BRAIN IN DIABETES: RESPONSE TO INCREASED METABOLIC DEMAND

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。海马体，一个位于颞叶深处的大脑结构，是学习和记忆的关键。研究人员和其他几个小组已经表明，在正常的老年人中，核磁共振成像确定的海马体体积与近期的记忆表现直接相关。该研究假设外周糖代谢异常与mri衍生的海马体积减少和近期记忆表现之间存在特定关联，并且相对于对照组，2型糖尿病患者的海马和记忆减少比糖尿病前期患者更大。此外，这些关系将是解剖学和神经心理学特异性的，并且在考虑到整体脑萎缩后仍将存在。它还假设脑灌注反应性将预测记忆表现和海马体积。研究表明，糖尿病患者对乙酰唑胺的脑血管反应迟钝，记忆力受损和海马体体积减少的情况最为严重。这些关系在解剖学和神经心理学上是特定的，并且在考虑到脑萎缩后仍然存在。本研究的目的如下：1)首次使用经过验证、可靠和标准化的方法确定糖尿病患者近期记忆缺陷与海马体体积减少之间是否存在特定关联。研究人员将评估相对于匹配的正常对照，患有2型糖尿病的个体以及患有胰岛素抵抗综合征的非糖尿病受试者，现在被美国糖尿病协会（ADA）称为糖尿病前期，是否有学习和记忆障碍，特别是与MRI测量的海马体积减少有关。此外，研究人员将确定2型糖尿病患者是否比糖尿病前期患者在学习和记忆方面有更大的缺陷，以及海马体体积的更大减少。2)为了确定相对于匹配的正常对照，中年2型糖尿病患者对乙酰唑胺（Diamox）的脑血管舒张刺激的血管舒缩反应性是否低于糖尿病前期患者。研究人员还将评估这种血管舒缩反应性的减弱是否与记忆障碍和海马体积减少特别相关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The hippocampus, a brain structure located deep in the temporal lobe, is key for learning and memory. The investigators and several other groups have shown that among normal elderly the MRI-determined volume of the hippocampus is directly related to recent memory performance. The study hypothesizes that there is a specific association between abnormalities in peripheral glucose metabolism and reductions in MRI-derived hippocampal volumes and recent memory performance and that, relative to controls, individuals with type-2 diabetes will have greater hippocampal and memory reductions than those with pre-diabetes. In addition, these relationships will be anatomically and neuropsychologically specific and will remain after accounting for overall brain atrophy. It also postulates that cerebral perfusion reactivity will predict memory performance and hippocampal volumes. Diabetics, who have been shown to have a blunted cerebral vascular response to acetazolamide, will have the largest memory impairments and hippocampal volume reductions. These relationships will be anatomically and neuropsychologically specific and will remain after accounting for brain atrophy. The objectives of the study are as follows: 1) To ascertain for the first time whether there are specific associations between recent memory deficits in diabetes and volume reductions of the hippocampus using validated, reliable, and standardized methods. The investigators will assess whether relative to matched normal controls, individuals with type-2 diabetes as well as non diabetic subjects with insulin resistance syndrome, who are now referred to by the American Diabetes Association (ADA) as having pre-diabetes, have learning and memory impairments that are specifically associated with hippocampal volume reductions measured with MRI. In addition, the investigators will ascertain whether individuals with type-2 diabetes have greater deficits in learning and memory, as well as larger reductions in hippocampal volumes, than prediabetic individuals. 2) To ascertain whether relative to matched normal controls, mid-life individuals with type-2 diabetes show less vasomotor reactivity in response to the cerebral vasodilating stimulus of acetazolamide (Diamox) than those with pre-diabetes. The investigators will also assess whether this diminished vasomotor reactivity is specifically related to memory impairments and hippocampal volume reductions.