脉厚度、斑块和扩张性、外周动脉疾病）和微血管标志物（视网膜小动脉狭窄和缺口、视网膜出血、渗出物和微动脉瘤、微量白蛋白尿）、心血管事件、5 个途径中的止血因素、apoE、整个基因组中的 106 个 SNP、所有主要心血管危险因素以及许多疾病参与者之前进行过一两次脑部 MRI 检查。意义：对 ARIC 队列中认知和大脑变化的中年血管危险因素进行纵向观察研究，将阐明痴呆症负担种族差异的潜在因素，并通过确定血管治疗目标、最佳干预时机和有用的中期结果，为预防策略提供科学依据。

DESCRIPTION (provided by applicant): Dementia and mild cognitive impairment (MCI) pose a large and increasing health and societal burden on the aging US population. New studies suggest that microvascular disease makes a substantial contribution to dementia and MCI. A few long-followed cohorts show strong associations of mid-life hypertension, diabetes, and smoking with dementia at older age in contrast to weak associations in studies of the elderly. An observational study relating dementia, MCI and cerebral changes observable on MRI to midlife vascular risk factors has the promise of suggesting dementia prevention strategies where none currently exist. Aims: The proposed ARIC Neurocognitive study (ARIC-NCS) will focus on prediction of cognitive impairment from mid-life vascular risk factors and markers through a 5 center R01 ancillary study to the large, bi-ethnic prospective ARIC cohort study. Prediction is expected to be particularly strong in African-Americans and persons whose dementia or MCI is diagnosed as vascular or accompanied by MRI cerebrovascular signs. Aims are to: 1) estimate the prevalence of dementia/MCI by race and sex in participants aged 70-89, 2) determine whether midlife vascular factors (risk factors and markers of macrovascular and microvascular disease) predict dementia, MCI and cognitive change, 3) determine whether the associations between midlife vascular factors and dementia/MCI differ by dementia/MCI subtype defined clinically or by MRI signs, 4) identify cerebral markers associated with cognitive change, including progression of MRI ischemic burden and atrophy across 3 MRI scans spanning 17 years, and 5) identify genomic regions containing susceptibility loci for cognitive decline, using 106 SNPs spanning the genome. Design/Methods: Prospective study of >7000 residents aged 70-89 in 4 US communities adding a 24-year follow-up evaluation with detailed neurocognitive assessment, retinal photography, lab assays and medical record review to 4 previous exams (1987-1999) which included midlife cognitive testing. Two thousand dementia and MCI cases and controls will undergo cerebral MRI with central measurement of cerebrovascular signs and brain volumes. ARIC is uniquely situated for this research since predictors already measured include macrovascular (carotid thickness, plaque and distensibility, peripheral artery disease) and microvascular markers (retinal arteriolar narrowing and nicking, retinal hemorrhage, exudates, and microaneurysms, microalbuminuria), cardiovascular events, hemostatic factors in 5 pathways, apoE, 106 SNPs across the genome, all major cardiovascular risk factors, and in many participants, one or two prior cerebral MRI exams. Implications: Longitudinal observational study of midlife vascular risk factors for cognitive and cerebral changes in the ARIC cohort will elucidate factors underlying ethnic disparities in dementia burden and provide the scientific basis for prevention strategies by identifying vascular therapeutic targets, optimal timing for interventions and useful intermediate outcomes.