UC Santa Barbara

Spatial navigation is a complex cognitive skill and multisensory process with large individual and sex differences, and deficits in navigational abilities are apparent in older adults (ages 65+ years). When in the aging process these changes first emerge is unclear. Further, little is known about whether endocrine aging during the midlife transition to menopause (ages ~45-55 years) impacts navigation behavior and the neural circuitry that processes spatial information. Given accumulating evidence of the overlapping neural circuitries that are sensitive to cognitive aging, enriched with sex hormone receptors, and support spatial navigation abilities, this represents a critical gap in our knowledge for how the brain’s navigational system changes with age.

In this dissertation, the three main lines of inquiry that are addressed are: (1) whether spatial navigation abilities and strategies change early in the aging process; (2) whether endocrine changes that occur during the menopausal transition are associated with spatial navigation abilities and strategies; and (3) whether endocrine changes during endocrine aging alter the brain’s navigation circuitry. To execute this, three virtual reality paradigms testing distinct aspects of spatial navigation were used in conjunction with structural magnetic resonance imaging. The results provide evidence that: (1) age-related changes in some aspects of navigation emerge as early as midlife; (2) spatial strategy is influenced by endocrine aging in women; and (3) age-related changes during endocrine aging impact the neural circuitry that supports spatial navigation performance.

By studying the brain’s navigational system from a women’s health perspective, this dissertation work provides novel insight into the biological factors that influence spatial navigation. These findings will inform future studies investigating the utility of spatial navigation as a behavioral marker for the early detection of individuals at risk for neurodegenerative disease. Women make up about two-thirds of patients living with Alzheimer’s disease, suggesting that sex-specific factors are crucial to understanding disease risk.