Access Type
Open Access Dissertation
Date of Award
January 2024
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Psychology
First Advisor
Jessica S. Damoiseaux
Abstract
Plasma neurofilament light (NfL) is a promising biomarker for monitoring and predicting cognitive function and neurodegeneration in Alzheimer’s disease (AD). However, the field still needs a better understanding of what plasma NfL reflects about neurodegenerative and cognitive changes occurring in AD, especially in the early stages of Alzheimer’s disease, for the optimized use of plasma NfL as a biomarker for AD for clinical and research purposes. Therefore, here I investigated how NfL is associated with memory function, the functional connectivity of the default mode network, and the microstructural properties of white matter and gray matter regions vulnerable to Alzheimer’s pathologies in older adults with normal cognition to mildly declined cognition likely due to Alzheimer’s disease. Furthermore, I examined how the association between NfL and white matter and gray matter microstructural characteristics differ depending on memory performance. I found that higher plasma NfL was associated with lower neurite density in white matter regions in anterior temporal, parietal, and superior frontal regions and lower fiber orientation dispersion in white matter regions with abundant crossing fibers in older adults with and without cognitive decline. Higher plasma NfL was also associated with lower neurite density in the entorhinal cortex in older adults with lower memory function, but not in those with higher memory function. However, plasma NfL was not associated with the functional connectivity within the posterior midline DMN subnetwork, as well as the functional connectivity between the posterior midline DMN and other DMN subregions. The findings of these studies provide knowledge that enhances the understanding of plasma NfL as a marker tracking the severity of cognitive decline and neurodegenerative changes in the early stages of AD, illuminating the differential sensitivity of plasma NfL to different aspects of neurodegenerative changes. These findings would contribute to future research to develop accurate disease prediction models using biomarkers including plasma NfL, as well as to future investigations to clarify the mechanisms of neurodegeneration and cognitive decline in AD using NfL.
Recommended Citation
Jung, Youjin, "Plasma Neurofilament Light As A Biomarker Of Neurodegeneration And Memory Function In Older Adults" (2024). Wayne State University Dissertations. 3971.
https://digitalcommons.wayne.edu/oa_dissertations/3971
