Mild Cognitive Impairment: A Prospective Community Study

轻度认知障碍：一项前瞻性社区研究。痴呆症是一种 老年人残疾和死亡的主要原因。其发病率随着以下因素呈指数增长 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、改进诊断和治疗。为了加强临床和公共卫生保健， 必须在人口环境中确定这些因素。我们寻求再延长五年 年，一项为期15年的基于人群的轻度认知障碍(MCI)和 宾夕法尼亚州西南部低社会经济地位地区的痴呆症。原著具有丰富的特征 队列现在80岁以上，痴呆症风险最大；我们通过以下方式补充了队列 招募更多目前年龄在65-74岁的参与者，目前的样本总数约为1100人。 我们的目标仍然是在人群水平上确定临床上 与MCI相关的认知不良后果、认知能力下降和进展为痴呆。 我们提出了一套新的特定目标，研究与这些相关的新的疾病标记物。 结果。我们新的基于高效质谱学的血浆β淀粉样蛋白(Aβ)分析 具有负担得起的非侵入性阿尔茨海默病筛查的潜力。7T磁共振脑成像 扫描将允许对子组中的脑血管完整性进行深入成像，并有助于 了解小血管疾病(SVD)在认知功能减退和痴呆中的作用。非- 有创手腕动作记录仪将测量睡眠-觉醒节律，我们将检查与 认知结果、A-β和奇异值分解。GWAS和转录组学将使我们能够检查 全基因组的遗传和基因表达数据。我们将评估这三个人之间的关系 生物标记物(Aβ、SVD、睡眠)以及基因组学和基因表达及其相互作用 相互作用与认知衰退和痴呆症的临床相关结果。 使用建模技术对这些疾病的潜在机制进行了新的揭示 考虑偏差并将子样本的结果推广回整个队列，将导致 帮助减轻痴呆症公共卫生负担的新见解。

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.