Metabolomics of Neurocognitive Risk for Dementia in Diabetes

糖尿病痴呆神经认知风险的代谢组学

基本信息

批准号：
9882933
负责人：
Nicholette D. Allred
金额：
$ 75.76万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9882933
关键词：
Adult African American Aging Alzheimer&apos s disease related dementia American Biological Markers Clinical Cognition Cognitive Cohort Studies Collaborations Data Dementia Diabetes Mellitus Diagnosis Diagnostic Disease Elderly Environment Epidemic Epidemiologist Epidemiology European Evaluation Family Genetic Genetic Markers Goals Healthcare Systems Heart Human Genome Impaired cognition Joints Life Style Maps Measures Memory Modeling Nerve Degeneration Neurocognition Neurocognitive Non-Insulin-Dependent Diabetes Mellitus Outcome Participant Pathology Pathway interactions Patients Performance Physicians Population Prevalence Renal function Reproducibility Risk Risk Factors Role Sampling Symptoms Testing Vascular Diseases Visit Work adjudicate cardiometabolic risk clinical examination cognitive development cognitive performance cohort comorbidity dementia risk ethnic disparity executive function genetic analysis genetic architecture genetic risk factor genome-wide improved insight literacy metabolomics middle age mild cognitive impairment novel outcome forecast protective factors racial disparity response risk prediction model tool

项目摘要

Type 2 diabetes (T2D) is a major epidemic associated with significant burdens on patients, families, and the public healthcare system. Its rise in prevalence is concomitant with an increase in diabetes-related comorbidities. Among these, diabetes has emerged as a reproducible risk factor for cognitive impairment and dementia. However, the mechanisms underlying the risk for dementia in the disproportionately burdened T2D populations are poorly understood. The primary goal of this study is to evaluate the hypothesis that metabolomic signatures of neurocognitive trajectory are present in diabetes and these signatures explain, in part, race disparities in cognitive decline between European Americans and African Americans with T2D. This hypothesis will be explored by re-examining the Diabetes Heart Study (DHS) cohort for neurocognitive trajectory using a well-established cognitive battery, literacy testing, and adjudicated physician diagnosis of dementia. Because neurodegenerative conditions, representative of cognitive decline, are progressive with pathology developing years prior to the observation of clinical symptoms and functional deficits, untargeted metabolomic analysis will be performed on baseline samples collected >10 years prior and correlated with cognitive trajectory. This approach offers the potential to identify relevant biomarkers before onset of overt disease. Finally, a comprehensive genetic analysis of the DHS participants to examine the genetic architecture of neurocognitive measures and metabolomic signatures of neurocognitive change will be performed. The composition of this study, inclusive of European American and African Americans participants, will provide generalizability of the findings. The timing of this study is critical to contrast changes in midlife to early-late adulthood to identify first stage pathophysiological changes facilitating the identification of relevant biomarkers with potential to improve the diagnosis, prognosis and treatment of cognitive impairment and dementia.

2 型糖尿病 (T2D) 是一种主要流行病，给患者、家庭和公众带来沉重负担。公共医疗保健系统。其患病率的上升伴随着糖尿病相关疾病的增加合并症。其中，糖尿病已成为认知障碍和认知障碍的可重复危险因素。失智。然而，在负担过重的 T2D 人群中，痴呆风险的潜在机制人们对人们知之甚少。本研究的主要目标是评估以下假设：神经认知轨迹的代谢组学特征存在于糖尿病中，这些特征解释了，部分是患有 T2D 的欧洲裔美国人和非裔美国人认知能力下降的种族差异。这将通过重新检查糖尿病心脏研究 (DHS) 队列的神经认知功能来探索这一假设使用完善的认知电池、读写能力测试和医生的裁定诊断来确定轨迹失智。因为代表认知能力下降的神经退行性疾病是随着时间的推移而进展的病理学在观察临床症状和功能缺陷之前数年就已形成，无针对性代谢组学分析将对 10 年前收集的基线样本进行，并与认知轨迹。这种方法提供了在明显的疾病发作之前识别相关生物标志物的潜力。疾病。最后，对国土安全部参与者进行全面的遗传分析，以检查遗传结构将进行神经认知测量和神经认知变化的代谢组学特征的分析。这这项研究的组成，包括欧洲裔美国人和非洲裔美国人的参与者，将提供研究结果的普遍性。这项研究的时机对于对比中年与早晚的变化至关重要成年期识别第一阶段病理生理变化，促进相关生物标志物的识别具有改善认知障碍和痴呆症的诊断、预后和治疗的潜力。