Cardiovascular disease (CVD) and cognitive decline are significant contributors to global mortality and morbidity. Physical activity (PA) has emerged as a modifiable factor with positive effects on various aspects of health across different age groups. While many studies has identified direct relationships between PA and cognition, PA and CVD risk factors, and cognition and CVD risk factors, limited research has investigated the potential mediating role of CVD risk factors in the relationship between PA and cognition, particularly among older adults. This thesis aimed to fill this gap by utilizing a cross-sectional study design and secondary analysis of data from the Women’s Advanced Risk-Assessment in Manitoba (WARM) Hearts cardiovascular screening study. The study explored the mediating role of both composite and individual CVD risk factors on the association between PA and cognition in community-dwelling middle-aged and older females. Mediation analysis was conducted using the PROCESS macro (version 4.3) for SPSS. PA and specifically moderate to vigorous PA (MVPA) was associated with cognitive performance through body mass index (BMI) and frailty index (FI), but not through a composite CVD risk factor or other individual CVD risk factors, such as systolic blood pressure (BP), diastolic BP, arterial stiffness, and blood markers. The lack of significant mediating effects of CVD-specific risk factors suggests that the cognitive benefits of PA, particularly MVPA, may be more strongly linked to general health indicators such as BMI and FI rather than through CVD-specific pathways. These results imply that older females may see cognitive benefits through the maintenance of BMI and FI by engaging in PA and specifically MVPA. By investigating these relationships, this thesis provided insights into the mechanisms underlying the association between PA, cognition, and CVD risk factors in middle-aged and older females. The findings may inform interventions aimed at promoting cognitive and overall health in this population, emphasizing the importance of regular engagement in PA.