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

基本信息

  • 批准号:
    10651801
  • 负责人:
  • 金额:
    $ 13.22万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 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

项目摘要

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) 在参加运动期间遭受轻度创伤性脑损伤 (mTBI) 和重复性头部撞击 (RHI) 已导致 与不良的长期后果(例如认知能力下降)有关。研究调查这些 关联仅限于生命周期单个点的横断面研究,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,即使在年轻运动员中也是如此。 CBF 和 WM 异常是两种 一般人群病理性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都会影响这些异常。该提案的科学目标是 确定 mTBI/RHI 对病理性衰老和神经行为功能的 MRI 指标的影响 寿命。我们的中心假设是 mTBI/RHI 将与神经行为功能相关 CBF/WM 异常,并且这种关联的强度独立地受到年龄增长的影响 以及心血管危险因素的存在。该项目的基本原理是确定影响 mTBI/RHI 对病理性衰老和整个生命周期神经行为功能的 MRI 指标的影响,以及 影响这种关系的因素将有助于深入了解累积性头部损伤的潜在过程 以及晚年神经功能衰退。我们的假设将通过两个具体目标和一个探索性目标进行检验: 1) 确定 mTBI/RHI 与整个生命周期和神经行为功能之间的关联 合并心血管危险因素的影响; 2) 确定 mTBI/RHI 和 MRI 之间的关联 整个生命周期的病理性衰老指标以及合并心血管危险因素的影响; 探索性)检查病理性衰老的 MRI 指标是否介导累积累积之间的关联 mTBI/RHI 和整个生命周期的神经行为功能。建立独立的研究计划 确定了 mTBI/RHI 可能导致长期神经系统疾病负担的机制, 本提案的培训目标是接受以下方面的专家培训/指导:a) 分析和解释 神经影像数据,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)神经病理学的分子机制和进展 mTBI/RHI。我们将利用来自四个大型、 对运动员数十年生命的前瞻性、多中心研究。多位导师的协调 定向的、大规模的多地点运动员数据集将允许混合前瞻性、横截面设计。我们 将利用先进的分析方法来检查衰老和共病的潜在影响 心血管危险因素对 mTBI/RHI 与病理性衰老 MRI 指标之间关系的影响 长期的神经行为变化。这项工作意义重大,因为它将为识别那些在 下降的风险,改善长期结果的风险估计,并为干预的治疗目标提供信息。

项目成果

期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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:
  • 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:
  • 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:
  • 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.
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:
  • 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
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Benjamin L Brett其他文献

Benjamin L Brett的其他文献

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{{ truncateString('Benjamin L Brett', 18)}}的其他基金

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:
    10282566
  • 财政年份:
    2021
  • 资助金额:
    $ 13.22万
  • 项目类别:
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:
    10455046
  • 财政年份:
    2021
  • 资助金额:
    $ 13.22万
  • 项目类别:

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