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

癫痫是第四种最常见的神经系统疾病，给医疗保健系统造成的损失约为15.5美元 每年数十亿美元，并对生活质量产生负面影响。癫痫的发病率和流行率在以下几年达到高峰 55岁--这一群体特别容易受到认知和大脑老化加速的影响，这使他们处于 增加进行性神经退行性疾病的风险，包括阿尔茨海默病(AD)。考虑到 美国人口中增长最快的部分是55岁以上的成年人，这一数字 在接下来的几十年里，患有癫痫的成年人将急剧增加，呈现出一个主要的 公共卫生问题。因此，迫切需要对老年人的认知和脑老化进行研究。 成人癫痫，确定加速衰老的潜在机制，并针对可改变的危险因素 可以防止或减轻认知衰退和痴呆症的进展。我们提出了第一个纵向， 老年癫痫患者(55-90岁)认知和脑老化的多点调查 确定加速衰老的血管、遗传、生物标志物和人口统计学危险因素。我们会 通过获得最先进的神经成像、全面的神经心理学、血管 100例颞叶癫痫和额叶癫痫患者的风险、遗传和生物标志物数据 (FLE)来自三个地理和种族/民族多元化的癫痫中心。我们将跟踪这些患者 纵向检查他们在5年内的成像和认知轨迹，并将他们的轨迹与 100例轻度认知功能障碍(MCI)患者和100例正常老年对照组。然后我们将研究 血管、遗传(载脂蛋白4)和脑脊液生物标记物(即淀粉样蛋白β和tau)风险的影响 关于认知衰退的概况，并确定增加发展为痴呆症风险的基线因素。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 与MCI的老化程度相当。我们认为，血管风险增加和AD的存在- 相关的病理学将奠定大脑加速老化(即，区域性)之间的联系 易受伤害患者的症状包括脑白质萎缩、脑白质损伤和低灌注率)和认知能力下降。 这些目标与2014年NINDS癫痫研究基准一致，该基准将限制或 预防癫痫发作的不良后果及其终生治疗。它们还与 AD/阿尔茨海默病痴呆相关痴呆(ADRD)研究的目标是确定风险因素(即， 癫痫)可导致痴呆症。目前的项目对公共卫生有很大的影响，因为它 旨在确定认知能力下降的个体预测因素，有助于预防残疾和进展为 痴呆症，这将对病人护理产生直接和持续的影响。此外，这笔赠款将 探索阿尔茨海默病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.