Document Type

Thesis

Date of Degree

Spring 2015

Degree Name

MS (Master of Science)

Degree In

Integrative Physiology

First Advisor

Gary L. Pierce

Abstract

Older age is a primary risk factor for the development of cardiovascular disease in part through the stiffening of the large cardiothoracic elastic arteries (e.g., aorta, carotid arteries). Aging is also associated with reduced cognitive function, cerebrovascular reactivity and brain white matter integrity, but whether these changes in brain structure and function are associated with age-related large artery stiffness remains unclear. In contrast, older adults who have high aerobic fitness demonstrate attenuated large artery stiffness and better cognitive performance compared to their sedentary counterparts, but the effects of aerobic fitness on white matter integrity and cerebrovascular reactivity with aging are conflicting and limited. Moreover, whether high aerobic fitness-associated lower large artery stiffness in older adults is associated with, and perhaps mediates, the beneficial changes in cognitive function and white matter structure remains unknown. The purpose of this study was to investigate the extent to which high aerobic fitness is associated with preserved white matter structure, cerebrovascular reactivity, and cognitive performance in aged individuals, and if these changes in brain structure and function are associated with attenuated large artery stiffness. In young (n=19, 23.6 ± 2.5 years) and old (n=22, 64.4 ± 4.2 years) healthy adults, large elastic artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV, aortic stiffness) via non-invasive applanation tonometry of carotid and femoral pulse waveforms and carotid artery beta-stiffness index (β-stiffness index) and compliance using high-resolution ultrasound and carotid blood pressure via applanation tonometry. Aerobic fitness was measured as maximal exercise oxygen uptake (VO2max) using respiratory gas analysis on an upright cycle ergometer. Older subjects were stratified as high or low fit based on gender and age VO2max classification. Letter, pattern and N-Back cognitive tests were used to assess processing speed and working memory respectively. Fractional anisotropy (FA) from diffusion tensor images and Blood Oxygenation Level Dependent (BOLD) imaging was used to assess cerebrovascular reactivity (CVR) response to a breath hold and brain activation during a working memory task. The association between large artery stiffness and FA was then assessed using a voxel-wise general linear model approach and a region-of-interest analysis.

Our results confirmed age-related increases in cfPWV, carotid β-stiffness index and central (carotid) but not brachial systolic blood pressure, and expected reductions in carotid compliance, VO2max, working memory and processing speed, and in white matter integrity in select brain regions (bilateral cingulate, frontal, occipital, temporal). In contrast, we found no age-associated differences in CVR to breath hold stimulus or change in BOLD response to the N-Back. In our cohort of health adults, we found that the age-related changes in large artery stiffness were not attenuated by high compared with low VO2max. Among older adults, large elastic artery stiffness was not associated with regional white matter integrity or cerebrovascular reactivity in any regions-of-interest. Greater carotid artery compliance and lower β-stiffness index was associated with higher processing speed, while compliance was related to higher d'Prime scores and lower reaction time on the 2-Back task among the older adults. CVR to a breath hold stimulus was not related to any measure of cognitive performance. VO2max was not associated with any measures of vascular function, brain structure, function or cognition, indicating relations between large artery stiffness and cognition were independent of aerobic fitness capacity. Taken together, these data suggest that select measures of cognitive performance, but not white matter structure or CVR, may be susceptible to age-related changes in carotid stiffness/compliance and that are unaffected by aerobic fitness. More work is needed to understand the mechanisms by which age-related declines in carotid artery compliance and increased carotid stiffness are associated with reductions in cognitive function in older adults.

Public Abstract

Currently, the aging population continues to grow, increasing healthcare costs associated with cardiovascular disease and dementia. It has been demonstrated that chronic aerobic exercise training is beneficial in slowing the adverse effects of aging on the vasculature, however the relationship between vascular health, the brain and aerobic exercise is not well understood. The goal of this project is to investigate the relationship between age-related declines in the carotid and aortic arteries supplying the brain with blood and brain aging. Additionally, this study aims to examine the role of aerobic exercise in preventing declines in brain health associated with age by preserved arterial health.

In 19 young (n=19, age=23.6 ± 2.5 years) and 22 healthy, older (n= 64.4 ± 4.2 years) adults, arterial stiffness was not associated with brain white matter structure or reactivity to functional stimulus. Greater carotid artery compliance, or the ability of the vessel to distend with increased pressure, was related to better performance on measures of working memory and processing speed in older adults, however this relationship was independent of aerobic fitness capacity. Taken together, these data indicate that the greater compliance of the carotid artery that supplies blood flow to the brain may be associated with better cognitive performance, independent of brain structure and reactivity, in older adults, however, aerobic fitness did not mitigate this relation in our cohort. More work is needed to explore mechanisms by which arterial compliance is related to cognitive performance in older adults.

Keywords

publicabstract, Carotid Compliance, Cerebrovascular Reactivity, Cognition, Vascular Aging, White Matter Integrity

Pages

ix, 57 pages

Bibliography

Includes bibliographical references (pages 53-57).

Copyright

Copyright 2015 Lyndsey DuBose

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