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.

癫痫会影响超过200万美国人，是第四大常见的神经系统疾病。尽管 许多患者长期缓解，终身慢性癫痫与认知能力有关， 精神病和躯体合并症以及表征良好的神经映射负担。最近，有 人们对普通人群认知和大脑衰老的疾病非常感兴趣； 但是，对于患有慢性癫痫的老龄化患者，对这个问题的系统研究很少。我们 假设长时间暴露于癫痫病，并且无数并发症加速了大脑和认知 老化。特定目的1：表征暗示慢性局灶性脑衰老加速脑衰老的生物标志物 使用高级PET/MR方法。我们假设PET/MR生物标志物对脑衰老敏感（例如， 增加β淀粉样蛋白沉积，形态变化，功能和结构连通性的变化， 微观结构完整性降低，代谢降低（FDG-PET）和血管完整性降低） 与年龄匹配的对照相比 年龄加速的大脑衰老。特定目标2：表征加速的其他风险和弹性因素 慢性癫痫中的大脑和认知衰老生物标志物。我们假设与年龄有关的神经影像学 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，我们期望认知结果不良的风险因素，包括血管，社会经济， 生活方式在癫痫中更为普遍，与年龄相关的认知和神经影像有关 生物标志物。特定目标3：确定慢性TLE中生物标志物的时间序列，这表明 大脑和认知衰老，使我们能够对导致加速衰老的机械级联反应进行建模。我们 将提供重要的新机械证据，以表征慢性TLE对大脑的后果和 认知衰老并确定特定的神经影像和行为特征，风险和韧性因素 可能对衰老过程具有保护性（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