Late-onset Epilepsy and Cognition

项目摘要/摘要 突发癫痫在老年人中比生命中的任何其他时期都更常见。虽然有些案件是由于 中风或已知的阿尔茨海默病(AD)，许多病例的病因不明。这项提议假定 迟发性癫痫(LOE；癫痫始于60岁或更晚，在没有中风或其他确诊的情况下 原因)与认知能力下降和先前存在的神经病理(如淀粉样蛋白沉积)有关；即， LOE可能是未来认知障碍和痴呆症的标志。这项研究将使用来自 正在进行的社区动脉粥样硬化风险(ARIC)队列研究(目标1和2)以及来自 作为这笔赠款的一部分招募一个新的队列(目标3和4)。具体目的是：1)检验假设 迟发性癫痫(LOE)与认知功能下降以及随后发生的MCI或 痴呆症。2)检测β的42/40比值是否与LOE相关。3)确定个人是否患有 临床确诊的LOE患者的认知得分低于非LOE患者。4)(探索性的)比较 伴和不伴LOE患者的AD生物标志物，以及亚临床癫痫样活动与认知功能的相关性 LOE患者的表现。确定LOE是否与高血压风险升高有关 未来的认知障碍可能允许患者进行更早的干预，这可能有助于延缓未来 认知能力下降。这是一份申请以患者为导向的导师研究事业发展奖的申请书 (K23)。拟议项目的主要培训目标是为应聘者提供技能 有必要成为与衰老相关的癫痫的独立研究人员。具体的培训目标是 获得流行病学和生物统计学方面的高级培训；获得招募和领导队列方面的培训 学习；获得和应用AD病理生理学知识和生物标志物的使用；获得教学和 神经退行性疾病认知评估的体验式培训；并提升专业水平 在准备稿件和在会议上发言方面的发展技能。职业发展计划 包括约翰霍普金斯大学公共卫生学院的生物统计学和流行病学课程；定期 与导师的会议；生物统计学和老龄化流行病学研讨会；AD研讨会 病理生理学和研究；出席/在国家会议上发言。候选人的初选 任命在约翰·霍普金斯大学神经病学系，这是一个非常有支持性的环境 初级调查员成功过渡到独立调查员的良好历史。

PROJECT SUMMARY/ABSTRACT Incident epilepsy is more common in the elderly than at any other time of life. While some cases are due to stroke or known Alzheimer’s disease (AD), many cases have no known etiology. This proposal hypothesizes that late-onset epilepsy (LOE; epilepsy starting at age 60 or later, in the absence of stroke or other identified cause) is associated with cognitive decline and preexisting neuropathology such as amyloid deposition; i.e., LOE may be a marker for future cognitive impairment and dementia. The research will use data from the ongoing longitudinal Atherosclerosis Risk in Communities (ARIC) cohort study (Aims 1 and 2), as well as from a new cohort recruited as part of this grant (Aims 3 and 4). The specific aims are: 1) To test the hypothesis that late-onset epilepsy (LOE) is associated with cognitive decline, and the subsequent development of MCI or dementia. 2) To test whether Aβ 42/40 ratio is associated with LOE. 3) To determine whether individuals with clinically-identified LOE have lower cognitive scores than individuals without LOE. 4) (Exploratory) To compare AD biomarkers in patients with and without LOE, and correlate subclinical epileptiform activity with cognitive performance in patients with LOE. Defining whether there is an association of LOE with an elevated risk of future cognitive impairment could allow patients to have earlier interventions, which may help slow future cognitive decline. This is an application for a Mentored Patient-Oriented Research Career Development Award (K23). The overarching training goal of the proposed project is to provide the candidate with the skills necessary to become an independent researcher in epilepsy related to aging. Specific training goals are to obtain advanced training in epidemiology and biostatistics; to obtain training in recruiting and leading cohort studies; to acquire and apply knowledge of AD pathophysiology and the use of biomarkers; to gain didactic and experiential training in cognitive assessments in neurodegenerative diseases; and to advance professional development skills in preparing manuscripts and presenting at conferences. The career development plan includes classes in biostatistics and epidemiology at the Johns Hopkins School of Public Health; regular meetings with mentors; seminars in biostatistics and the epidemiology of aging; seminars in AD pathophysiology and research; and attending/presenting at national conferences. The candidate’s primary appointment is in the Johns Hopkins Department of Neurology, an extremely supportive environment with a strong history of junior investigators successfully transitioning to independent investigators.