The Contribution of Late Onset Unexplained Epilepsy to Cognitive Decline and its Interaction with Vascular and Alzheimer's Disease Pathologies

迟发性不明原因癫痫对认知能力下降的影响及其与血管和阿尔茨海默病病理学的相互作用

基本信息

批准号：
10652547
负责人：
Rani Sarkis
金额：
$ 22.79万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2026-06-30
项目状态：
未结题

项目摘要

Project Summary As life expectancy increases, the burden of seizures in the elderly will increase with up to half of the cases with no identifiable cause termed Late Onset Unexplained Epilepsy (LOUE). Large databases have identified patients with LOUE as having a higher risk of dementia and stroke, but studies focusing on individual patients have been limited. There is a current need to identify the factors underlying LOUE, their impact on cognition and its natural history to develop preventive and therapeutic strategies. The first goal of this project is to determine the burden of the two most common aging pathologies in a cohort of LOUE by assessing the burden of small vessel ischemic disease using MRI and blood biomarkers of Alzheimer’s disease (AD), and how they relate to cognition and neurodegeneration. The second goal is to follow the LOUE cohort over a 3-year period to determine whether the burden of the pathologies increases when someone has seizures and leads to accelerated cognitive decline and neurodegeneration. Through a junior investigator grant funded by the American Epilepsy Society, I have started recruiting a cohort of 40 subjects with LOUE for cross-sectional analyses. As part of the proposed K23, I will expand this cohort to 100 subjects and follow it longitudinally. A control group will consist of subjects from the Harvard Aging Brian Study, an NIH funded study following cognitively normal (at enrollment)older adults with clinical assessments, fluid biomarkers, and multimodal neuroimaging, of which my mentor, Dr. Gad Marshall, has been a co-investigator since its inception. Findings from this study can be applied to other diseases where seizures are a common comorbidity such as Alzheimer’s disease. My training will rely on the mentorship of Dr. Marshall (an expert in AD and aging) and Dr. Page Pennell (an expert in epilepsy), as well as an advisory committee of world leaders in the fields of AD biomarkers (Dr. Dennis Selkoe), neuroimaging (Dr. Steven Stufflebeam), neuropsychology (Dr. Rebecca Amariglio), vascular related cognitive impairment (Dr. Anand Viswanathan), and statistical analysis of longitudinal studies (Dr. Joseph Locascio). During the training period, I will gain expertise in neuroimaging analysis, the implementation of longitudinal studies in an elderly cohort, and the statistical analysis of longitudinal data. The institutional resources available through Brigham and Women’s Hospital, Massachusetts General Hospital, Harvard Medical School, and Harvard School of Public Health are world class and will support my career development in an environment that can foster high impact contributions. Upon successful completion of the project, I will be well positioned to launch a career as an independent investigator examining the interactions of seizures, neurodegeneration, cerebrovascular disease and cognition.

项目摘要随着预期寿命的提高，随着癫痫发作的燃烧，随着多达一半的案件的燃烧将增加没有可识别的原因被称为迟发发病无法解释的癫痫（Loue）。大数据库已经确定 Loue患者患痴呆和中风的风险更高，但研究重点是个别患者受到限制。目前有必要确定路易的因素，它们对认知的影响及其自然历史以制定预防和治疗策略。该项目的第一个目标是确定队列中两种最常见的衰老病的燃烧通过使用MRI和血液生物标志物评估小血管缺血性疾病的伯恩的伯恩阿尔茨海默氏病（AD）及其与认知和神经变性的关系。第二个目标是在3年的时间内遵循Loue队列，以确定病理的燃烧是否增加当某人癫痫发作并导致认知能力下降和神经退行性加速时。通过一个由美国癫痫学会资助的初级调查员赠款，我已经开始招募40个队列 Loue的受试者进行横断面分析。作为拟议的K23的一部分，我将将此队列扩展到100 主题并纵向遵循它。对照组将由哈佛老化的Brian研究的受试者组成， NIH资助的研究是在认知正常（注册）老年人进行临床评估，流体的一项研究我的心理Gad Marshall博士是生物标志物和多模式神经影像学自成立以来。这项研究的发现可以应用于癫痫发作的其他疾病合并症，例如阿尔茨海默氏病。我的培训将依靠Marshall博士（广告和老化专家）和Page Pennell博士的心态（一个癫痫的专家）以及广告生物标志物领域的世界领导人咨询委员会（博士 Dennis Selkoe），神经影像学（Steven Stufflebeam博士），神经心理学（Rebecca Amariglio博士），血管相关认知障碍（Anand Viswanathan博士）和纵向研究的统计分析（博士约瑟夫·洛克西奥（Joseph locascio））。在培训期间，我将获得神经影像学分析的专业知识，该实施纵向研究中的纵向研究以及纵向数据的统计分析。机构哈佛大学马萨诸塞州总医院的杨百翰和妇女医院可用的资源医学院和哈佛公共卫生学院是世界一流的，将支持我的职业发展在可以促进高影响力贡献的环境中。成功完成项目后，我将良好的职业生涯是一名独立调查员，研究了癫痫发作的互动，神经变性，脑血管疾病和认知。