Late-onset Epilepsy and Cognition

项目总结/摘要 癫痫发作在老年人中比在生活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），许多病例没有已知的病因。该提案假设 晚发性癫痫（LOE;癫痫开始于60岁或更晚，在没有中风或其他确定的 原因）与认知能力下降和预先存在的神经病理学如淀粉样蛋白沉积有关;即， LOE可能是未来认知障碍和痴呆的标志物。该研究将使用来自 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 作为该补助金的一部分，招募了一批新的人员（目标3和4）。具体目的是：1）检验假设， 晚发性癫痫（LOE）与认知能力下降相关，随后发生MCI或 痴呆2)检验Aβ 42/40比值是否与LOE相关。3)以确定是否有 临床鉴定的LOE的认知得分低于没有LOE的个体。4)（【探索性】）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 在LOE患者中的表现。定义LOE是否与以下风险升高相关： 未来的认知障碍可以让患者更早地进行干预，这可能有助于减缓未来的认知障碍。 认知能力下降这是一份申请指导病人为导向的研究职业发展奖 （K23）。拟议项目的总体培训目标是为候选人提供技能， 必须成为一个独立的研究人员在癫痫有关的老化。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的培训 研究;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经验培训;并推进专业 发展准备稿件和在会议上发言的技能。职业发展计划 包括约翰霍普金斯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;老龄化的生物统计学和流行病学研讨会; AD研讨会 病理生理学和研究;出席/出席国家会议。候选人的初选 任命是在约翰霍普金斯神经科，一个非常支持的环境， 初级调查员成功转型为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.