Metabolomics of Neurocognitive Risk for Dementia in Diabetes

2型糖尿病(T2D)是一种主要的流行病，与患者、家庭和 公共医疗体系。它的患病率上升是伴随着糖尿病相关疾病的增加的。 合并症。其中，糖尿病已经成为认知损害的一个可重复的危险因素， 痴呆症。然而，不成比例负担的T2D患者患痴呆症风险的潜在机制 人们对人口的了解很少。这项研究的主要目标是评估假设 糖尿病患者存在神经认知轨迹的代谢特征，这些特征解释了 部分，T2D的欧洲裔美国人和非裔美国人在认知衰退方面的种族差异。这 假说将通过重新检查糖尿病心脏研究(DHS)的神经认知队列来探索 轨迹使用完善的认知电池，识字测试，和被判定的医生诊断 痴呆症。因为神经退行性疾病是认知衰退的代表，是进行性的 在观察临床症状和功能缺陷前几年的病理学发展，无针对性 代谢组学分析将对10年前收集的并与以下各项相关的基线样本进行 认知轨迹。这种方法提供了在显性发作之前识别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体特征的研究。这个 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 研究结果的概括性。这项研究的时机对于对比中年和早晚的变化至关重要 成年期识别第一阶段病理生理变化，促进相关生物标记物的识别 具有改善认知障碍和痴呆的诊断、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.