Lifespan Vascular Biology on White Matter

白质的寿命血管生物学

• 批准号: 10052859
• 负责人: L Elliot Elliot Hong
• 金额: $ 310.87万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2024-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10052859
• 关键词: 3-Dimensional; Adolescence; Age; Age-associated memory impairment; Aging; Alcohol consumption; Alzheimer' s Disease; Alzheimer' s disease risk; Amish; Amyloid beta-Protein; Anatomy; Automobile Driving; Biological Markers; Biology; Blood Vessels; Brain; Brain imaging; Brain region; Cardiovascular system; Cerebrovascular Circulation; Cerebrum; Clinical; Cognition; Cohort Effect; Collaborations; Communities; Coupling; Data; Dementia; Development; Diffusion Magnetic Resonance Imaging; Endothelium; Family; Gap Junctions; Goals; Health; Image; Imaging Techniques; Impaired cognition; Individual; Label; Lesion; Life; Life Style; Longevity; Measures; Mediating; Medicine; Mennonite; Modeling; Multimodal Imaging; Multivariate Analysis; Natural History; Neurologic; Organ; Pathogenesis; Pathway interactions; Patients; Pattern; Perfusion; Physiologic pulse; Policies; Population; Prevention; Prevention program; Process; Productivity; Regional Disease; Research; Risk; Risk Factors; Rural; Scientist; Specificity; Spin Labels; Structure; Testing; Time; Tobacco use; United States National Institutes of Health; Vascular Cognitive Impairment; Vascular Endothelium; Vasodilation; White Matter Hyperintensity; age effect; age related; aging brain; allostatic load; arterial stiffness; cardiometabolic risk; cardiovascular risk factor; cohort; connectome; effective therapy; endothelial dysfunction; follow-up; genetic profiling; imaging modality; indexing; insight; neuroimaging; novel; prevent; reactive hyperemia; white matter; white matter change; young adult

Project Summary / Abstract Vascular biology and white matter may be some of the key junctures that harbor early risk mechanisms that precipitate vascular contributions to cognitive impairment and Alzheimer's disease. This process may start as early as adolescence and young adulthood, and through our lifespan. While cardiovascular impacts on white matter health are well-established, our understanding of the lifetime course and the associated mechanisms are less clear. Our efforts aim to identify the earliest possible vascular biomarkers and risk factors for abnormal white matter changes for the corresponding cognitive declines. Cardiovascular-brain studies typical focus on structural imaging changes that are difficult to reverse. We hypothesize that white matter lifespan changes can be more sensitively tracked by combining standard structural imaging techniques with state-of-the-art connectome era multimodal imaging. The goal is to uncover novel vascular - white matter mechanisms and biomarkers that provide early warnings before the irreversible structural changes occur. The proposal builds upon the productivity of the Amish Connectome Project as baseline data, and leverages the collaboration between our brain imaging and cardiovascular medicine groups. The Old Order Amish/Mennonite population has a more uniform genetic profile, rural lifestyle and low alcohol and tobacco use that greatly reduce uncontrollable variability, thus providing a particularly advantageous platform to study the vascular mechanisms on white matter. Cerebral white matter will also be studied in the context of predicting white matter vulnerability to Alzheimer's disease. Tracking when the aberrant vascular – white matter coupling occurs may provide insights into the timing and mode for more effective prevention. This proposal is responsive to the new NIH Inclusion Across the Lifespan policy. If successful, the proposed study should strongly support the prevention goal highlighted in the National Alzheimer's Project Act, which supports increased public research to prevent the onset of and develop effective treatments for AD by 2025. Prevention programs can be benefited by more nuanced understanding of the pathways connecting early vascular changes to irreversible white matter changes. Therefore, we propose to use cutting-edge white matter imaging that is informative of the underlying mechanisms, combined with standard but state-of-the-art vascular assessments, to study the interaction between vascular and white matter changes across lifespan.

项目总结/摘要 血管生物学和白色物质可能是隐藏早期风险机制的一些关键结合点， 血管对认知障碍和阿尔茨海默病的影响。该过程可以开始为 早在青春期和青年期，并贯穿我们的一生。而心血管疾病对白色 我们对生命历程和相关机制的理解 不太清楚。我们的努力旨在确定最早的可能的血管生物标志物和异常的风险因素。 白色物质的变化对应认知能力的下降。脑血管研究的典型重点是 难以逆转的结构成像变化。我们假设白色物质寿命的变化 通过将标准结构成像技术与最先进的技术相结合， 连接体时代的多模态成像。目的是揭示新的血管-白色物质机制， 生物标志物，在不可逆的结构变化发生之前提供早期预警。该提案建立 将Amish Connectome项目的生产力作为基线数据，并利用 脑成像和心血管医学之间的联系。旧秩序阿米什人/门诺派人口 具有更一致的遗传特征，农村生活方式和低酒精和烟草使用，大大减少了 不可控的变异性，从而提供了一个特别有利的平台来研究血管 白色物质的机制。大脑白色物质也将在预测白色的背景下进行研究。 对阿尔茨海默病的易感性。异常血管-白色物质耦合时的跟踪 发生的时间可以提供更有效预防的时间和模式的见解。这项建议是 响应新的NIH Inclusion Across the Lifespan政策。如果成功，拟议的研究应 强烈支持国家阿尔茨海默病项目法案中强调的预防目标，该法案支持 增加公共研究，以预防AD的发病并在2025年前开发有效的治疗方法。预防 通过对连接早期血管的通路进行更细致的了解， 不可逆的白色物质变化。因此，我们建议使用尖端的白色物质成像 这是潜在机制的信息，结合标准但最先进的血管 评估，以研究整个生命周期中血管和白色物质变化之间的相互作用。

项目成果

Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study.

连接体结构塑造了精神分裂症的大规模皮质改变：一项全球 ENIGMA 研究。

• DOI: 10.1038/s41380-024-02442-7
• 发表时间: 2024
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Georgiadis,Foivos;Larivière,Sara;Glahn,David;Hong,LElliot;Kochunov,Peter;Mowry,Bryan;Loughland,Carmel;Pantelis,Christos;Henskens,FransA;Green,MelissaJ;Cairns,MurrayJ;Michie,PatriciaT;Rasser,PaulE;Catts,Stanley;Tooney,Pau
• 通讯作者: Tooney,Pau

A new Mendelian Randomization method to estimate causal effects of multivariable brain imaging exposures.

一种新的孟德尔随机化方法，用于估计多变量脑成像暴露的因果影响。

• 发表时间: 2022
• 期刊: Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
• 作者: Mo,Chen;Ye,Zhenyao;Ke,Hongjie;Lu,Tong;Canida,Travis;Liu,Song;Wu,Qiong;Zhao,Zhiwei;Ma,Yizhou;Hong,LElliot;Kochunov,Peter;Ma,Tianzhou;Chen,Shuo
• 通讯作者: Chen,Shuo

Behavioral, Anatomical and Heritable Convergence of Affect and Cognition in Superior Frontal Cortex.

• DOI: 10.1016/j.neuroimage.2021.118561
• 发表时间: 2021-11
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Kraljević N;Schaare HL;Eickhoff SB;Kochunov P;Yeo BTT;Kharabian Masouleh S;Valk SL
• 通讯作者: Valk SL

The additive impact of cardio-metabolic disorders and psychiatric illnesses on accelerated brain aging.

• DOI: 10.1002/hbm.25769
• 发表时间: 2022-04-15
• 期刊: Human brain mapping
• 影响因子: 4.8
• 作者: Ryan MC;Hong LE;Hatch KS;Gao S;Chen S;Haerian K;Wang J;Goldwaser EL;Du X;Adhikari BM;Bruce H;Hare S;Kvarta MD;Jahanshad N;Nichols TE;Thompson PM;Kochunov P
• 通讯作者: Kochunov P

Brain deficit patterns of metabolic illnesses overlap with those for major depressive disorder: A new metric of brain metabolic disease.

• DOI: 10.1002/hbm.26235
• 发表时间: 2023-04-15
• 期刊: HUMAN BRAIN MAPPING
• 影响因子: 4.8
• 作者: Hatch, Kathryn S.;Gao, Si;Ma, Yizhou;Russo, Alessandro;Jahanshad, Neda;Thompson, Paul M.;Adhikari, Bhim M.;Bruce, Heather;Van Der Vaart, Andrew;Sotiras, Aristeidis;Kvarta, Mark D.;Nichols, Thomas E.;Schmaal, Lianne;Hong, L. Elliot;Kochunov, Peter
• 通讯作者: Kochunov, Peter