The effects of cumulative concussion, repetitive head impacts, and comorbid cardiovascular risk factors on MRI metrics of pathological aging and neurobehavioral functioning across the lifespan

累积性脑震荡、重复性头部撞击和合并心血管危险因素对整个生命周期病理性衰老和神经行为功能的 MRI 指标的影响

• 批准号: 10651801
• 负责人: Benjamin L Brett
• 金额: $ 13.22万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10651801
• 关键词: Age; Aging; Anisotropy; Anxiety; Award; Behavior Therapy; Blood Vessels; Brain Concussion; Cerebrovascular Circulation; Child; Craniocerebral Trauma; Cross-Sectional Studies; Data; Data Set; Diet; Diffusion Magnetic Resonance Imaging; Emergency department visit; Exposure to; General Population; Goals; Health; Health behavior; Hybrids; Impaired cognition; Intervention; Life; Longevity; Magnetic Resonance Imaging; Mediating; Mediation; Memory; Mental Depression; Mentors; Mentorship; Methods; Mission; Molecular; Multicenter Studies; Nature; Neurobiology; Neurodegenerative Disorders; Neurologic; Outcome; Pathway interactions; Physical activity; Positioning Attribute; Process; Public Health; Radial; Recording of previous events; Recurrence; Research; Risk; Risk Estimate; Risk Factors; Role; Severities; Site; Sports; Symptoms; Testing; Therapeutic Intervention; Training; United States; United States National Institutes of Health; Validation; White Matter Hyperintensity; Work; advanced analytics; age effect; arterial spin labeling; brain health; burden of illness; cardiovascular risk factor; cohort; comorbidity; contact sports; design; executive function; follow-up; head impact; human old age (65+); improved; innovation; insight; large scale data; mild traumatic brain injury; nervous system disorder; neurobehavioral; neuroimaging; neuropathology; pathological aging; preventive intervention; processing speed; programs; prospective; public health relevance; therapeutic development; therapeutic target; white matter

Project Summary/Abstract (1 page) Exposure to mild traumatic brain injury (mTBI) and repetitive head impacts (RHI) during sport participation has been associated with adverse long-term consequences (e.g., cognitive decline). Research investigating these associations has been limited to cross-sectional studies at single points of the lifespan without consideration of factors that can influence these associations. Greater mTBI/RHI history is associated with cerebral blood flow (CBF) and white matter (WM) abnormalities, even within younger athletes. CBF and WM abnormalities are two indicators of pathological aging and longitudinal decline in the general population. Age and cardiovascular risk factors across the lifespan can influence these abnormalities. The scientific objective of this proposal is to determine the influence of mTBI/RHI on MRI metrics of pathological aging and neurobehavioral function across the lifespan. Our central hypothesis is that mTBI/RHI will be associated with neurobehavioral function and CBF/WM abnormalities, and that the strength of this association is independently influenced by increasing age and the presence of cardiovascular risk factors. The rationale for this project is that determining the influence of mTBI/RHI on MRI metrics of pathological aging and neurobehavioral function across the lifespan, as well as factors that influence this relationship, will provide insight into the process underlying cumulative head injury and neurological decline later in life. Our hypothesis will be tested with two specific and one exploratory aims: 1) Determine the associations between mTBI/RHI and neurobehavioral function across the lifespan and the influence of comorbid cardiovascular risk factors; 2) Determine the associations between mTBI/RHI and MRI metrics of pathological aging across the lifespan and the influence of comorbid cardiovascular risk factors; Exploratory) Examine if MRI metrics of pathological aging mediate the association between cumulative mTBI/RHI and neurobehavioral function across the lifespan. To establish an independent research program that identifies the mechanisms by which mTBI/RHI can result in long-term neurological disease burden, the training objective of this proposal is to receive expert training/mentorship in a) the analysis and interpretation of neuroimaging data, b) the cumulative effects of aging and cardiovascular risk factors on long-term brain health and function, and c) the molecular mechanisms and progression of neuropathology as a consequence of mTBI/RHI. We will employ an innovative lifespan approach by leveraging data from four large-scale, prospective, multi-center studies of athletes across several decades of life. Harmonization of several mentor- directed, large-scale multisite datasets of athletes will allow a hybrid prospective, cross-sectional design. We will utilize advanced analytical approaches to examine the potential influence of aging and comorbid cardiovascular risk factors on the associations between mTBI/RHI with MRI metrics of pathological aging and long-term neurobehavioral changes. This work is significant in that it will inform methods for identifying those at risk for decline, improve risk estimates of long-term outcomes, and inform therapeutic targets for intervention.

项目摘要/摘要（1页） 体育参与期间暴露于轻度创伤性脑损伤（MTBI）和重复的头部影响（RHI） 与不利的长期后果有关（例如认知能力下降）。研究这些研究 关联仅限于在寿命的单个点上的横断面研究，而无需考虑 可能影响这些关联的因素。 MTBI/RHI历史悠久与脑血流有关 （CBF）和白质（WM）异常，即使在年轻运动员中也是如此。 CBF和WM异常是两个 一般人群病理衰老和纵向下降的指标。年龄和心血管风险 整个生命周期的因素会影响这些异常。该提议的科学目标是 确定MTBI/RHI对跨病理老化和神经行为功能的MRI指标的影响 寿命。我们的中心假设是MTBI/RHI将与神经行为功能和 CBF/WM异常，并且该关联的强度受年龄增长的独立影响 以及存在心血管危险因素。该项目的理由是确定影响 MTBI/RHI在整个生命周期中的病理老化和神经行为功能的MRI指标以及 影响这种关系的因素将洞悉累积头部损伤的过程 和神经系统衰落后来的生活。我们的假设将以两个特定和一个探索目的进行检验： 1）确定MTBI/RHI与整个生命周期和神经行为功能之间的关联 合并症心血管危险因素的影响； 2）确定MTBI/RHI和MRI之间的关联 整个寿命的病理老化指标以及合并心血管危险因素的影响； 探索性）检查病理衰老的MRI指标是否介导累积之间的关联 MTBI/RHI和整个寿命的神经行为功能。建立独立研究计划 确定MTBI/RHI可以导致长期神经系统疾病负担的机制， 该建议的培训目标是在A）分析和解释中接受专家培训/指导 神经影像学数据，b）衰老和心血管危险因素对长期大脑健康的累积影响 和功能，以及c）由于 mtbi/rhi。我们将通过利用四个大规模的数据来采用创新的寿命方法 在数十年的生活中，对运动员的前瞻性，多中心研究。几位导师的协调 针对运动员的大规模多站点数据集将允许混合前瞻性，横断面设计。我们 将利用先进的分析方法来检查衰老和合并的潜在影响 MTBI/RHI与病理衰老和MRI指标之间关联的心血管危险因素 长期神经行为变化。这项工作很重要，因为它将告知方法以识别 下降的风险，改善长期结局的风险估计，并为干预措施提供治疗目标。

项目成果

Functional Recovery, Symptoms, and Quality of Life 1 to 5 Years After Traumatic Brain Injury.

• DOI: 10.1001/jamanetworkopen.2023.3660
• 发表时间: 2023-03-01
• 期刊: JAMA NETWORK OPEN
• 影响因子: 13.8
• 作者: Nelson, Lindsay D.;Temkin, Nancy R.;Barber, Jason;Brett, Benjamin L.;Okonkwo, David O.;McCrea, Michael A.;Giacino, Joseph T.;Bodien, Yelena G.;Robertson, Claudia;Corrigan, John D.;Diaz-Arrastia, Ramon;Markowitz, Amy J.;Manley, Geoffrey T.
• 通讯作者: Manley, Geoffrey T.

Long-term Multidomain Patterns of Change After Traumatic Brain Injury: A TRACK-TBI LONG Study.

创伤性脑损伤后的长期多域变化模式：一项 TRACK-TBI 长期研究。

• DOI: 10.1212/wnl.0000000000207501
• 发表时间: 2023
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Brett,BenjaminL;Temkin,Nancy;Barber,JasonK;Okonkwo,DavidO;Stein,Murray;Bodien,YelenaG;Corrigan,John;Diaz-Arrastia,Ramon;Giacino,JosephT;McCrea,MichaelA;Manley,GeoffreyT;Nelson,LindsayD;forTRACK-TBIInvestigators
• 通讯作者: forTRACK-TBIInvestigators

A dominance analysis of subjective cognitive complaint comorbidities in former professional football players with and without mild cognitive impairment.

• DOI: 10.1017/s135561772200056x
• 发表时间: 2023-07
• 期刊: JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
• 影响因子: 2.6
• 作者: Brett, Benjamin L.;Kerr, Zachary Yukio;Chandran, Avinash;Walton, Samuel;Aggarwal, Neelum T.;Gifford, Katherine;Mannix, Rebekah;DeFreese, J. D.;Echemendia, Ruben J.;Guskiewicz, Kevin M.;Meehan, William P.;McCrea, Michael A.
• 通讯作者: McCrea, Michael A.

Associations of lifetime concussion history and repetitive head impact exposure with resting-state functional connectivity in former collegiate American football players: An NCAA 15-year follow-up study.

• DOI: 10.1371/journal.pone.0273918
• 发表时间: 2022
• 期刊: PloS one
• 影响因子: 3.7

Longitudinal alterations in cerebral perfusion following a season of adolescent contact sport participation compared to non-contact athletes.

• DOI: 10.1016/j.nicl.2023.103538
• 发表时间: 2023
• 期刊: NEUROIMAGE-CLINICAL
• 影响因子: 4.2
• 作者: Brett, Benjamin L.;Cohen, Alex D.;McCrea, Michael A.;Wang, Yang
• 通讯作者: Wang, Yang