ARIC Neurocognitive Study (ARIC-NCS)

描述（由申请人提供）：痴呆症和轻度认知障碍（MCI）对美国老龄化人口构成了巨大且不断增加的健康和社会负担。新的研究表明，微血管疾病是痴呆和轻度认知障碍的重要诱因。一些长期跟踪的队列研究显示，中年高血压、糖尿病和吸烟与老年痴呆有很强的关联，而对老年人的研究则存在较弱的关联。一项观察性研究将痴呆症、轻度认知障碍和MRI观察到的大脑变化与中年血管危险因素联系起来，有望为目前尚不存在的痴呆症预防策略提供建议。目的：拟议的ARIC神经认知研究（ARIC- ncs）将通过一项大型、双种族前瞻性ARIC队列研究的5中心R01辅助研究，重点研究中年血管危险因素和标志物对认知障碍的预测。预测在非裔美国人和诊断为血管性痴呆或MCI或伴有MRI脑血管症状的患者中尤其明显。目标是：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之间的相关性是否因临床定义的痴呆/MCI亚型或MRI体征而有所不同；包括跨越17年的3次MRI扫描的MRI缺血性负担和萎缩的进展，以及5)使用跨越基因组的106个snp确定包含认知能力下降易感性位点的基因组区域。设计/方法：对美国4个社区70-89岁的居民进行前瞻性研究，并进行24年的随访评估，包括详细的神经认知评估、视网膜摄影、实验室分析和既往4次检查（1987-1999）的医疗记录回顾，其中包括中年认知测试。2000名痴呆和轻度认知障碍患者和对照组将接受大脑MRI检查，并对脑血管体征和脑容量进行中心测量。ARIC在这项研究中处于独特的位置，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）和微血管标志物（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、所有主要心血管危险因素，并且在许多参与者中，一到两次脑部核磁共振检查。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，将阐明痴呆负担的种族差异因素，并通过确定血管治疗靶点、最佳干预时机和有用的中间结果，为预防策略提供科学依据。公共卫生相关性：ARIC-NCS将为识别可能从危险因素调整中获益的痴呆风险较高的群体提供手段。鉴于痴呆症和轻度认知障碍的规模日益扩大，实现了与血管疾病的强烈关联，以及合理假设痴呆症和轻度认知障碍（如中风）的风险可以通过调整风险因素大大降低，其公共卫生相关性是显而易见的。

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. PUBLIC HEALTH RELEVANCE: ARIC-NCS will provide the means for identifying groups at greater risk for dementia who might benefit from risk factor modification. Its public health relevance is evident given the growing magnitude of dementia and mild cognitive impairment, the realization of a strong association with vascular disease, and the reasonable assumption that the risk of dementia and mild cognitive impairment, like strokes, can be substantially reduced by risk factor modification.