ARIC Neurocognitive Study (ARIC-NCS)

描述（由申请人提供）：痴呆症和轻度认知障碍（MCI）对美国老龄化人口造成了巨大且日益增加的健康和社会负担。新的研究表明，微血管疾病对痴呆和MCI有重大贡献。一些长期随访的队列研究显示，中年高血压、糖尿病和吸烟与老年痴呆症之间存在强相关性，而老年人研究中的相关性较弱。一项观察性研究将痴呆、MCI和MRI上可观察到的大脑变化与中年血管危险因素联系起来，有望提出目前尚不存在的痴呆预防策略。目的：拟定的ARIC神经认知研究（ARIC-NCS）将通过一项5中心R 01辅助研究和一项大型、双种族前瞻性ARIC队列研究，重点关注中年血管风险因素和标志物对认知障碍的预测。预计预测在非裔美国人和痴呆或MCI被诊断为血管性或伴有MRI脑血管体征的人中特别强。目的是：1）在70-89岁的参与者中按种族和性别估计痴呆/MCI的患病率，2）确定中年血管因素是否（大血管和微血管疾病的危险因素和标志物）预测痴呆、MCI和认知变化，3）确定中年血管因素和痴呆/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）鉴定与认知变化相关的脑标志物，包括跨越17年的3次MRI扫描的MRI缺血负荷和萎缩的进展，以及5）使用跨越基因组的106个SNP鉴定含有认知下降的易感性基因座的基因组区域。设计/方法：对美国4个社区70-89岁的>7000名居民进行的前瞻性研究，在4次既往检查（1987-1999年）（包括中年认知测试）的基础上增加了24年随访评估，包括详细的神经认知评估、视网膜摄影、实验室分析和病历审查。2000例痴呆和MCI病例和对照将接受脑MRI，并对脑血管体征和脑体积进行中心测量。ARIC是这项研究的独特之处，因为已经测量的预测因子包括大血管（颈动脉厚度、斑块和扩张性、外周动脉疾病）和微血管标记物（视网膜小动脉狭窄和切口、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种途径中的止血因子、apoE、基因组中的106个SNP、所有主要心血管风险因子，在许多参与者中，有一次或两次脑MRI检查。含义：ARIC队列中认知和脑变化的中年血管风险因素的纵向观察性研究将阐明痴呆负担的种族差异的潜在因素，并通过确定血管治疗靶点，干预的最佳时机和有用的中间结局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.