Effects of vascular risk factors on risk for dementia and stroke after late-onset epilepsy (EpilepsyCOG)

血管危险因素对迟发性癫痫 (EpilepsyCOG) 后痴呆和中风风险的影响

• 批准号: 10651728
• 负责人: Hyunmi Choi
• 金额: $ 78万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10651728
• 关键词: Address; Adult; Affect; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Antiepileptic Agents; Awareness; Benefits and Risks; Biological; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Caring; Cerebrovascular Trauma; Classification; Clinical; Clinical Trials; Cognitive; Cohort Studies; Data; Dementia; Diabetes Mellitus; Diagnosis; Elderly; Epilepsy; Ethnic Origin; Event; Funding; Future; Goals; Hyperlipidemia; Hypertension; Impaired cognition; Incidence; Individual; Institute of Medicine (U.S.); Intervention; Intervention Trial; Knowledge; Magnetic Resonance Imaging; Measures; Memory; Modeling; Neurologic; Neurological outcome; Participant; Patients; Persons; Play; Population; Practice Guidelines; Prevention Guidelines; Prevention strategy; Prospective, cohort study; Race; Reduce health disparities; Reporting; Research; Resources; Risk; Risk Assessment; Risk Estimate; Risk Marker; Risk Reduction; Role; Seizures; Sex Differences; Smoking; Specific qualifier value; Stroke; Testing; Treatment Factor; United States National Institutes of Health; Vascular Diseases; Work; age group; aged; brain health; cardiovascular disorder risk; cardiovascular risk factor; clinical care; clinical practice; cognitive ability; cohort; data harmonization; dementia risk; ethnic diversity; executive function; experience; high risk; human old age (65+); improved; individualized medicine; innovation; models and simulation; nervous system disorder; novel; peer; post stroke; preservation; prevent; risk mitigation; risk prediction; risk prediction model; sex; simulation; treatment strategy; vascular risk factor

Project Summary Preserving cognitive ability and brain health is a salient concern of older adults. Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) and stroke disproportionately affect late-onset epilepsy (LOE), defined as LOE diagnosed at ages ≥65. Persons with LOE are 2 to 3 times more likely to subsequently experience AD/ADRD and stroke compared to those without LOE. However, current clinical practice in LOE focuses primarily on seizure control, without any practice guidelines specifying how to mitigate risks for subsequent AD/ADRD and stroke. Preserving the best possible brain health will require integrating accurate risk assessment and effective prevention strategies into epilepsy management. Our main hypothesis is that LOE is an early clinical manifestation—a marker—of an excess burden of pre-epilepsy vascular risk factors (VRFs) and subclinical or covert vascular brain injury (VBI). In some patients, LOE may be the first manifestation of vascular disease. Our hypothesis is supported by our prior work, as well as those of others, that show that (a) VRFs are significant contributors to cognitive decline, AD/ADRD, and stroke, (b) VRFs are associated with LOE, and (c) the effects of VRFs on cognitive decline and stroke are stronger in the presence of epilepsy. Consequently, existing risk prediction algorithms for AD/ADRD and stroke/cardiovascular disease (CVD) may underestimate risk in individuals with LOE, failing to identify those who would benefit from aggressive vascular risk reduction. We propose an unprecedented effort to leverage and pool individual participant data from six NIH-funded US-based prospective cohort studies, because no single cohort study will be large enough to test our main hypothesis. Our objectives in this application are to rigorously investigate relationships of LOE and pre-epilepsy VRFs with cognitive decline and characterize potential biological mechanisms, develop risk prediction algorithms for AD/ADRD and stroke/CVD that accurately estimate risk in the setting of LOE, and integrate LOE into a microsimulation modeling paradigm for testing the effects of VRF interventions in clinical trials. We will pursue three Specific Aims: (1) Quantify the association of LOE with cognitive decline, identify the roles of pre-epilepsy VRFs and MRI-defined covert VBI in this association, and explore differences by sex and race/ethnicity. (2) Assess whether LOE, as a novel risk marker of covert VBI, changes predicted risks for AD/ADRD and stroke/CVD when incorporated into established risk prediction algorithms. (3) Using microsimulation, quantify the incremental value of risk/benefit-based tailored treatment, in which treatment decisions are guided by individual predicted event risk, over a traditional treat-to-target approach, in which the treatment goal is to reduce VRF measures to specific levels, on rates of AD/ADRD and stroke/CVD after LOE. Successful completion of this proposal will propel clinical care models for LOE to consider accurate vascular risk assessment/treatment.

项目概要 保持认知能力和大脑健康是老年人和阿尔茨海默病患者的一个突出问题。 阿尔茨海默病相关痴呆 (AD/ADRD) 和中风对迟发性癫痫的影响尤为严重 (LOE)，定义为年龄≥65 岁时诊断出 LOE 的人随后罹患 LOE 的可能性高出 2 至 3 倍。 与没有 LOE 的人相比，有 AD/ADRD 和中风的经历 然而，目前的 LOE 临床实践。 主要侧重于癫痫发作控制，没有任何实践指南具体说明如何减轻癫痫发作的风险 保持最佳的大脑健康需要准确整合随后的 AD/ADRD 和中风。 我们的主要假设是癫痫管理的风险评估和有效的预防策略。 LOE 是一种早期临床表现，是癫痫前血管危险因素负担过重的一个标志 (VRF) 和亚临床或隐性血管性脑损伤 (VBI) 在某些患者中，LOE 可能是首先发生的。 我们的假设得到了我们以及其他人之前的工作的支持， 表明 (a) VRF 是导致认知能力下降、AD/ADRD 和中风的重要因素，(b) VRF 是 与 LOE 相关，并且 (c) VRF 对认知能力下降和中风的影响在存在时更强 经测试的 AD/ADRD 和中风/心血管疾病的现有风险预测算法。 (CVD) 可能会低估患有 LOE 的个体的风险，无法识别那些将从中受益的人 我们建议采取前所未有的努力来利用和汇集个人。 参与者数据来自 NIH 资助的六项美国前瞻性队列研究，因为没有任何一项队列研究能够 足够大以检验我们的主要假设。我们在此应用中的目标是严格调查。 LOE 和癫痫前 VRF 与认知能力下降的关系以及潜在生物学特征 机制，开发 AD/ADRD 和中风/CVD 的风险预测算法，准确估计以下疾病的风险 LOE的设置，并将LOE集成到微观仿真建模范式中以测试VRF的效果 我们将追求三个具体目标：(1) 量化 LOE 与临床试验的关联。 认知能力下降，确定癫痫前期 VRF 和 MRI 定义的隐性 VBI 在这种关联中的作用，以及 (2) 评估 LOE 是否作为隐性 VBI 的新风险标记， 当纳入既定风险预测时，AD/ADRD 和中风/CVD 的预测风险会发生变化 (3) 使用微观模拟，量化基于风险/收益的定制治疗的增量价值， 与传统的目标治疗相比，哪些治疗决策以个体预测事件风险为指导 方法，其中治疗目标是将 VRF 措施降低到 AD/ADRD 发生率和 LOE 后的中风/CVD 的成功完成将推动 LOE 的临床护理模式。 考虑准确的血管风险评估/治疗。