Shorey, Carrie2025-08-202025-08-202025-08-202025-08-18https://hdl.handle.net/10012/22221Background Cognitive impairment and its risk factors are a growing global concern, particularly among understudied populations such as immigrants. Physical health, psychosocial, and mental health stressors (“stress”) are all linked to poorer cognitive function. While immigrants are more likely than non-immigrants to experience adverse effects of stress, likely due to greater exposure to stressors, they may also experience unique psychosocial and mental health stressors. At the same time, they may benefit from physical health protective factors such as the “healthy immigrant effect”. However, whether their distinct stress profile increases their vulnerability to cognitive impairment remains unclear and was therefore the key focus of this dissertation. Further, because stress can elevate systemic inflammation, this research examined whether inflammation mediated the association between stress and cognitive function. The role of sex in this association was also explored, as immigrant women often experience higher levels of stress, which may amplify inflammatory responses and contribute to worse cognitive outcomes compared to immigrant men and non-immigrants. Methods All studies used data from the Canadian Longitudinal Study on Aging’s (CLSA) Comprehensive cohort, a prospective, population-based study of Canadians aged 45-85 at baseline (n = 30,097, including 5,449 immigrants). Structural equation models examined the association between baseline physical health (measured by physical health conditions), psychosocial (measured by barriers to social activities, financial need, and housing problems), and mental health (measured by psychological distress) stressors with executive function and memory at baseline and three-year follow-up. Analyses were stratified by immigrant status and sex, with inflammation (measured by C-reactive protein; CRP) tested as a potential mediator. Models were adjusted for age, education, and congruence between the participant’s first language learned and the language of the cognitive testing. Results Study 1: Physical health stress. Negative associations of physical health conditions with executive function and episodic memory were more consistent among non-immigrants than immigrants. In non-immigrants, significant negative associations were observed at both baseline and follow-up, whereas among immigrants, effects varied by sex. While immigrant women showed no association between physical health conditions and baseline episodic memory, they exhibited significant associations with all other cognitive outcomes. In contrast, for immigrant men, physical health conditions were only associated with baseline episodic memory and not with any other cognitive outcomes. These findings suggest that stress related to physical health conditions had a more limited role in cognitive outcomes for immigrant men compared to immigrant women and non-immigrant women and men. Although CRP significantly mediated some associations, the effects were clinically negligible. Study 2: Psychosocial stress. Associations of psychosocial stress with executive function and episodic memory were observed in both immigrants and non-immigrants. However, immigrant women were the least likely to show significant associations between psychosocial stress and cognitive outcomes, while immigrant men were the most likely, showing stronger associations than immigrant women and non-immigrant women and men across all of the cognitive domains and time points. This pattern highlights the disproportionate impact of psychosocial stress on cognitive outcomes among immigrant men. While there were statistically significant mediations by CRP, they were clinically negligible. Study 3: Mental health stress. Negative associations of psychological distress with executive function and episodic memory were observed in both immigrants and non-immigrants. However, immigrant women and men experienced more pronounced associations between psychological distress and baseline executive function than non-immigrant women and men. Notably, immigrant men also showed a strong association with baseline episodic memory, further emphasizing their susceptibility to the effects of mental health stress on cognition. While there were statistically significant mediations by CRP, they were clinically negligible. Contribution To our knowledge, no previous studies globally have measured the complex effects of stress and inflammation on cognition in aging immigrants. The findings align with the “healthy immigrant effect” as, despite physical health conditions being generally similar between immigrants and non-immigrants, their impact on cognition was greater among non-immigrants. This suggests that while stress related to physical health conditions was less strongly linked to cognition in immigrants, psychosocial and mental health stress may be more strongly associated with cognitive outcomes in this group. Notably, immigrant men were the most likely to show significant negative associations of psychosocial and mental health stressors with cognition, highlighting their particular vulnerability and a potential area for targeted intervention. While stress-related cognitive vulnerabilities were evident across all of the groups, the strength and consistency of these associations varied, suggesting that certain subgroups may be more vulnerable to stress and may benefit from targeted support. Although CRP significantly mediated some associations across all categories of stressors, the effects were consistently negligible, suggesting that systemic inflammation, as measured by baseline CRP, was not the primary mechanism linking chronic stress to cognition in these studies. By providing much-needed data on a diverse immigrant population—unlike much of the existing literature, which focuses on more homogeneous groups—these studies contribute to a broader global understanding of how stress impacts cognitive function in aging adults, with implications for public health and policy across different immigration contexts.enimmigrantsstresscognitive functionaginginflammationCLSADoctoral Thesis