Mild Cognitive Impairment: A Prospective Community Study

轻度认知障碍：前瞻性社区研究。痴呆是一 导致老年人残疾和死亡的主要原因。其发病率呈指数级增长， 年龄确定独立的风险因素和有效的疾病标志物是实现 预防、改善诊断和治疗。为了加强临床和公共卫生服务， 必须在人口背景下查明这些因素。我们希望再延长五年 年，一项为期15年的轻度认知功能障碍（MCI）前瞻性人群研究， 宾夕法尼亚州西南部低SES地区的痴呆症。最初的丰富的特点 队列现在年龄为80岁以上，痴呆症的风险最大;我们通过以下方式补充了队列： 招募目前年龄在65-74岁的额外参与者，目前样本总数约为1100人。 我们的目标仍然是在人群水平上确定临床上 MCI的相关不良认知结果、认知下降和进展为痴呆。 我们提出了一套新的具体目标，调查与这些疾病相关的新疾病标志物。 结果。我们新的基于质谱的高性能血浆β淀粉样蛋白（Aβ）检测 有可能为阿尔茨海默病提供负担得起的非侵入性筛查。7 T MRI脑部 扫描将允许在亚组中对脑血管完整性进行深入成像， 了解小血管疾病（SVD）在认知能力下降和痴呆中的作用。非 侵入性腕关节活动记录仪将测量睡眠-觉醒节律，我们将检查与 认知结果、Aβ和SVD。GWAS和转录组学将使我们能够检查 全基因组遗传和基因表达数据。我们将评估这三者之间的关系 生物标志物（Aβ，SVD，睡眠），沿着基因组学和基因表达，以及它们之间的相互关系。 相互作用，认知能力下降和痴呆的临床相关结果。 新的光揭示了这些疾病的机制，使用建模技术， 考虑偏差并将子样本的结果推广到整个队列，将导致 新的见解，以帮助减少痴呆症的公共卫生负担。

Mild Cognitive Impairment: A Prospective Community Study. Dementia is a leading cause of disability and death in older adults. Its incidence increases exponentially with age. Identifying independent risk factors and valid disease markers are critical steps towards prevention, improved diagnosis, and treatment. To enhance clinical and public health care, these factors must be identified in population settings. We seek to extend, for a further five years, a 15-year prospective population-based study of mild cognitive impairment (MCI) and dementia in a low SES-area of southwestern Pennsylvania. The original richly characterized cohort is now aged 80+, and at maximum risk for dementia; we have replenished the cohort by recruiting additional participants currently aged 65-74, for a total current sample ~1100. Our objective remains to identify, at the population level, risk factors for clinically relevant adverse cognitive outcomes of MCI, cognitive decline, and progression to dementia. We propose a new set of specific aims investigating novel disease markers in relation to these outcomes. Our new high performing mass-spectrometry-based plasma β amyloid (Aβ) assay holds potential for affordable non-invasive screening for Alzheimer's disease. 7T MRI brain scans will allow in-depth imaging of cerebrovascular integrity in a subgroup and help understand the role of small vessel disease (SVD) in cognitive decline and dementia. Non- invasive wrist actigraphy will measure sleep-wake rhythms which we will examine in relation to the cognitive outcomes, Aβ and SVD. GWAS and transcriptomics will allow us to examine genome-wide genetic and gene expression data. We will assess the relationships of these three biomarkers (Aβ, SVD, sleep), along with genomics and gene expression, and their mutual interactions, to the clinically relevant outcomes of cognitive decline and dementia. New light shed on mechanisms underlying these disorders, using modeling techniques to account for biases and generalize results from sub-samples back to the entire cohort, will lead to new insights to help reduce the public health burden of dementia.