Effect of diabetes and AD pathology on brain imaging and cognition in Latino adults

摘要 II型糖尿病（T2DM）增加了患阿尔茨海默病（AD）的风险，但 机制尚未完全理解。降低T2DM患者认知功能下降的风险，并确定 为了确定可能的干预目标，必须了解T2DM如何影响大脑和认知。我们的整体 目标是了解代谢和阿尔茨海默病风险与大脑测量和认知的关系 在200名北方美国拉丁裔中年人中，这是一个未充分研究的群体， 与非拉丁裔白人相比，我们将：1）评估区域大脑的完整性（结构，功能， 血管），与代谢性血液标志物和AD病理风险相关， 2）评估脑血流、血管反应性和脑缺血/再灌注损伤的变化， 空腹基线和摄入75克葡萄糖后2小时之间的功能连接， 代谢标志物的变化，以获得代谢风险如何影响 大脑对葡萄糖摄入的功能和血管反应，以及3）确定神经血管的大脑测量 功能（脑血管反应性、功能连接性、脑血流量和血脑屏障 渗透性），预测认知能力下降和大脑缺陷超过2年，并研究它们与 代谢功能和AD病理学。目前正在努力将糖尿病药物重新用于认知 临床试验实现我们的目标将有助于深入了解T2DM认知功能下降的潜在机制 患有和不患有AD病理的患者，并提供脑成像生物标志物以指导潜在的干预。

Abstract Type II diabetes mellitus (T2DM) increases the risk for developing Alzheimer’s Disease (AD), but the mechanisms are not fully understood. To reduce the risk for cognitive decline in those with T2DM and to identify possible intervention targets, it is imperative to understand how T2DM affects the brain and cognition. Our overall goal is to gain an understanding of how metabolic and Alzheimer’s risk relate to brain measures and cognition in 200 Northern American Latino middle-aged adults, an understudied group that is at higher risk for both T2DM and AD compared with non-Latino Whites. We will: 1) Evaluate regional brain integrity (structural, functional, and vascular) in those with and without T2DM and as related to metabolic blood markers and AD pathology risk as indicated by plasma ptau181 level 2) Evaluate the changes in cerebral blood flow, vascular reactivity, and functional connectivity between fasting baseline and 2 hours after 75 grams of glucose ingestion and relate those changes to changes in metabolic markers to gain a mechanistic understanding of how metabolic risk affects the brain’s functional and vascular response to glucose ingestion, and 3) Identify brain measures of neurovascular function (cerebrovascular reactivity, functional connectivity, cerebral blood flow, and blood brain barrier permeability) that predict cognitive decline and brain deficits over 2 years and investigate their relationship to metabolic function and AD pathology. There are ongoing efforts to repurpose diabetes medications into cognition clinical trials. Achieving our aims will provide insights into the mechanisms underlying cognitive decline in T2DM patients with and without AD pathology, and provide brain imaging biomarkers to guide potential interventions.