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系统疾病。而 许多患者经历长期缓解，终身慢性癫痫与认知相关， 精神和躯体共病以及特征明确的神经影像学负担。最近， 对一般人群中的认知障碍和脑老化问题有很大的兴趣和关注; 然而，在患有慢性癫痫的老年人中很少有系统的研究。我们 假设长期暴露于癫痫及其无数并发症会加速大脑和认知功能 衰老具体目标1：表征提示慢性局灶性癫痫患者大脑加速老化的生物标志物 使用先进的PET/MR方法。我们假设PET/MR生物标志物对脑老化敏感（例如， 增加的β淀粉样蛋白沉积、形态学变化、功能和结构连接的变化， 降低的微结构完整性、降低的代谢（FDG-PET）和降低的血管完整性）将被 与年龄匹配的对照组相比，慢性局灶性癫痫患者队列中的 大脑加速老化具体目标2：描述加速发展的其他风险和复原力因素 慢性癫痫中的脑和认知老化生物标志物。我们假设年龄相关的神经影像学检查 生物标志物将预测慢性局灶性脑梗死患者认知异常的存在和严重程度。 癫痫此外，我们预计认知结果不良的风险因素，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影像学有关 生物标志物。具体目标3：确定慢性TLE中指示以下情况的生物标志物的时间序列： 大脑和认知老化，使我们能够模拟导致加速老化的机械级联。我们 将提供重要的新的机制证据，表征慢性TLE对大脑的影响， 认知老化，并确定具体的神经影像和行为概况，风险和弹性因素， 可能对老化过程具有保护性（或有害）。

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.