Metabolomics of Neurocognitive Risk for Dementia in Diabetes

2型糖尿病（T2 D）是一种主要的流行病，与患者、家庭和患者的重大负担相关。 公共医疗体系。其患病率的上升是伴随着糖尿病相关的 合并症。其中，糖尿病已成为认知障碍的可重复风险因素， 痴呆然而，在负担不成比例的T2 D患者中， 人们对人口了解甚少。本研究的主要目的是评估假设， 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，欧洲裔美国人和非洲裔美国人之间的T2 D认知下降的种族差异。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讨这一假设。 轨迹使用一个完善的认知电池，识字测试，并裁定医生诊断 痴呆因为神经退行性疾病，代表认知能力下降，是渐进的， 在观察到临床症状和功能缺陷前数年发生的病理学，非靶向 将对>10年前收集的基线样本进行代谢组学分析，并与 认知轨迹这种方法提供了在显性遗传病发作前鉴定相关生物标志物的可能性。 疾病最后，对DHS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 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 调查结果的普遍性。这项研究的时间对于对比中年和早期-晚期的变化至关重要。 成年期，以确定第一阶段的病理生理学变化，促进相关生物标志物的鉴定 具有改善认知障碍和痴呆症的诊断、预后和治疗的潜力。

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.