CLINICAL CORRELATES OF LONGITUDINAL PET CHANGES IN ALZHEIMER'S DISEASE

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。本研究将尝试使用FDG-PET识别临床前阿尔茨海默病（AD）记忆和大脑退化的最早预测因素。该假说认为，内嗅皮层葡萄糖代谢的纵向减少预示着轻度认知障碍的发生。将对两组医学上健康的老年人进行研究：一组有记忆衰退的迹象。第三组是20-30岁的正常健康志愿者。对于第1组和第2组，临床评估，神经心理学测试和阿尔茨海默病相关的认知缺陷将在基线和36个月时进行评估。将在基线和36个月时进行PET和MRI检查以评估海马病理（18个月时也进行MRI检查）。利用这一人群，我们将检验以下假设：1)肠嗅皮质糖代谢是否预示神经心理表现的下降？2)在观察高血糖诱导的正常而非AD患者葡萄糖代谢和记忆增加的基础上，海马葡萄糖转运减少（在稳态高血糖和正常血糖下评估）是否预示着进行性脑退化？这项研究可能有助于发现有AD风险的受试者。

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. This study will attempt to identify the earliest predictors of memory and brain deterioration in preclinical Alzheimer's disease (AD) using FDG-PET. The hypothesis is that longitudinal reductions in glucose metabolism in the entorhinal cortex predict the onset of minimal cognitive impairment. Two groups of medically healthy elderly will be studied: one group will have evidence of memory decline. A third group will be normal healthy volunteers 20-30 years of age. For groups 1&2, clinical evaluations, a neuropsychological battery and Alzheimer's-associated cognitive deficits will be evaluated at baseline and at 36 months. PET and MRI will be performed at baseline and at 36 months to evaluate hippocampal pathology (MRI also at 18 months). Using this population, the following hypotheses will be tested: 1) Does enterorhinal cortex glucose metabolism predict decline in neuropsychological performance? 2) On the basis of observation of hyperglycemia-induced increase in glucose metabolism and memory in normal but not in AD, does decreased hippocampus glucose transport (evaluated under steady-state hyperglycemia and euglycemia) predict progressive brain deterioration? This study may help in the detection of subjects at risk for AD.