Neuroimaging and Functional Senscence in Aging

衰老过程中的神经影像学和功能感觉

• 批准号: 6479804
• 负责人: NIKOLAOS MAKRIS
• 金额: $ 6.9万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6479804
• 关键词: Macaca mulatta; age difference; animal old age; behavior test; bioimaging /biomedical imaging; biological models; brain imaging /visualization /scanning; brain morphology; electrophysiology; histology; magnetic resonance imaging; male; morphometry; myelin; neuroanatomy; neuroimaging; neurophysiology; neuropsychology; perfusion; postmortem; psychological aspect of aging; tissue /cell preparation

The rhesus monkey is an excellent model for studies of normal aging since brain organization and cognitive capacity are quite similar to humans and the monkey does not get Alzheimer's disease. Additionally monkeys can be studied under controlled conditions, behavioral assessment can be done prior to death and the brain can be optimally preserved without post-mortem delay. Such studies demonstrate age- related cognitive decline with preservation of neurons and synapses but loss and damage to white matter and volumetric loss of white matter in standard MRI scans. But, it is not clear whether loss or damage to myelin is diffuse or localized to specific pathways. Since breakdown in myelin correlates with cognitive decline, it is probably that disruption of corticocortical fiber tracts my contribute to age-related cognitive impairments. A new neuroimaging method, Diffusion Tensor MRI (DT- MRI) has been used for in vivo identification and measurement of long white tracts in the human brain but a major limitation on interpretation of the DT-MRI in humans is the difficulty of validation by post-mortem examination of white matter tracts because of post-mortem delay and immersion fixation. This proposed pilot investigation will adapt to the monkey brain this new DT-MRI method to identify and quantify white matter tracts in young and old monkeys. These monkeys are available to us from an NIH funded Program Project grant which collects behavioral measures of cognitive performance, neurophysiological measures of conduction velocity and then prepares whole hemisphere serial brain sections. These data and spare series of sections will be available for comparisons with the CT-MRI data on specific fiber tracts. To determine their "functional" significance the long corticocortical association pathways will be identified, quantified and age-related changes in volume determined and then correlated with the behavioral and neurophysiological data of the DT-MRI observations. In addition spare series of histological sections will be used to validate the DT-MRI observations with actual white matter and provide the pilot data necessary to seek funding for additional DT-MRI studies of normal aging in both monkeys and humans.

由于脑组织和认知能力与人类非常相似，恒河猴是对正常衰老的研究的绝佳模型，而且猴子没有患阿尔茨海默氏病。 另外，可以在受控条件下研究猴子，行为评估可以在死亡前进行，并且可以在无验尸延迟的情况下最佳地保存大脑。这样的研究表明，与年龄相关的认知能力下降，保存神经元和突触，但在标准MRI扫描中对白质的损失和损害损失以及白质的体积损失。但是，目前尚不清楚髓磷脂的损失或损害是分散的还是局限于特定途径。由于髓磷脂与认知能力下降相关，因此皮质皮质纤维片的破坏可能导致与年龄相关的认知障碍。 一种新的神经影像学方法，扩散张量MRI（DT-MRI）已被用于体内识别和测量人脑中长白色的长白道，但是对人类对DT-MRI的解释的主要局限性是通过POST验证的困难 - 由于事后延迟和浸入固定，对白质区的验证检查。这项提出的试点调查将适应这种新的DT-MRI方法，以识别和量化年轻猴子和老猴子的白质区。这些猴子可以从NIH资助的计划项目赠款中获得，该项目赠款收集了认知性能的行为度量，神经生理学的传导速度测量方法，然后准备整个半球串行脑部切片。 这些数据和备用一系列部分将用于与特定纤维区域的CT-MRI数据进行比较。为了确定其“功能”重要性，将确定，量化和年龄相关的体积变化，并与DT-MRI观察结果的行为和神经生理学数据相关。此外，将使用一系列备用的组织学部分来验证具有实际白质的DT-MRI观察结果，并提供了为猴子和人类正常衰老的其他DT-MRI研究提供必要的试点数据。