Document Type



Doctor of Philosophy



Date of Defense


Graduate Advisor

Robert Paul, PhD


Berit Brogaard

Steve Bruce

Michael Griffin


The current study sought to understand relationships between insulin resistance (IR), diffusion tensor imaging (DTI), and cognitive performance. It was hypothesized that IR would have a negative impact upon white matter and cognition. It was predicted that the uncinate fasciculus would be the most severely impacted, and this in turn would affect executive function and memory. Aim: The purpose of the study was to determine the impact of IR on white matter brain integrity among cognitively normal older adults using DTI and neuropsychological test performance. Background: The prevalence of IR has increased with growing incidence of obesity and older aged adults. IR is associated with increased risk for dementia. Studies focused on the effects of IR on cognition report impairments in memory (Bruehl, Sweat, & Hassenstab, 2010), and executive function (Abbatecola, Paolisso, & Lamponi, 2004). Neuroimaging studies have revealed IR is related to development of stroke in subcortical white matter (Kario, Matsuo, Kobayashi, Hoshide, & Shimada, 2001), and increased atherosclerosis (Park & Kwon, 2008). Despite the noted relationships between IR and brain integrity, few studies have investigated the impact of IR by combining neuroimaging and neuropsychological batteries among otherwise healthy adults, and no studies have examined the microstructural integrity of the brain specific to IR using DTI. Hypothesis: Older individuals with IR would exhibit compromised DTI metrics on fractional anisotropy (FA) and mean diffusivity (MD) in the uncinate fasciculus, and perform significantly worse on tests of memory and executive function. Methods: Forty-six individuals aged 53-79 years were evaluated using the QUICKI algorithm to determine IR level. Individuals underwent a 3 Tesla DTI scan and neuropsychological tests. MD and FA were calculated for the uncinate fasciculus. Results: After controlling for education, IR status was significant for list learning (p<.01). However, IR was not significant for DTI scalar metrics of the uncinate fasciculus or measures of executive function. Conclusion: These findings indicate IR has negative consequences for tasks that involve learning, but not with measures of executive function. Future studies are necessary to investigate the relation of IR to other white matter tracts in the brain.

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