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) 在参加运动期间暴露于轻度创伤性脑损伤(MTBI)和重复头部撞击(RHI)有 与不良的长期后果有关(例如，认知能力下降)。调查这些问题的研究 相关研究仅限于在寿命的单个时间点进行横断面研究，而没有考虑 可以影响这些关联的因素。较大的mTBI/RHI病史与脑血流量相关 (CBF)和白质(WM)异常，即使在较年轻的运动员中也是如此。CBF和WM异常是两种 一般人口病理性老龄化和纵向衰退的指标。年龄与心血管风险 生命周期中的各种因素都会影响这些异常。这项提议的科学目标是 确定mTBI/RHI对病理性衰老和神经行为功能的MRI指标的影响 生命的长短。我们的中心假设是mTBI/RHI将与神经行为功能和 CBF/WM异常，这种联系的强度独立地受到年龄的增加的影响 以及心血管危险因素的存在。这个项目的基本原理是确定影响 MTBI/RHI对病理性衰老和一生中神经行为功能的MRI指标的影响 影响这种关系的因素，将提供对累积性头部损伤潜在过程的洞察 以及晚年的神经功能衰退。我们的假设将通过两个具体的和一个探索性的目标进行检验： 1)确定mTBI/RHI与神经行为功能之间的关系 合并心血管危险因素的影响2)确定mTBI/RHI与MRI的相关性 整个生命周期的病理性衰老指标以及共患心血管危险因素的影响； 探索性)检查病理性衰老的MRI指标是否调解累积衰老之间的关联 MTBI/RHI和整个寿命的神经行为功能。建立独立的研究计划 确定了mTBI/RHI可导致长期神经疾病负担的机制， 本提案的培训目标是接受a)分析和解释方面的专家培训/指导 神经成像数据，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)神经病理的分子机制和进展 MTBI/RHI。我们将采用创新的生命周期方法，利用来自四个大型、 对运动员几十年的前瞻性、多中心研究。协调几位导师- 定向的、大规模的运动员多站点数据集将允许进行混合的前瞻性、横断面设计。我们 将利用先进的分析方法来检查老龄化和共病的潜在影响 MTBI/RHI与病理性衰老MRI指标相关性的心血管危险因素 长期的神经行为改变。这项工作具有重要意义，因为它将为识别那些在 降低风险，改善对长期结果的风险估计，并为干预提供治疗目标。

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.

前大学足球运动员的终生脑震荡历史和重复的头部影响与静止状态功能连通性的关联：NCAA 15年的随访研究。

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

Subjective and Performance-Based Cognition and Their Associations with Head Injury History in Older Former National Football League Players.

主观和基于表现的认知及其与老年前国家橄榄球联盟球员头部受伤史的关联。

• DOI: 10.1249/mss.0000000000003256
• 发表时间: 2023
• 期刊: Medicine and science in sports and exercise
• 影响因子: 4.1
• 作者: Allen,AndrewT;Cole,WesleyR;Walton,SamuelR;Kerr,ZacharyYukio;Chandran,Avinash;Mannix,Rebekah;Guskiewicz,KevinM;Meehan3rd,WilliamP;Echemendia,RubenJ;McCrea,MichaelA;Brett,BenjaminL
• 通讯作者: Brett,BenjaminL