ORCID ID
Graduation Date
Summer 8-14-2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Programs
Pharmacology and Experimental Neuroscience
First Advisor
David Warren
Abstract
Childhood is a neurodevelopmental period during which foundational structural, functional, and cognitive maturation occurs. Due to critical windows and sensitive periods, the developing brain is highly susceptible to external stressors that can alter neurodevelopmental trajectories and produce lasting effects into adulthood. Of particular interest are brain and cognitive variables that are especially vulnerable to Alzheimer’s disease, including the hippocampus and relational memory. Alzheimer’s disease is a devastating, incurable, neurodegenerative disorder with several established risk factors, including stress. However, it remains unclear whether exposure to stress during childhood increases vulnerability or resilience to Alzheimer’s disease-related outcomes. This study used data from the Polygenic Risk of Alzheimer’s disease in Nebraska Kids (PRANK) and PRANK-eXposome (PRANK-X) studies to examine associations between psychosocial stress and brain and cognitive variables known to be affected in Alzheimer’s disease. This work investigated the neural mechanisms supporting relational memory during adolescence and examined whether psychosocial stress is associated with variations in relational memory performance and hippocampal structure. First, the patterns of cortical activation underlying relational memory encoding were characterized, with a particular focus on the hippocampus. Next, associations between psychosocial stress and 1) relational memory performance and 2) hippocampal subfield volumes were evaluated. Successful relational encoding was associated with activation in cortical regions, including the hippocampus. While the stress variables were not associated with relational memory performance, socioeconomic stress was associated with left dentate gyrus volume. Taken together, these findings demonstrate that while stress may not affect cognitive performance in this adolescent sample, alterations in brain structure, particularly in the hippocampus, may be occurring beneath the surface. These results suggest that childhood stress may influence neurobiological systems relevant to Alzheimer’s disease. Further research is needed to understand if this difference in subfield volume is a harmless variant of neurodevelopment or if it functions as a seed for later neurodegenerative disease risk.
Rights
The author holds the copyright to this work and any reuse or permissions must be obtained from the author directly.
Recommended Citation
Ramirez, Meghan, "Through the Looking Glass: A Neurodevelopmental Perspective on Alzheimer's Disease-Vulnerable Brain and Cognitive Systems" (2026). Theses & Dissertations. 1092.
https://digitalcommons.unmc.edu/etd/1092