BRain Aging and Cognition in Epilepsy (BRACE): A longitudinal investigation of vascular, genetic, and biomarker risk profiles in elderly patients with epilepsy

癫痫是第四大常见的神经系统疾病，医疗系统花费约 15.5 美元 每年损失数十亿美元，并对生活质量产生负面影响。癫痫的发病率和患病率在 55 岁——这个群体特别容易加速认知和大脑老化，使他们处于 进行性神经退行性疾病的风险增加，包括阿尔茨海默病（AD）。鉴于 美国人口中增长最快的部分是 55 岁以上的成年人， 患有癫痫症的成年人将在未来几十年内急剧增加，这将是一个重大的问题 公共卫生问题。因此，迫切需要描述老年人的认知和大脑衰老特征 患有癫痫的成年人，确定加速衰老的潜在机制，并针对可改变的风险因素 可以预防或减轻认知能力下降和痴呆症的进展。我们提出第一个纵向， 对患有癫痫的老年人（55-90 岁）的认知和大脑衰老进行多点调查 识别加速衰老的血管、遗传、生物标志物和人口统计学风险因素。我们会 通过获得最先进的神经影像学、全面的神经心理学、血管学 100 名颞叶癫痫 (TLE) 和额叶癫痫患者的风险和遗传/生物标志物数据 (FLE) 来自三个地理和种族/民族不同的癫痫中心。我们将跟踪这些患者 纵向检查他们 5 年来的成像和认知轨迹，并将他们的轨迹与 100 名轻度认知障碍 (MCI) 患者和 100 名正常衰老对照。然后我们将检查 血管、遗传（载脂蛋白 4）和脑脊液生物标志物（即淀粉样蛋白 β 和 tau）风险的影响 认知能力下降的概况，并确定增加痴呆症进展风险的基线因素。我们的 科学前提是患有局灶性癫痫的老年人会表现出年龄加速的认知和大脑功能 老化程度与 MCI 中所见的老化程度相当。我们认为血管风险升高和 AD- 相关的病理学将成为大脑加速老化（即区域性老化）之间关联的基础。 萎缩、白质损伤和灌注不足）以及脆弱患者的认知能力下降。 这些目标与 2014 年 NINDS 癫痫研究基准一致，该基准优先考虑限制或 预防癫痫发作的不良后果及其整个生命周期的治疗。他们也符合 AD/阿尔茨海默氏痴呆相关痴呆 (ADRD) 研究目标是识别风险因素（即， 癫痫发作）进展为痴呆。当前的项目对公共卫生具有重大影响，因为它 旨在确定认知能力下降的个体预测因素，这有助于防止残疾和进展 痴呆症，这将对患者护理产生直接和持续的影响。此外，这笔赠款将 探索 AD 和癫痫之间的双向联系，可能会为两者带来治疗机会 疾病和其他衰老障碍。

Epilepsy is the fourth most common neurological disease, costing the healthcare system approximately $15.5 billion annually and negatively impacting quality of life. The incidence and prevalence of epilepsy peaks over the age of 55—a group that is particularly vulnerable to accelerated cognitive and brain aging, placing them at increased risk for progressive neurodegenerative disorders, including Alzheimer's disease (AD). Given that the most rapidly growing segment of the U.S. population is adults over the age of 55, the number of older adults living with epilepsy will dramatically increase over the next several decades, presenting a major public health concern. Therefore, there is a critical need to characterize cognitive and brain aging in older adults with epilepsy, identify underlying mechanisms of accelerated aging, and target modifiable risk factors that would prevent or mitigate cognitive decline and progression to dementia. We propose the first longitudinal, multi-site investigation of cognitive and brain aging in older adults (55-90 years) with epilepsy in efforts to identify vascular, genetic, biomarker and demographic risk factors for accelerated aging. We will accomplish this goal by obtaining state-of-the-art neuroimaging, comprehensive neuropsychological, vascular risk, and genetic/biomarker data on 100 patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) from three geographically and racially/ethnically diverse epilepsy centers. We will follow these patients longitudinally, examine their imaging and cognitive trajectories over 5 years, and compare their trajectories to 100 patients with mild cognitive impairment (MCI) and 100 normal aging controls. We will then examine the influence of vascular, genetic (apolipoprotein 4), and cerebrospinal fluid biomarker (i.e, amyloidβ and tau) risk profiles on cognitive decline and identify baseline factors that increase risk for progression to dementia. Our scientific premise is that older adults with focal epilepsy will show age-accelerated cognitive and brain aging comparable to that seen in MCI. We propose that elevated vascular risk and the presence of AD- associated pathology will underlie the association between accelerated brain aging (i.e, regional atrophy, white matter injury, and hypoperfusion) and cognitive decline in vulnerable patients. These goals are aligned with the 2014 NINDS Benchmarks for Epilepsy Research, which prioritize limiting or preventing adverse consequences of seizures and their treatment across the lifespan. They are also aligned with the AD/Alzheimer's Dementia Related Dementias (ADRD) research goals of identifying risk factors (i.e., seizures) for progression to dementia. The current project has strong implications for public health because it aims to identify individual predictors of cognitive decline that could help to prevent disabilty and progression to dementia, which would have an immediate and sustained impact on patient care. Furthermore, this grant will explore the bi-directional link between AD and epilepsy, would could lead to therapeutic opportunities for both diseases and other disorders of aging.