Explaining cognitive heterogeneity in temporal lobe epilepsy (TLE): Identifying unique imaging features, health-related risk factors and protective factors in TLE subtypes

项目总结/摘要 颞叶癫痫（TLE）是局灶性癫痫最常见的形式，其特征通常为： 使人衰弱和进行性认知障碍。因此，TLE患者经常报告生活质量差 日常功能受损然而，认知障碍的性质和严重程度存在显著差异。 在TLE患者中观察到的损伤，一些患者表现出全身性损伤， 其他人表现出相对正常的认知能力。尽管众所周知的认知变异性 尽管在患者中观察到这种损害，但很少有研究专注于识别不同的认知障碍， TLE综合征中的表型。此外，对其他与健康有关的风险或 可能导致这种变化的个别因素。与健康相关的风险因素，如血管因素和 代谢生物标志物和可改变的风险因素，如高血压、肥胖、缺乏运动和吸烟 与加速认知老化甚至痴呆症有关。与此相反，个人因素，如高 患病前的智商，更多的教育年限，更高的职业成就和双语能力已经被证明是 提供了一个保护因子，防止神经病理学对认知的影响。鉴于TLE现在被理解为 代表一系列疾病，识别具有相似认知特征的患者组可以提供 对TLE患者个体存在的潜在神经病理学的独特见解， 重要的预后价值。这项拟议的研究将是第一个整合先进神经成像数据的研究， 认知数据，与健康相关的风险因素和保护因素，以努力解开异质性， TLE的认知障碍在这项研究中，我们将根据以下因素识别和定义TLE的认知表型： 语言、记忆、执行功能和运动速度的神经心理学测量的损伤。 然后，我们将研究与每种表型相关的脑网络差异和临床特征。 大脑网络的差异将使用结构和扩散数据进行评估， 基于连接体的新方法。此外，我们将确定重要的健康相关风险因素（即，体重指数， 脉压代用指标、空腹血糖、既往或当前血管疾病史、吸烟史、饮食，以及 锻炼）和保护因素（即，病前智商、教育、职业成就、双语能力）， 缓和脑网络异常和认知功能障碍之间的关系。的最终目标 这项建议是针对美国国家神经疾病和中风研究所（NINDS）的主要 该基准侧重于预防和逆转癫痫合并症。鉴于认知障碍 是TLE和癫痫中最常见和最有问题的合并症， 可能有助于识别那些最有可能发生进行性认知功能障碍和/或术后认知功能障碍的患者。 下降此外，该提案可以通过帮助识别可修改的风险/保护措施来直接满足这一要求。 这些因素可用于制定旨在降低进一步认知能力下降风险的干预措施。

Project Summary/Abstract Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy, and it is often characterized by debilitating and progressive cognitive impairment. As a result, patients with TLE often report poor quality of life and impaired daily functioning. However, there is significant variability in the nature and severity of cognitive impairments observed across patients with TLE, with some patients demonstrating generalized impairment and others demonstrating relatively normal cognitive profiles. Despite the well-known variability in cognitive impairment that is observed across patients, few studies have focused on identifying distinct cognitive phenotypes within the syndrome of TLE. In addition, very little is known about other health-related risk or individual factors that may contribute to this variability. Health-related risk factors such as vascular factors and metabolic biomarkers, and modifiable risk factors such as hypertension, obesity, physical inactivity, and smoking have been linked to accelerated cognitive aging and even dementia. In contrast, individual factors such as high pre-morbid IQ, more years of education, higher occupational attainment, and bilingualism have been shown to offer a protective factor against the effects of neuropathology on cognition. Given that TLE is now understood to represent a spectrum of disorders, identifying groups of patients with similar cognitive profiles may provide unique insight into the underlying neuropathology that exists in individual patients with TLE, which could have important prognostic value. The proposed study will be the first to integrate advanced neuroimaging data, cognitive data, and health-related risk factors and protective factors in an effort to unravel the heterogeneity of cognitive impairment in TLE. In this study, we will identify and define cognitive phenotypes in TLE based on impairment across neuropsychological measures of language, memory, executive function, and motor speed. We will then investigate brain network differences and clinical features associated with each phenotype. Differences in brain networks will be evaluated using structural and diffusion data utilizing both a regional and a novel connectome-based approach. In addition, we will identify important health-related risk factors (i.e., BMI, pulse pressure proxy, fasting glucose, history of past or current vascular disease, history of smoking, diet, and exercise) and protective factors (i.e., pre-morbid IQ, education, occupation attainment, bilingualism) that moderate the relationship between brain network abnormalities and cognitive dysfunction. The ultimate goal of this proposal is to address the National Institutes of Neurological Diseases and Strokes (NINDS) major benchmark focused on the prevention and reversal of comorbidities in epilepsy. Given that cognitive impairment is the most common and problematic comorbidity in TLE and epilepsy in general, the results from this proposal may help identify those at greatest risk for progressive cognitive dysfunction and/or post-operative cognitive decline. Furthermore, this proposal can directly address this request by helping identify modifiable risk/protective factors that may be used to develop interventions targeted at reducing the risk of further cognitive decline.