PREDICTORS OF COGNITIVE DECLINE IN NORMAL AGING

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。这项研究的目的是确定一个可靠的标志物，预测老年人的认知障碍和进行性脑损伤。具体来说，海马的嗅周和嗅内皮层的萎缩将通过MRI来评估，作为海马萎缩和记忆衰退的早期标志。研究两组医学上健康的老年受试者；一组将是ApoE4等位基因的携带者。第三组是20-30岁的正常健康志愿者。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、18个月和36个月进行评估。将在18个月和36个月时进行核磁共振成像以评估海马病理。在这一人群中，我们将检验以下假设：1)在阿尔茨海默氏症的高危人群中，海马的萎缩是否存在时间序列，在海马体积减少之前，海马体积减少先于颞叶萎缩？2)脑皮层长度是否可以作为纵向记忆的预测指标，是否可以将患者分为正常和轻度认知障碍？3)在携带ApoE4等位基因的人群中，基线海马萎缩的证据是否预示着更大的记忆衰退？这项研究的发现可能会提高我们检测阿尔茨海默病（AD）风险受试者的能力。迄今为止的结果已经证明了连续脑成像和图像处理在监测导致轻度认知障碍（MCI）和AD的记忆衰退的早期过程中的重要性。

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 aim of this research is to identify a reliable marker that predicts cognitive impairment and progressive brain damage in the elderly. Specifically, atrophy of the perirhinal and entorhinal cortices of the hippocampus will be evaluated by MRI as an early marker of hippocampal atrophy and memory decline. Two groups of medically healthy elderly subjects will be studied; one group will be carriers of the ApoE4 allele. A third group will be normal healthy volunteers 20-30 years of age. Clinical evaluations, a neuropsychological battery and Alzheimer's-associated cognitive deficits will be evaluated at baseline, 18 and 36 months. MRIs will be done at 18 and 36 months to evaluate hippocampal pathology. Using this population, the following hypotheses will be tested: 1) In those at risk for Alzheimer¿¿s, is there a temporal sequence of atrophy of the hippocampus, with EC length change preceding hippocampal volume loss, which precedes temporal lobe atrophy? 2) Is EC length a predictor of longitudinal memory, and can this be used to classify patients into normal and minimally cognitively impaired? 3) In those carrying the ApoE4 allele, does evidence of baseline hippocampus atrophy predict a greater memory decline? Findings from this study may enhance our ability to detect subjects at risk for Alzheimer¿¿s disease (AD). Results thus far have demonstrated the importance of serial brain imaging and image processing in monitoring the early course of memory decline leading to mild cognitive impairment (MCI) and AD.