Functional and Structural Neuroanatomy of Past Remembrance

持续性记忆障碍是脑损伤后最常见的主诉之一，也是 阿尔茨海默病(AD)以及遗忘性轻度认知障碍(aMCI；介于 健康老龄化和阿尔茨海默病)。这些疾病的患病率正在增加，因为40%的退伍军人管理局人口 老年和年龄是AD的最大危险因素。头部损伤还会增加患AD的风险， 近年来，退伍军人脑损伤(及其伴随的记忆后遗症)的发生率有所增加 由于伊拉克和阿富汗战争，已经有好几年了。努力了解的功能和结构的基础 记忆障碍几乎完全集中在新的学习障碍上。对过去的记忆受损 (逆行记忆[Rm]丧失)很少受到关注，尽管这种损害特别严重 毁灭性的(例如，一个人忘记了家庭关系、重要的事件和关于世界的事实)。虽然 新的学习障碍得到了很好的研究，尽管患有MCI和AD的退伍军人对RM的关注较少 表现出严重的红血球丢失。有趣的是，患有MCI的人在新的学习中可能表现出相对轻微的损害 与相对严重的RM丢失相结合，表明检测RM丢失的新工具可以作为 早期估计与阿尔茨海默病发展相关的认知和神经衰退。年长的老兵展示 衰老导致的大脑结构和功能的变化，患有急性脑梗塞的退伍军人表现得更多 大脑的显著变化。我们将研究这两组人的RM，并确定大脑区域(和 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 年长的退伍军人；然后2)确定RM测试是否可以作为一种新颖而独特的认知测量工具 神经改变与MCI的RM丢失相关。随着时间的推移，经过学习，人们认为 海马区及相关结构对记忆提取的支持作用逐渐减弱 前额叶皮质和其他皮质区域逐渐增加(记忆巩固)。这些观察结果 在人类身上通常可以观察到几年甚至几十年，但奇怪的是，在动物身上却可以观察到几天和几周。 拟议的研究将确定RM的神经解剖学在短时间和长时间范围内的情况。在……里面 此外，我们将使用四种神经影像测量来确定相关的神经解剖学(即，2重点是 2个集中于大脑区域之间的连接)。对于更长的时间范围，内存用于 FACTS将在功能脑成像(FMRI)期间进行测试。这些事实将涉及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个事实的过程中测试内存- 比如，提前1小时到1个月学习的三个单词的句子。灰质和白质的测量 结构也将从解剖磁共振成像和扩散张量成像获得， 分别进行了分析。为了确定结构变化与RM的准确性相关的区域，我们将确定 脑结构(灰质和白质)测量与大脑中隔核表现的相关性 测试。脑功能的测量将从与任务相关的功能磁共振活动和与任务相关的功能磁共振获得 功能连接。为了确定函数与RM相关的区域，我们将确定 大脑活动和大脑连通性会随着记忆年龄的增长而变化。接下来，我们将询问哪些调查结果 这两个时间框架的结构和功能都是共同的。然后，我们将确定大脑区域是否重要 对于认知正常的退伍军人来说，老年退伍军人在患有MCI的退伍军人中存在功能障碍或受损。最后，为了 开发一个实用的RM测试，我们将确定最能预测遗传的问题的子集， 阿尔茨海默病的神经心理学和神经风险。我们预计，RM测试可以作为一种可靠的 敏感的临床指标用于临床前AD的分期或评估退伍军人的治疗效果 神经退行性疾病，减轻照顾者和退伍军人医疗保健的负担。]

[ 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. ]