PET/MR Correlates of Accelerated Aging in Chronic Epilepsy

慢性癫痫加速衰老的 PET/MR 相关性

• 批准号: 10580787
• 负责人: Alan Blair McMillan
• 金额: $ 60.94万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580787
• 关键词: Acceleration; Adopted; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease model; American; Amyloid beta-Protein; Angiography; Anticonvulsants; Behavioral; Biological Markers; Blood Vessels; Body mass index; Brain; Categories; Chronic; Clinical; Cognition Disorders; Cognitive; Cognitive aging; Deposition; Disease remission; Education; Elderly; Epilepsy; Event; Exposure to; Family history of; Functional Magnetic Resonance Imaging; Gender; General Population; Genetic; Image; Insulin Resistance; Language; Lesion; Life Style; Lipids; Magnetic Resonance Imaging; Measures; Mediating; Medical; Memory; Metabolism; Methods; Modeling; Morphology; Myelin; Neurites; Outcome; Partial Epilepsies; Patients; Perfusion; Persons; Physical Fitness; Population; Positron-Emission Tomography; Premature aging syndrome; Process; Proteins; Recording of previous events; Rest; Risk; Risk Factors; Seizures; Senile Plaques; Severities; Socioeconomic Status; Speed; Statistical Models; Structure; Techniques; Temporal Lobe Epilepsy; Testing; Thick; Vocation; Work; abeta deposition; age related; aging brain; apolipoprotein E-4; arterial spin labeling; brain metabolism; brain morphology; cerebral microbleeds; cohort; comorbidity; connectome; density; executive function; experience; fluorodeoxyglucose positron emission tomography; gray matter; imaging biomarker; interest; lifestyle factors; middle age; morphometry; nervous system disorder; neuroimaging; neuroimaging marker; novel; patient population; perfusion imaging; premature; protective factors; regional difference; resilience factor; sociodemographic factors; socioeconomics; therapy duration; white matter

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.

癫痫症影响着超过 200 万美国人，是第四大常见的神经系统疾病。尽管 许多患者经历长期缓解，终身慢性癫痫与认知、 精神和躯体合并症以及明确的神经影像学负担。近来，有 人们对普通人群的认知障碍和大脑衰老问题非常感兴趣和关注； 然而，对于老年慢性癫痫患者的这个问题还没有进行系统的研究。我们 假设长期接触癫痫及其多种并发症会加速大脑和认知能力的发展 老化。具体目标 1：表征慢性局灶性癫痫中提示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 生物标志物对大脑衰老敏感（例如， β淀粉样蛋白沉积增加、形态变化、功能和结构连接的变化、 显微结构完整性降低、新陈代谢降低（FDG-PET）和血管完整性降低） 与年龄匹配的对照组相比，慢性局灶性癫痫患者队列中的这一比例更高，因此表明 年龄加速大脑老化。具体目标 2：描述加速的其他风险和复原力因素 慢性癫痫的大脑和认知衰老生物标志物。我们假设与年龄相关的神经影像学 生物标志物将预测慢性局灶性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佳的风险因素包括血管、社会经济、 和生活方式在癫痫中更为普遍，并与年龄相关的认知和神经影像学相关 生物标志物。具体目标 3：确定慢性 TLE 中指示的生物标志物的时间序列 大脑和认知衰老使我们能够模拟导致加速衰老的机制级联。我们 将提供重要的新机制证据，描述慢性 TLE 对大脑和 认知老化并确定特定的神经影像和行为特征、风险和复原力因素 可能对衰老过程有保护作用（或有害）。

项目成果

BCI-FES With Multimodal Feedback for Motor Recovery Poststroke.

• DOI: 10.3389/fnhum.2022.725715
• 发表时间: 2022
• 期刊: Frontiers in human neuroscience
• 影响因子: 2.9

Alterations in white matter microstructural properties after lingual strength exercise in patients with dysphagia.

• DOI: 10.1097/wnr.0000000000001796
• 发表时间: 2022-06-08
• 期刊: Neuroreport
• 影响因子: 1.7

T1-/T2-weighted ratio reveals no alterations to gray matter myelination in temporal lobe epilepsy.

• DOI: 10.1002/acn3.51653
• 发表时间: 2023-11
• 期刊: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
• 影响因子: 5.3
• 作者: Denis, Colin;Dabbs, Kevin;Nair, Veena A.;Mathis, Jedidiah;Almane, Dace N.;Lakshmanan, Akshayaa;Nencka, Andrew;Birn, Rasmus M.;Conant, Lisa;Humphries, Colin;Felton, Elizabeth;Raghavan, Manoj;Deyoe, Edgar A.;Binder, Jeffrey R.;Hermann, Bruce;Prabhakaran, Vivek;Bendlin, Barbara B.;Meyerand, Mary E.;Boly, Melanie;Struck, Aaron F.
• 通讯作者: Struck, Aaron F.

The presence, nature and network characteristics of behavioural phenotypes in temporal lobe epilepsy.

• DOI: 10.1093/braincomms/fcad095
• 发表时间: 2023
• 期刊: BRAIN COMMUNICATIONS
• 影响因子: 4.8
• 作者: Struck, Aaron F.;Garcia-Ramos, Camille;Nair, Veena A.;Prabhakaran, Vivek;Dabbs, Kevin;Boly, Melanie;Conant, Lisa L.;Binder, Jeffrey R.;Meyerand, Mary E.;Hermann, Bruce P.
• 通讯作者: Hermann, Bruce P.

Multi-shell connectome DWI-based graph theory measures for the prediction of temporal lobe epilepsy and cognition.

基于多壳连接体 DWI 的图论测量用于预测颞叶癫痫和认知。

• DOI: 10.1093/cercor/bhad098
• 发表时间: 2023
• 期刊: Cerebral cortex (New York, N.Y. : 1991)
• 作者: Garcia-Ramos,Camille;Adluru,Nagesh;Chu,DanielY;Nair,Veena;Adluru,Anusha;Nencka,Andrew;Maganti,Rama;Mathis,Jedidiah;Conant,LisaL;Alexander,AndrewL;Prabhakaran,Vivek;Binder,JeffreyR;Meyerand,MaryE;Hermann,Bruce;Struck,Aaron
• 通讯作者: Struck,Aaron