Mild Cognitive Impairment: A Prospective Community Study

轻度认知障碍：一项前瞻性社区研究

• 批准号: 10047375
• 负责人: Carmen Andreescu
• 金额: $ 293.9万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10047375
• 关键词: Abbreviations; Adult; Age; Alleles; Alzheimer disease screening; Alzheimer' s Disease; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Area; Back; Biological Assay; Biological Markers; Blood; Brain; Brain scan; Candidate Disease Gene; Cerebrovascular Disorders; Cessation of life; Clinical; Cognitive; Cohort Studies; Communities; Data; Dementia; Diagnosis; Diagnostic; Disease; Disease Marker; Education; Elderly; Etiology; Gender; Gene Expression; Genes; Genetic; Genomics; Glossary; Goals; Health; Healthcare; Heterogeneity; Image; Impaired cognition; Incidence; Investigation; Light; Literature; Magnetic Resonance Imaging; Mass Spectrum Analysis; Measures; Mediating; Mediation; Medical; Mendelian randomization; Mental Depression; Microvascular Dysfunction; Modeling; Names; Outcome; Participant; Pennsylvania; Plasma; Population; Population Study; Predictive Factor; Prevention; Public Health; Quantitative Trait Loci; Race; Risk; Risk Factors; Role; Sampling; Selection Bias; Sleep; Sleep Wake Cycle; Structure; Subgroup; Techniques; Testing; Variant; Weight; White Matter Hyperintensity; Woman; Work; Wrist; actigraphy; aged; apolipoprotein E-4; base; causal model; cerebrovascular; cerebrovascular imaging; clinically relevant; cognitive performance; cohort; comorbidity; dementia risk; differential expression; disability; genetic association; genetic variant; genome wide association study; genome-wide; healthy aging; improved; insight; low socioeconomic status; men; mild cognitive impairment; novel; novel marker; outcome prediction; population based; prospective; recruit; sex; spelling; time use; transcriptome sequencing; transcriptomics

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.

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。其发病率呈指数增长 年龄。确定独立的危险因素和有效的疾病标志物是实现这一目标的关键步骤 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。我们寻求再延长五个 年，一项针对轻度认知障碍 (MCI) 的 15 年前瞻性人群研究 宾夕法尼亚州西南部社会经济地位较低地区的痴呆症。原创内容丰富，特色鲜明 该群体目前年龄已超过 80 岁，患痴呆症的风险最大；我们已经补充了队列 招募目前年龄在 65-74 岁之间的其他参与者，当前样本总数约为 1100 人。 我们的目标仍然是在人群水平上确定临床风险因素 MCI 的相关不良认知结果、认知能力下降和进展为痴呆。 我们提出了一组新的具体目标，调查与这些相关的新疾病标志物 结果。我们新型基于高性能质谱的血浆 β 淀粉样蛋白 (Aβ) 检测 具有对阿尔茨海默病进行经济实惠的非侵入性筛查的潜力。 7T 脑部核磁共振 扫描将允许对亚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) 在认知能力下降和痴呆中的作用。非- 侵入性腕部体动记录仪将测量睡眠-觉醒节律，我们将对其进行检查 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。我们将评估这三者的关系 生物标志物（Aβ、SVD、睡眠），以及基因组学和基因表达，以及它们的相互关系 相互作用，与认知能力下降和痴呆的临床相关结果。 使用建模技术揭示这些疾病背后的机制 考虑偏差并将子样本的结果概括回整个队列，将导致 新见解有助于减轻痴呆症的公共卫生负担。