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Title:Understanding the role of cerebrovascular health in cognitive aging: a multi-modal noninvasive human neuroimaging approach
Author(s):Zimmerman, Benjamin Joseph
Director of Research:Gratton, Gabriele; Fabiani, Monica
Doctoral Committee Chair(s):Gratton, Gabriele; Fabiani, Monica
Doctoral Committee Member(s):Sutton, Bradley P; Barbey, Aron K
Department / Program:Neuroscience
Discipline:Neuroscience
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):cognitive aging
cerebral blood flow
cardiorespiratory fitness
arterial spin labelling
near-infrared spectroscopy
arterial compliance
Abstract:The brain’s vasculature undergoes age-related physiological and anatomical changes similarly to the rest of the cardiovascular system. However, the health of the cerebrovasculature may be related to cognitive ability. Thus, it is critical to determine the effect of cerebrovascular health on cognition and the mediators of cerebrovascular health across the lifespan. Since aerobic fitness is known to alleviate both cognitive and volumetric losses in the brain, it is important to investigate some of the possible mechanisms underlying these beneficial changes. In one experiment, we investigated the role that cardiorespiratory fitness (CRF) plays in determining the relationship between aging and cerebral blood flow (CBF) in a group of older adults (ages 55-85). Using arterial spin labeling (ASL) to quantify CBF, we found that blood flow in the gray matter was positively correlated with CRF and negatively correlated with age (Zimmerman et al., 2014). Subsequent analyses revealed that CRF fully mediated the effects of age on CBF in the gray matter, but not in the white matter. Whether this same effect holds true for younger adults is unknown. In the next study, using a large sample of resting cerebral blood flow measured with arterial spin labelling in younger adults, we demonstrate that the relationship between cardiorespiratory fitness and cerebral blood flow is negative. Although the relationship is weak, the observation demonstrates that the interpretation of resting cerebral blood flow as a measure of cerebrovascular health should be made with caution. In order to gain an improved understanding of how cerebrovascular health impacts cognitive aging and relates to CRF, ASL was used in a third study to investigate both the resting and activation CBF in healthy older adults ranging in age from 56-88. To this end, we analyzed measures of both baseline CBF and changes in CBF during activation from a visual task. We found that the change in CBF in the visual cortex to a reversing checkerboard stimulus, but not the baseline CBF, was associated with neuropsychological measures of executive function. While baseline CBF was correlated with age and CRF, the change in CBF was correlated with the participants’ pulse pressure. These results indicate that the measures of baseline CBF and activation-related CBF are separable measures of vascular health in older age that relate differentially to measures of physiology and cognition. Because reactivity measures are dynamic and contain a temporal component, we were interested in whether improved temporal resolution could reveal differences in the time course of cerebrovascular reactivity across age or arterial compliance. In this final study, multi-distance, frequency-domain near infrared spectroscopy (NIRS) was used to measure changes in oxy- and deoxy-hemoglobin concentrations induced by breath holding in the right prefrontal cortex concurrently with ASL in a magnetic resonance imaging (MRI) scanner. Studying participants ranging in age from 55-87, we found that the superior temporal resolution of NIRS allowed us to observe differences in the speed of the oxy-hemoglobin response to a period of breath holding between our older and younger participants and between participants split by arterial compliance, where older individuals and participants with stiffer arteries tended to have a delayed hemodynamic response. This finding highlights the usefulness of utilizing a multi-modal neuroimaging approach for the investigation of time-sensitive aspects of cerebrovascular health. Overall, this set of experiments highlights the complexity of measures of cerebrovascular health both across the lifespan and in their relationships to cognition. We demonstrated that in older adults, resting CBF was related to CRF, and CRF mediated age-related declines in CBF. Interestingly, the relationship between CBF and CRF reversed in a sample of younger adults. Further analysis revealed that resting CBF did not predict cognitive decline in a sample of older adults. In contrast, the level of task-related change in CBF did positively relate to executive functioning. Pursuing measures of reactivity further, we found that adding NIRS measures provided temporal resolution that allowed us to see differences in the timing of cerebrovascular reactivity across age and arterial compliance in the brain. These timing differences may be complementary to the amplitude differences found through ASL, and future research will continue to resolve these separable components of cerebrovascular health.
Issue Date:2016-09-30
Type:Thesis
URI:http://hdl.handle.net/2142/95550
Rights Information:Copyright 2016 Benjamin Zimmerman
Date Available in IDEALS:2017-03-01
Date Deposited:2016-12


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