Spatial navigational abilities decline in aging and are one clue to the impact of aging on the brain. Research in the fields of aging and navigation has primarily assessed this problem with models that focus primarily on the focal impact of brain structures affected by aging and important for memory, such as the hippocampus. Yet, emerging cognitive neuroscience models suggest navigation is supported by a brain network including a visual-to-medial temporal lobe pathway, a visual-to-parietal cortex pathway, and areas of pathway integration in precuneus and retrosplenial cortex. Therefore, here I investigated the relationship between structural and functional brain network properties of this theoretical navigation network in cognitively normal older adults and their performance in two navigation conditions designed to probe different age-related memory systems: route learning (RL) and cognitive mapping (CM). We leveraged a navigation task known to be related to biomarkers of Alzheimer's disease (AD) and the longitudinal progression of AD. Importantly, AD changes in the brain are hypothesized to begin decades before diagnosis and the gold standard behavioral test is episodic memory. Leveraging an established navigation task, my objective was to test the relationship of structural and functional integrity of the navigation network with navigation performance, and the role of episodic memory in these relationships, which may be indicative of preclinical AD in cognitively normal older adults.

This research enhances our understanding of how age-related changes in brain structure and network properties impact spatial navigation in healthy aging. Specifically, the impact of aging on cognitive mapping abilities, structural integrity of the navigation network, and the reorganization of its functional connections. Leveraging an established task, results of my dissertation work expand on studies primarily using focal brain models to further stress the importance of network models in navigation across the lifespan. Importantly, network models of navigation underlying cognitive mapping have potential to aid in the early identification of individuals at risk of developing dementia, informing implementation of more targeted early intervention strategies.

In the first aim, atrophy in gray matter of the navigation network was associated with CM and episodic memory performance. Additionally, navigation network atrophy partially mediated the relationship between age and CM learning, but not episodic memory. No relationships were observed between the navigation network atrophy and RL performance. Moreover, exploratory analyses identified prefrontal regions related to CM, including the dorsolateral prefrontal cortex, orbital frontal cortex, and superior frontal gyrus (SFG).

In the third aim, functional connectivity and organization of the navigation network was associated with CM learning, but not with RL or episodic memory. Unlike brain structural measures, connectivity did not mediate the relationship between age and navigation or memory. Notably, we observed changes in the organization of the navigation network with aging. Specifically, the prefrontal cortex module merged with the visual-to-parietal module and the precuneus shifted its module affiliation to couple with the MTL.

In the second aim, white matter integrity in tracts connecting the hippocampus and broader medial temporal lobe (MTL) to prefrontal and parietal cortices was associated with CM and episodic memory learning, but not RL. The MTL-related tracts partially mediated both the relationship between age and CM and age and episodic memory. Further, exploratory analyses identified white matter integrity in tracts connecting the MTL, visual cortex, precuneus, and SFG associated with CM performance.