Noninvasive Stimulation to Improve Hippocampal-Dependent Memory in Older Adults

描述（由申请人提供）：记忆障碍是健康老年人以及患有与年龄相关的神经退行性疾病（如阿尔茨海默病和轻度认知障碍（MCI））的老年人面临的主要挑战。不幸的是，目前还没有可靠和强大的治疗方法来改善老年人的记忆能力。该项目的目标是更好地理解和改善由调查小组开发的记忆障碍的新的潜在治疗方法。这一过程涉及对记忆所必需的海马脑网络的非侵入性刺激，被称为“海马刺激”。“我们之前已经证明，Hipp-Stim可以在年轻健康个体中产生海马网络和关联（海马依赖）记忆的强大和持久的增强。目前的建议是在健康的老年人和MCI患者中测试疗效和作用机制。将在海马依赖性记忆测试和海马网络功能的脑成像测量中观察刺激的影响，所述海马网络功能与记忆能力相关。将使用假手术对照、双盲实验设计，以确保治疗效果对刺激具有特异性。此外，全面的认知评估将测试刺激效应对记忆的选择性，神经成像分析将测试刺激效应对海马脑网络的选择性。将根据个人日常生活活动的执行能力和满意度的变化评估记忆性能的改善，以确定改善记忆对生活质量的影响。通过使用各种假设驱动的刺激强度、频率和传递位置进行Hipp-Stim实验，我们将确定对记忆能力、海马网络功能和生活质量产生最大积极影响的最佳参数。一组MCI患者将使用最佳刺激参数接受治疗，以确定Hipp-Stim是否对这种情况有效。所有的实验都涉及对海马依赖性记忆表现和海马脑网络功能的复杂评估。因此，这些发现将深入了解刺激效应的知识，从而促进对老年人记忆相关大脑区域的相关作用机制的更好理解。这项研究的见解可以推动对年龄相关的记忆障碍及其非侵入性刺激治疗的理解，同时还可以产生新的方法来对抗年龄相关和神经退行性记忆能力丧失。

DESCRIPTION (provided by applicant): Memory impairment is a major challenge for healthy older adults as well as those with age-related neurodegenerative diseases such as Alzheimer's disease and Mild Cognitive Impairment (MCI). Unfortunately there are no current treatments that reliably and robustly improve memory abilities for older adults. The goal of this project is to better understand and to improve a new potential treatment for memory impairment developed by the investigative team. This procedure involves noninvasive stimulation of the hippocampal brain network necessary for memory, and is called "Hipp-Stim." We have previously shown that Hipp-Stim can produce robust and lasting enhancement of the hippocampal network and associative (hippocampal-dependent) memory in young healthy individuals. The current proposal is to test efficacy and mechanisms of action in healthy elderly adults and in MCI patients. The effects of stimulation will be observed on tests of hippocampal- dependent memory and on brain imaging measures of hippocampal network function obtained in relation to memory capabilities. Sham-controlled, double-blind experiment designs will be used to ensure that treatment effects are specific to stimulation. Furthermore, comprehensive cognitive assessments will test selectivity of stimulation effects to memory, and neuroimaging analyses will test selectivity of stimulation effects to hippocampal brain networks. Improvements in memory performance will be assessed in relation to changes in individual's ability to perform and satisfaction with activities of daily living, in order to identify ramifications of improved memory for life quality. By performing Hipp-Stim experiments using a variety of hypothesis-driven stimulation intensities, frequencies, and delivery locations, we will determine optimal parameters for producing the greatest positive effects on memory ability, hippocampal network function, and life quality. A group of individuals with MCI will receive treatment using the optima stimulation parameters in order to determine if Hipp-Stim is effective for this condition. All experiments involve sophisticated assessments of hippocampal- dependent memory performance and hippocampal brain network function. The findings will thus deeply inform knowledge of stimulation effects and therefore foster better understanding of relevant mechanisms of action on memory-related brain regions in older adults. Insights from this research could propel understanding of age- related memory impairment and its treatment by noninvasive stimulation, while also producing new methods to combat age-related and neurodegenerative loss of memory abilities.