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Topic

Investigating Influential Factors on Neurocognitive Aging in Women With and Without Multiple Sclerosis

Department of Psychology

Date & location

• Friday, February 27, 2026
• 11:30 A.M.
• Virtual Defence

Examining Committee

Supervisory Committee

• Dr. Jodie Gawryluk, Department of Psychology, ̽��ϵ�� (Supervisor)
• Dr. Jonathan Rush, Department of Psychology, UVic (Member)
• Dr. David Kennedy, School of Exercise Science, Physical and Health Education, UVic (Outside Member)

External Examiner

• Dr. Jelena King, Department of Psychiatry and Behavioural Neurosciences, McMaster University

Chair of Oral Examination

• Dr. Barbara Hawkins, Department of Biology, UVic

Abstract

As the global aging population rises, understanding the complexities of neurocognitive aging has become an increasingly important topic of study. Among aging adults, women in particular face unique challenges due to reproductive aging and a disproportionate burden of chronic health conditions, such as Multiple Sclerosis (MS). Despite these challenges, women have been historically underrepresented in neurocognitive aging research. As a result, there is limited understanding of how neurocognitive functioning and brain structure change in aging women, and how these processes are influenced by health-related factors such as hormone replacement therapy (HRT) and physical activity (PA). This dissertation takes a multimodal MRI and cognitive assessment approach across three complementary studies to investigate factors influencing neurocognitive aging in women.

Study 1 examined the influence of biological sex, and influences of self-reported PA, on brain structure and cognitive performance in a large cohort of healthy older adults from the UK Biobank. Findings revealed significant sex effects, where females demonstrated higher total GMV but smaller volumes in specific regions such as the frontal poles, thalamus, and hippocampus. Cognitive performance also varied by sex, with females outperforming males on attention and visual memory tasks, while males showed higher working memory and fluid intelligence performance. PA moderated the relationship between sex and white matter microstructure in the corpus callosum and superior longitudinal fasciculus.

Study 2 refined the prior sample to postmenopausal women only to examine whether HRT use, and its interaction with PA, influenced brain structure and cognitive function. Women with a history of HRT use exhibited reduced GMV and WMI, as well as worse performance on executive functioning, working memory, and processing speed tasks compared to non-users. PA moderated white matter outcomes differently in HRT users and non-users, suggesting complex iv interactions between hormonal and PA interventions.

Study 3 extended the investigation to a clinical sample of aging women with MS, using similar MRI and cognitive metrics, to explore within-group neurocognitive characteristics. Results showed higher white matter microstructure in multiple white matter tracts was associated with better verbal memory, visuospatial memory, and processing speed/working memory. GMV was positively associated with visuospatial memory. PA moderated the relationships between brain structure and cognitive outcomes, particularly for verbal memory and working memory.

Together, these findings underscore the complex interplay between sex, hormones, PA, and disease in shaping neurocognitive aging trajectories in women. Ongoing research incorporating women’s health factors is critical for understanding underlying neural mechanisms of cognitive aging, along with modifiable lifestyle factors, like PA, to inform intervention strategies that support healthier brain aging in women.