Functional and Structural Neuroanatomy of Past Remembrance

过去记忆的功能和结构神经解剖学

• 批准号: 9238578
• 负责人: Christine Nicole Smith
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-10-01 至 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9238578
• 关键词: Affect; Afghanistan; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Anatomy; Animal Testing; Animals; Area; Attention; Brain; Brain Injuries; Brain imaging; Brain region; Caregivers; Clinical; Cognitive; Craniocerebral Trauma; Dementia; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Elderly; Event; Exhibits; Family Relationship; Foundations; Functional Imaging; Goals; Health; Healthcare; Hippocampus (Brain); Hour; Human; Image; Impairment; Incidence; Individual; Injury; Intervention; Iraq; Knowledge; Learning; Lesion; Magnetic Resonance Imaging; Measures; Memory; Memory Loss; Memory impairment; Mental disorders; Methods; Neuroanatomy; Neurodegenerative Disorders; Neurologic; Neuropsychology; Occipital lobe; Parietal Lobe; Participant; Patients; Performance; Population; Positron-Emission Tomography; Prefrontal Cortex; Prevalence; Reporting; Risk; Risk Factors; Role; Scanning; Staging; Structure; Technology; Temporal Lobe; Testing; Thick; Time; Treatment Efficacy; Veterans; War; amnestic mild cognitive impairment; genetic predictors; gray matter; healthy aging; improved; interest; long term memory; memory consolidation; memory retrieval; mild cognitive impairment; neuroimaging; news; normal aging; novel; novel strategies; pre-clinical; prevent; relating to nervous system; repository; success; tool; white matter

[ Persistent memory impairment is one of the most common complaints after brain injury and is the hallmark of Alzheimer's disease (AD) as well as amnestic Mild Cognitive Impairment (aMCI; a transitional stage between healthy aging and AD). The prevalence of these conditions is increasing, as 40% of the VA population is elderly and age is the greatest risk factor for AD. Head injury also increases the risk of developing AD and the incidence of brain injury in Veterans (and the memory sequelae that accompanies it) has increased in recent years due to the Iraq and Afghanistan wars. Efforts to understand the functional and structural substrates of memory impairment have focused almost entirely on impaired new learning. Impaired remembering of the past (retrograde memory [RM] loss) has received little attention even though this impairment is particularly devastating (e.g., one forgets family relationships, important events, and facts about the world). Although impaired new learning is well studied, RM has received less attention even though Veterans with MCI and AD exhibit severe RM loss. Interestingly, individuals with MCI can exhibit relatively mild impairment in new learning in conjunction with relatively severe RM loss, suggesting that a new tool to detect RM loss could serve as an early estimate of cognitive and neural decline associated with the development of AD. Older Veterans exhibit changes in brain structure and function as the result of aging, and Veterans with aMCI exhibit even more significant changes in the brain. We will study RM in these two groups and identify brain regions (and connections between brain regions) where measures of structure and function are related to performance on RM tests. The two goals of the proposal are 1) to identify which brain regions support RM in cognitively normal older Veterans; and then 2) determine if a RM test could serve as a novel and unique gauge of the cognitive and neural changes associated RM loss in MCI. As time passes after learning, it is thought that the role of the hippocampus and related structures in supporting memory retrieval gradually decreases, whereas the role of the prefrontal cortex and other cortical areas gradually increase (memory consolidation). These observations are typically observed across years and decades in humans but, curiously, across days and weeks in animals. The proposed studies will identify the neuroanatomy of RM for both the short and longer time frames. In addition, we will identify the relevant neuroanatomy using four neuroimaging measures (i.e., 2 focusing on brain regions and 2 focusing on connections between brain regions). For the longer time frame, memory for facts will be tested during functional brain imaging (fMRI). The facts will concern 160 notable news events that occurred 1 to 30 years earlier. For the short time frame, memory will be tested during scanning for 320 fact- like, three-word sentences that were learned 1 hour to 1 month earlier. Measures of grey and white matter structure will also be obtained from anatomical magnetic resonance imaging and diffusion tensor imaging, respectively. To identify regions where structural changes correlate with the accuracy of RM, we will identify correlations between measures of brain structure (grey matter and white matter) and performance on the RM tests. Measures of brain function will be obtained from task-related fMRI activity and task-related fMRI functional connectivity. To identify regions where function correlates with RM, we will identify regions where brain activity and brain connectivity change with the age of memory. Next, we will ask which findings for structure and function are common to both time frames. Then, we will determine if the brain regions important for RM in cognitively normal older Veterans are dysfunctional or damaged in Veterans with aMCI. Finally, for developing a practical RM test, we will identify a subset of the questions that best predict genetic, neuropsychological, and neural risk for developing AD. We anticipate that a RM test can serve as a robust and sensitive clinical measure for staging preclinical AD or gauging the efficacy of treatments in Veterans with neurodegenerative disorders and reduce the burden on caregivers and VA Healthcare. ]

[持续性记忆障碍是脑损伤后最常见的症状之一，也是脑损伤的标志。 阿尔茨海默病（AD）以及遗忘型轻度认知障碍（aMCI;阿尔茨海默病（AD）和轻度认知障碍（aMCI）之间的过渡阶段。 健康老化和AD）。这些疾病的患病率正在增加，因为40%的VA人口 老年人和年龄是AD的最大危险因素。头部受伤也会增加患AD的风险， 近年来，退伍军人脑损伤（以及伴随而来的记忆后遗症）的发病率有所增加。 多年来，由于伊拉克和阿富汗战争。努力了解的功能和结构基板的 记忆障碍几乎完全集中在受损的新学习上。对过去的记忆受损 （逆行记忆[RM]丧失）很少受到关注，尽管这种损害特别 破坏性的（例如，一个人忘记了家庭关系、重要事件和关于世界的事实）。虽然 受损的新学习得到了很好的研究，RM受到的关注较少，即使患有MCI和AD的退伍军人 表现出严重的RM损失。有趣的是，MCI患者在新的学习中表现出相对轻微的障碍， 结合相对严重的RM损失，这表明检测RM损失的新工具可以作为 早期评估与AD发展相关的认知和神经衰退。老退伍军人展览 随着年龄的增长，大脑结构和功能发生了变化，而患有aMCI的退伍军人表现出更多 大脑的重大变化。我们将研究这两组的RM，并确定大脑区域（以及 大脑区域之间的连接），其中结构和功能的测量与 RM测试。该提案的两个目标是：1）确定哪些大脑区域支持认知正常的RM 老年退伍军人;然后2）确定RM测试是否可以作为一种新颖而独特的认知量表， 以及MCI中与RM丢失相关的神经变化。随着学习后时间的推移，人们认为， 海马和相关结构在支持记忆提取中的作用逐渐减弱，而海马和相关结构在支持记忆提取中的作用逐渐减弱。 前额叶皮层和其他皮层区域逐渐增加（记忆巩固）。这些观察结果 通常在人类身上观察到数年或数十年，但奇怪的是，在动物身上观察到数天或数周。 拟议的研究将确定RM的神经解剖学的短期和长期的时间框架。在 此外，我们将使用四种神经成像测量（即，2聚焦 脑区域和2个集中于脑区域之间的连接）。对于较长的时间框架，内存为 事实将在功能性脑成像（fMRI）中进行测试。事实将涉及160个值得注意的新闻事件， 发生在1到30年前。在短时间内，将在扫描320个事实期间测试内存- 比如说，三个单词的句子，是在一个小时到一个月前学的。灰色和白色物质的测量 还将从解剖磁共振成像和扩散张量成像获得结构， 分别为了确定结构变化与RM准确性相关的区域，我们将确定 脑结构（灰质和白色物质）测量与RM上的表现之间的相关性 试验.脑功能的测量将从任务相关的功能磁共振成像活动和任务相关的功能磁共振成像获得 功能性连接。为了识别功能与RM相关的区域，我们将识别 大脑活动和大脑连接随着记忆的年龄而变化。接下来，我们将询问哪些发现 这两个时间框架结构和功能是相同的。然后，我们将确定大脑区域是否重要 认知正常的老年退伍军人的RM在患有aMCI的退伍军人中功能障碍或受损。最后针对 开发一个实用的RM测试，我们将确定一个子集的问题，最好的预测遗传， 神经心理学和发展AD的神经风险。我们预计，RM测试可以作为一个强大的， 用于临床前AD分期或评估退伍军人治疗效果的敏感临床指标， 神经退行性疾病，减轻护理人员和VA Healthcare的负担。]