Converging evidence indicates that the presence of midlife vascular risk factors (e.g. hypertension and diabetes) accelerates brain aging and increases the risk of dementia in late life. Conversely, midlife physical activity is associated with the reduced risk of dementia in late life. The potential benefits of regular aerobic exercise on neurocognitive function have been demonstrated in older adults; however, no interventional study has investigated such effects in middle-aged adults. Therefore, the overarching goal of this project is to determine the effects of regular aerobic exercise on neurocognitive function (primary outcome) as well as brain neuronal plasticity and cerebrovascular function (secondary outcomes) in middle-aged adults with subclinical cardiovascular risk factors (i.e. prehypertension and prediabetes). We will address the following aims.
Aim 1 : Determine the effect of regular aerobic exercise on neurocognitive function. Hypothesis: Regular aerobic exercise improves fluid cognitive performance.
Aim 2 : Determine the effect of regular aerobic exercise on brain plasticity. Hypothesis: Regular aerobic exercise increases prefrontal and hippocampal volumes, white matter fiber integrity in the anterior corpus callosum, and functional connectivity of the default-mode-network.
Aim 3 : Determine the impact of regular aerobic exercise on brain perfusion and its relation to neurocognitive function and brain plasticity. Hypotheses: 1) Regular aerobic exercise increases regional brain perfusion while attenuating cerebral blood flow (CBF) pulsatility in the large cerebral arteries; 2) The exercise-related changes in brain perfusion and CBF pulsatility mediate changes in neurocognitive function and brain plasticity. To address our aims, we will conduct 1) a cross-sectional study which compares endurance-trained adults with sedentary subjects with subclinical cardiovascular risk factors and 2) an interventional study in which those sedentary subjects undergo a 1-year program of aerobic exercise training or stretching. Cognitive function will be assessed using the NIH Toolbox Cognitive Battery complemented with sensitive neuropsychological testing on attention-executive function, episodic and working memory, and processing speed. Neuroimaging biomarkers of brain structure and function will be acquired by MRI. Brain perfusion and CBF pulsatility will be measured by arterial spin labeling, 2D time-resolved phase- contrast MRI, and transcranial Doppler. Successful accomplishment of this project will provide the urgently needed knowledge whether regular aerobic exercise improves neurocognitive function in middle-aged individuals who have high risks of developing cognitive decline and dementia in late life.

Public Health Relevance

The U.S. middle-aged adults spend ~55% of their daily life in sedentary behaviors which contribute to the development of vascular risk factors, accelerate cognitive aging, and increase the risk of dementia in late life. The goal of this project is to determine the effects of aerobic exercise training on neurocognitive function, neuroimaging biomarkers of brain plasticity, and cerebrovascular function in middle-aged adults with subclinical cardiovascular risk factors. Understanding the vascular mechanism(s) of neuronal plasticity in response to exercise training provides important mechanistic insights for the development of therapeutic strategies to slow age-related cognitive decline and prevent dementia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Career Transition Award (K99)
Project #
1K99HL133449-01
Application #
9163902
Study Section
NHLBI Mentored Transition to Independence Review Committee (MTI)
Program Officer
Carlson, Drew E
Project Start
2016-08-15
Project End
2018-07-31
Budget Start
2016-08-15
Budget End
2017-07-31
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Ding, Kan; Tarumi, Takashi; Zhu, David C et al. (2018) Cardiorespiratory Fitness and White Matter Neuronal Fiber Integrity in Mild Cognitive Impairment. J Alzheimers Dis 61:729-739
Tarumi, Takashi; Zhang, Rong (2018) Cerebral blood flow in normal aging adults: cardiovascular determinants, clinical implications, and aerobic fitness. J Neurochem 144:595-608
Xing, Chang-Yang; Tarumi, Takashi; Meijers, Rutger L et al. (2017) Arterial Pressure, Heart Rate, and Cerebral Hemodynamics Across the Adult Life Span. Hypertension 69:712-720