PET/MR Correlates of Accelerated Aging in Chronic Epilepsy

癫痫影响着200多万美国人，是第四大最常见的神经疾病。而当 许多患者经历长期缓解，终生慢性癫痫与认知、 精神和躯体并存，以及典型的神经成像负担。最近，有 在普通人群中对认知障碍和脑老化非常感兴趣和关注； 然而，在老年慢性癫痫患者中，对这一问题的系统研究很少。我们 假设长期暴露在癫痫及其各种并发症中会加速大脑和认知能力 衰老。具体目标1：表征慢性局灶性癫痫脑老化加速的生物标志物 使用先进的PET/MR方法。我们假设对脑老化敏感的PET/MR生物标记物(例如， β淀粉样蛋白沉积增加，形态改变，功能和结构连接性改变， 微结构完整性降低，新陈代谢(FDG-PET)和血管完整性降低) 在慢性局灶性癫痫患者队列中，与年龄匹配的对照组相比，这一点更大，因此表明 年龄加速了大脑的老化。具体目标2：确定加速的其他风险和复原力因素 慢性癫痫的脑和认知老化生物标记物。我们假设与年龄相关的神经成像 生物标志物将预测慢性局灶性疾病患者认知异常的存在和严重程度 癫痫。此外，我们预计认知结果差的风险因素，包括血管、社会经济、 和生活方式在癫痫中更普遍，并与年龄相关的认知和神经成像有关 生物标志物。具体目标3：确定慢性TLE中生物标志物的时间序列，这些生物标志物表明 大脑和认知老化使我们能够模拟导致加速衰老的机械级联反应。我们 将提供重要的新机制证据，表征慢性TLE对大脑和大脑的影响 认知老化，并确定特定的神经成像和行为特征，风险和复原力因素 可能对老化过程起到保护作用(或有害作用)。

Epilepsy affects more than 2 million Americans and is the fourth most common neurological disorder. While many patients experience long-term remission, lifelong chronic epilepsy is associated with cognitive, psychiatric, and somatic comorbidities and a well-characterized neuroimaging burden. Recently, there has been much interest and concern regarding disorders of cognitive and brain aging in the general population; however, there has been little systematic study of this issue in aging persons with chronic epilepsy. We hypothesize that prolonged exposure to epilepsy and its myriad of complications accelerate brain and cognitive aging. Specific Aim 1: Characterize biomarkers suggestive of accelerated brain aging in chronic focal epilepsy using advanced PET/MR methods. We hypothesize that PET/MR biomarkers sensitive to brain aging (e.g., increased beta amyloid deposition, morphological changes, changes in functional and structural connectivity, reduced microstructural integrity, reduced metabolism (FDG-PET), and reduced vascular integrity) will be greater in a cohort of chronic focal epilepsy patients compared to age-matched controls, and thus indicative of age-accelerated brain aging. Specific Aim 2: Characterize other risk and resilience factors for accelerated brain and cognitive aging biomarkers in chronic epilepsy. We hypothesize that age-related neuroimaging biomarkers will predict the presence and severity of cognitive abnormalities in patients with chronic focal epilepsy. Furthermore, we expect risk factors for poor cognitive outcome, including vascular, socioeconomic, and lifestyle to be more prevalent in epilepsy and related to age-related cognitive and neuroimaging biomarkers. Specific Aim 3: Identify the temporal sequence of biomarkers in chronic TLE that are indicative of brain and cognitive aging allowing us to model the mechanistic cascade that leads to accelerated aging. We will provide important new mechanistic evidence characterizing the consequences of chronic TLE on brain and cognitive aging and identify the specific neuroimaging and behavioral profiles, risk and resilience factors that may be protective (or detrimental) to the aging process.