Author ORCID Identifier

https://orcid.org/0009-0000-2915-6584

Date Available

5-20-2026

Year of Publication

2024

Degree Name

Master of Science (MS)

Document Type

Master's Thesis

College

Arts and Sciences

Department/School/Program

Psychology

First Advisor

Dr. Justin E. Karr

Abstract

Older adults experience a chronic state of heightened immune response referred to as “inflammaging” which can be observed by detecting levels of proinflammatory cytokines in blood serum. These proinflammatory cytokines are secreted in the central nervous system and may also enter the brain through the blood brain barrier. Previous literature has suggested that extracellular free water, a magnetic resonance imaging metric, may allow us to detect alterations in the extracellular space which are thought to correlate with inflammation in the central nervous system. This study examined the correlation between two proinflammatory cytokines, IL-6 and TNFα, collected longitudinally and cross-sectionally imaged extracellular free water. There was a positive correlation between extracellular free water and concurrent levels of IL-6 and TNFα (IL- 6 intercept: .455, p < .01; TNFα intercept: r=.240, p < .05). Extracellular free water was also associated with faster decreasing IL-6 and faster increasing TNFα over time (IL-6 slope: r=-.444, p < .01; TNFα slope: r=.297, p < .01). The study also examined the relationship between extracellular free water and performances on neuropsychological tests of executive function and memory and self-reported cognitive function. Extracellular free water did not significantly predict performance on neuropsychological tests of executive function or memory but did significantly predict subjective cognitive functioning above and beyond estimates of TNFα ( =-.26, 95% CI [-.50, -.03], p < .05). These results suggest that extracellular free water corresponds with concurrent levels and subsequent elevations of peripheral inflammatory cytokines from blood serum. These findings also convey a relationship between subjective cognitive concerns and age-related changes in extracellular FW in healthy older adults without deficits on neuropsychological assessment. The study provides insight into the relationship between subjective cognitive concerns and microstructural white matter changes as well as subtle changes in extracellular FW content before declines are observed on neuropsychological testing.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2024.285

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Available for download on Wednesday, May 20, 2026

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