Impact of Combat Exposure on Structural and Functional Brain Connectivity and Risk forAlzheimer's Disease in Aging Veterans
战斗暴露对老年退伍军人大脑结构和功能连接以及阿尔茨海默病风险的影响
基本信息
- 批准号:10364388
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAmygdaloid structureAmyloidBehavioralBiologicalBiological MarkersBody mass indexBostonBrainBrain imagingCaringCenter for Translational Science ActivitiesCognition DisordersCognitiveCohort StudiesDataDementiaDeteriorationDiabetes MellitusDiseaseElderlyEquipment and supply inventoriesExposure toFundingGenerationsHealthHealth Care CostsHealthcare SystemsHypertensionImpaired cognitionImpairmentLeadLife StyleLinkMapsMeasuresMediator of activation proteinMedicalMemoryMilitary PersonnelModelingNerve DegenerationParticipantPathologyPathway AnalysisPhysiologicalPost-Traumatic Stress DisordersPrevalencePreventive measurePrincipal InvestigatorProceduresProxyRestRiskRisk FactorsSamplingStatistical ModelsStressStructureSymptomsSystemTestingTraumaVeteransVisitWaxesWorkagedassociated symptomcognitive developmentcognitive functioncognitive performancecognitive reservecohortcombatdisorder riskemerging adultfollow-upfunctional independencehypercholesterolemiainsightmild traumatic brain injurymilitary servicemilitary traumamilitary veteranmultimodalitynervous system disorderneural circuitneuroimagingneuromechanismnon-dementedrelating to nervous systemresilienceserial imagingsocietal costsstress disordersupport networktau Proteinstrendwhite matteryoung adult
项目摘要
Military service in young adulthood is typically accompanied by a variety of combat exposures
that are known to increase the risk for cognitive impairment and Alzheimer’s disease (AD) in
later life (e.g. hypertension, diabetes, hypercholesterolemia, and body mass index). Although
the significant healthcare and societal costs of combat exposure are well documented, it is
possible that these primary young adulthood exposures additionally promote later life secondary
conditions that are only now being uncovered. Identification of factors that contribute to
advanced risk for diseases of aging in older Veterans provides the opportunity to test and
initiate treatments that may slow progression of these conditions. Additionally, these data could
be used to inform care for the younger, current generation of veterans, including the initiation of
lifestyle and medical changes that may ameliorate progression of conditions that promote later
life cognitive and behavioral conditions. It is possible that combat-exposure in young adulthood
initiates a trajectory of ‘unhealthy aging’ with progressive elevation in biological risk that
promotes aging-related neural ‘disconnection’ of structural and functional brain networks.
However, limited work to date has been performed linking young adulthood combat exposure to
alterations in neural structure and function in older Veterans. Additionally, whether combat-
exposure in young adulthood is related to the accumulation of late life biomarker hallmarks of
AD, known as the amyloid, tau, neurodegeneration (A-T-N) framework, is currently unknown.
Thus, intermediary mechanisms linking young adulthood combat exposure to late life risk must
be examined. In the large Translational Research Center for TBI and Stress Disorders
(TRACTS) cohort study, we find that younger Veterans with combat exposures and symptoms
additionally 1) have elevations in systemic biological risk; 2) show alterations in critical brain
network circuitry such as amygdala and default mode network (DMN); and 3) show accelerated
aging trends in structural connectivity and white matter microstructure. We aim to conceptually
link these findings in the proposed work. We propose that late life risk is conferred first through
elevation in systemic health conditions starting in young adulthood (i.e. ‘cumulative biological
risk’) that lead to damage to critical brain connections. Combined effects of cumulative biological
risk accelerate the deterioration of structural and functional brain networks that support higher
cognitive function, including memory systems and/or compensatory systems that provide
cognitive reserve in the face of AD pathology. We will test a model of combat-associated
amygdala network dysregulation promoting systemic health risk in young adulthood. This
cumulative biological risk in turn contributes to neural and cognitive deterioration that is
pronounced in older Veterans. This work will elucidate mechanisms that contribute to elevated
risk for cognitive impairment in combat exposed military Veterans and can be used to inform
treatments in older Veterans but also may inform preventative measures for young Veterans at
risk for later life neurological disorders.
青年时期的兵役通常伴随着各种各样的战斗暴露
已知会增加认知障碍和阿尔茨海默病(AD)的风险,
晚年生活(如高血压、糖尿病、高胆固醇血症和体重指数)。虽然
战斗暴露的重大医疗保健和社会成本是有据可查的,
这些初级的年轻成年期暴露可能还促进了后来的生活次级
这些情况现在才被发现。查明造成
老年退伍军人中老年疾病的高级风险提供了测试和
启动可能减缓这些疾病进展的治疗。此外,这些数据可以
被用来通知照顾年轻的,当代退伍军人,包括启动
生活方式和医疗变化,可能会改善病情的进展,促进以后
生活认知和行为状况。有可能在年轻的成年期,
启动了“不健康老龄化”的轨迹,生物风险逐渐升高,
促进结构和功能大脑网络的老化相关神经“断开”。
然而,到目前为止,有限的工作已经完成,将年轻的成年人战斗暴露与
老年退伍军人神经结构和功能的改变。此外,无论战斗-
在年轻的成年期暴露与晚期生命生物标志物的积累有关,
AD,被称为淀粉样蛋白,tau,神经变性(A-T-N)框架,目前尚不清楚。
因此,将青年期与晚年风险联系起来的中介机制必须
接受检查。在大型创伤性脑损伤和应激障碍转化研究中心,
(TRACTS)队列研究,我们发现,年轻的退伍军人与战斗暴露和症状,
此外,1)全身生物学风险升高; 2)关键脑功能改变
网络电路,如杏仁核和默认模式网络(DMN);和3)显示加速
结构连通性和白色物质微观结构的老化趋势。我们的目标是在概念上
将这些发现与拟议的工作联系起来。我们建议,晚期生命风险首先通过
从青年期开始的全身健康状况的升高(即“累积生物学效应”)
风险”),导致关键大脑连接受损。累积生物学效应的综合效应
风险加速了大脑结构和功能网络的恶化,
认知功能,包括记忆系统和/或补偿系统,
认知储备在面对AD病理。我们将测试一种与战斗有关的模型,
杏仁核网络失调促进青年期全身健康风险这
累积的生物风险反过来又会导致神经和认知功能的退化,
在老年退伍军人中,这项工作将阐明机制,有助于提高
暴露于战斗的退伍军人中认知障碍的风险,并可用于告知
老年退伍军人的治疗,但也可能告知年轻退伍军人的预防措施,
晚年神经系统疾病的风险。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
DAVID H SALAT其他文献
DAVID H SALAT的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('DAVID H SALAT', 18)}}的其他基金
Impact of Combat Exposure on Structural and Functional Brain Connectivity and Risk forAlzheimer's Disease in Aging Veterans
战斗暴露对老年退伍军人大脑结构和功能连接以及阿尔茨海默病风险的影响
- 批准号:
10591407 - 财政年份:2022
- 资助金额:
-- - 项目类别:
NEURAL PHENOTYPES OF RESISTANCE AND RESILIENCY TO AD AND ADRD IN THE OLDEST OF THE OLD
最古老的老年人对 AD 和 ADRD 的抵抗和恢复的神经表型
- 批准号:
10283071 - 财政年份:2021
- 资助金额:
-- - 项目类别:
NEURAL PHENOTYPES OF RESISTANCE AND RESILIENCY TO AD AND ADRD IN THE OLDEST OF THE OLD
最古老的老年人对 AD 和 ADRD 的抵抗和恢复的神经表型
- 批准号:
10673910 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Decoupling neural and vascular functional pathology in individuals at risk for Alzheimer's disease- U.S.-Japan Brain Research Cooperative Program (BRCP) Administrative Supplement
解耦阿尔茨海默病风险个体的神经和血管功能病理学 - 美日脑研究合作计划 (BRCP) 行政补充文件
- 批准号:
10020696 - 财政年份:2020
- 资助金额:
-- - 项目类别:
MAPPING THE HUMAN CONNECTOME DURING TYPICAL AGING
绘制典型衰老过程中的人类连接组图
- 批准号:
10160408 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Cerebrovascular Contributions to Brain Aging and Dementia
脑血管对大脑衰老和痴呆的影响
- 批准号:
8071338 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Cerebrovascular Contributions to Brain Aging and Dementia
脑血管对大脑衰老和痴呆的影响
- 批准号:
7860530 - 财政年份:2007
- 资助金额:
-- - 项目类别:
Cerebrovascular Contributions to Brain Aging and Dementia
脑血管对大脑衰老和痴呆的影响
- 批准号:
7503987 - 财政年份:2007
- 资助金额:
-- - 项目类别:
Cerebrovascular Contributions to Brain Aging and Dementia
脑血管对大脑衰老和痴呆的影响
- 批准号:
7262316 - 财政年份:2007
- 资助金额:
-- - 项目类别:
Cerebrovascular Contributions to Brain Aging and Dementia
脑血管对大脑衰老和痴呆的影响
- 批准号:
8514341 - 财政年份:2007
- 资助金额:
-- - 项目类别:
相似海外基金
Interplay between Aging and Tubulin Posttranslational Modifications
衰老与微管蛋白翻译后修饰之间的相互作用
- 批准号:
24K18114 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Early-Career Scientists
EMNANDI: Advanced Characterisation and Aging of Compostable Bioplastics for Automotive Applications
EMNANDI:汽车应用可堆肥生物塑料的高级表征和老化
- 批准号:
10089306 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Collaborative R&D
The Canadian Brain Health and Cognitive Impairment in Aging Knowledge Mobilization Hub: Sharing Stories of Research
加拿大大脑健康和老龄化认知障碍知识动员中心:分享研究故事
- 批准号:
498288 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Operating Grants
Baycrest Academy for Research and Education Summer Program in Aging (SPA): Strengthening research competencies, cultivating empathy, building interprofessional networks and skills, and fostering innovation among the next generation of healthcare workers t
Baycrest Academy for Research and Education Summer Program in Aging (SPA):加强研究能力,培养同理心,建立跨专业网络和技能,并促进下一代医疗保健工作者的创新
- 批准号:
498310 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Operating Grants
関節リウマチ患者のSuccessful Agingに向けたフレイル予防対策の構築
类风湿性关节炎患者成功老龄化的衰弱预防措施的建立
- 批准号:
23K20339 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (B)
Life course pathways in healthy aging and wellbeing
健康老龄化和福祉的生命历程路径
- 批准号:
2740736 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Studentship
NSF PRFB FY 2023: Connecting physiological and cellular aging to individual quality in a long-lived free-living mammal.
NSF PRFB 2023 财年:将生理和细胞衰老与长寿自由生活哺乳动物的个体质量联系起来。
- 批准号:
2305890 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Fellowship Award
I-Corps: Aging in Place with Artificial Intelligence-Powered Augmented Reality
I-Corps:利用人工智能驱动的增强现实实现原地老龄化
- 批准号:
2406592 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
McGill-MOBILHUB: Mobilization Hub for Knowledge, Education, and Artificial Intelligence/Deep Learning on Brain Health and Cognitive Impairment in Aging.
McGill-MOBILHUB:脑健康和衰老认知障碍的知识、教育和人工智能/深度学习动员中心。
- 批准号:
498278 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Operating Grants
Welfare Enhancing Fiscal and Monetary Policies for Aging Societies
促进老龄化社会福利的财政和货币政策
- 批准号:
24K04938 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)