Arterial Aging, Brain Perfusion & Exercise: Impact on Brain Structure & Function.

动脉老化、脑灌注

• 批准号: 8452128
• 负责人: RONG ZHANG
• 金额: $ 49.52万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8452128
• 关键词: Address; Aerobic Exercise; Age; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease risk; American; Anterior; Attenuated; Balance training; Biological Markers; Blood Flow Velocity; Blood Vessels; Blood specimen; Brain; Brain imaging; Brain region; Brain-Derived Neurotrophic Factor; C-reactive protein; Carbon Dioxide; Cardiovascular system; Centers for Disease Control and Prevention (U.S.); Cerebral Atheroscleroses; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Chronic; Cognition; Cognitive; Control Groups; Cross-Sectional Studies; Dementia; Diabetes Mellitus; Dyslipidemias; Elderly; Environmental Risk Factor; Exercise; Exhibits; Experimental Designs; Functional disorder; General Population; Genetic; Goals; Health; Hippocampus (Brain); Homeostasis; Human; Hypertension; Imaging technology; Impaired cognition; Individual; Inflammation; Insulin-Like Growth Factor I; Interleukin-6; Intervention; Knowledge; Lead; Learning; Lesion; Life; Linear Models; Link; Longevity; Longitudinal Studies; Magnetic Resonance Imaging; Maps; Measurement; Measures; Medial; Mediating; Mediation; Memory; Metabolic; Microcirculation; Modeling; Monitor; Nature; Neurocognitive; Neuropsychological Tests; Observational Study; Pattern; Perfusion; Perfusion Weighted MRI; Physical activity; Physiological; Prevalence; Preventive; Preventive Intervention; Public Health; Pulse Pressure; Randomized; Randomized Controlled Trials; Research; Resistance; Resolution; Risk Factors; Rodent; Role; Science; Statistical Methods; Structure; Temporal Lobe; Testing; Training; Training Programs; Ultrasonography; Uncertainty; Vasodilation; Vasomotor; Work; age related cognitive disorder; aged; aging brain; angiogenesis; arterial stiffness; brain volume; cardiovascular risk factor; cerebral atrophy; cerebrovascular; cognitive function; effective therapy; electric impedance; executive function; flexibility; follow-up; improved; information processing; long term memory; meetings; middle age; middle cerebral artery; neural circuit; neurogenesis; novel; pressure; processing speed; public health relevance; relating to nervous system; response; retiree; scaffold; social; synaptogenesis; theories; tonometry; vasoconstriction; white matter

DESCRIPTION (provided by applicant): Advanced age is a major risk factor for cognitive decline. Accumulating evidence demonstrates the importance of physical activity for preserving brain health in older adults. However, at present, we know very little about the underlying mechanisms. Arterial stiffening and increases in central pulse pressure are the hallmark of arterial aging which may have significant impact on brain perfusion. The overall objective of this proposal is to test the central hypothesis that exercise training improves brain perfusion by modifying arterial aging and these changes lead to increases in regional brain volume and reductions in white matter lesions, and thus improvement in cognitive function in older adults over 65. The following specific aims will be accomplished: 1) to determine whether increases in arterial stiffness and central pulse pressure with age are associated with increases in cerebrovascular resistance/impedance, reduction in brain perfusion and cerebrovascular dysfunction; 2) to determine whether exercise training improves brain perfusion by modifying arterial aging as indicated by reductions in cerebrovascular resistance/impedance, arterial stiffness, central pulse pressure and/or improvement in vascular endothelial function; 3) to determine whether improvement in brain perfusion with exercise training leads to increases in regional brain volume, reductions in white matter lesions and improvement in cognitive function. To accomplish this goal, a cross-sectional study of the young, middle-aged and elderly individuals will be conducted for aim 1. Furthermore, a longitudinal study of aerobic exercise training and control (flexibility and balance training) will be conducted for one year in the elderly for aim 2 and 3. The state-of-the-art transcranial Doppler and magnetic resonance imaging will be used to measure changes in brain perfusion and structure. A comprehensive battery of neuropsychological testing sensitive to age will be used to measure changes in cognitive function. Advanced statistical methods of multiple variable regression and mediation model analysis will be used to determine the relationship between arterial aging, brain perfusion, structure and cognitive function.

描述（由申请人提供）：高龄是认知能力下降的主要风险因素。越来越多的证据表明，身体活动对保持老年人大脑健康的重要性。然而，目前，我们对潜在的机制知之甚少。动脉硬化和中心脉压的增加是动脉老化的标志，这可能对脑灌注有显著影响。本提案的总体目标是检验中心假设，即运动训练通过改变动脉老化改善脑灌注，这些变化导致局部脑容量增加和白色病变减少，从而改善65岁以上老年人的认知功能。将实现以下具体目标：1）确定动脉硬度和中心脉压随年龄的增加是否与脑血管阻力/阻抗增加、脑灌注减少和脑血管功能障碍相关; 2）确定运动训练是否通过改变动脉老化来改善脑灌注，如脑血管阻力/阻抗，动脉硬度，中枢脉压和/或血管内皮功能的改善; 3）确定运动训练对脑灌注的改善是否导致局部脑体积的增加、白色物质病变的减少和认知功能的改善。为了实现这一目标，将针对目标1进行青年、中年和老年人的横断面研究。此外，还将针对目标2和3在老年人中进行为期一年的有氧运动训练和控制（灵活性和平衡训练）的纵向研究。最先进的经颅多普勒和磁共振成像将用于测量脑灌注和结构的变化。一套对年龄敏感的综合神经心理学测试将用于测量认知功能的变化。将使用多元回归和中介模型分析的先进统计方法来确定动脉老化、脑灌注、结构和认知功能之间的关系。

项目成果

Midlife aerobic exercise and brain structural integrity: Associations with age and cardiorespiratory fitness.

• DOI: 10.1016/j.neuroimage.2020.117512
• 发表时间: 2021-01-15
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Tarumi T;Tomoto T;Repshas J;Wang C;Hynan LS;Cullum CM;Zhu DC;Zhang R
• 通讯作者: Zhang R

Cerebral hemodynamics of the aging brain: risk of Alzheimer disease and benefit of aerobic exercise.

• DOI: 10.3389/fphys.2014.00006
• 发表时间: 2014
• 期刊: Frontiers in physiology
• 影响因子: 4
• 作者: Tarumi T;Zhang R
• 通讯作者: Zhang R

Ambulatory pulse pressure, brain neuronal fiber integrity, and cerebral blood flow in older adults.

老年人的动态脉压、脑神经元纤维完整性和脑血流量。

• DOI: 10.1177/0271678x17745027
• 发表时间: 2019
• 期刊: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
• 作者: Tarumi,Takashi;Thomas,BinuP;Wang,Ciwen;Zhang,Li;Liu,Jie;Turner,Marcel;Riley,Jonathan;Tangella,Nikita;Womack,KyleB;Kerwin,DianaR;Cullum,CMunro;Lu,Hanzhang;Vongpatanasin,Wanpen;Zhu,DavidC;Zhang,Rong
• 通讯作者: Zhang,Rong

Hippocampal and rostral anterior cingulate blood flow is associated with affective symptoms in chronic traumatic brain injury.

• DOI: 10.1016/j.brainres.2021.147631
• 发表时间: 2021-11-15
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Thomas BP;Tarumi T;Wang C;Zhu DC;Tomoto T;Munro Cullum C;Dieppa M;Diaz-Arrastia R;Bell K;Madden C;Zhang R;Ding K
• 通讯作者: Ding K

Aerobic exercise training reduces cerebrovascular impedance in older adults: a 1-year randomized controlled trial.

有氧运动训练可降低老年人的脑血管阻抗：一项为期一年的随机对照试验。

• DOI: 10.1152/japplphysiol.00241.2022
• 发表时间: 2022
• 期刊: Journal of applied physiology (Bethesda, Md. : 1985)
• 作者: Sugawara,Jun;Tarumi,Takashi;Xing,Changyang;Liu,Jie;Tomoto,Tsubasa;Pasha,EvanP;Zhang,Rong
• 通讯作者: Zhang,Rong