Supplementary Material for: Associations between cardiovascular risk factors and cognitive function: a cross-sectional study of twins in the United Kingdom

Introduction: Cardiovascular risk factors (CVRF) have been associated with cognitive impairment; however, the underlying mechanisms remain unclear. This study used twins modelling, to investigate whether shared twin factors contribute to the associations between CVRFs and cognitive function.
Methods: This study used a cross-sectional design and participants were from the UK adult twin registry. Clinically validated cognitive tests were administered during routine clinical research visits between 2013 and 2016, measuring overall global cognition, recall, verbal fluency, processing speed, episodic memory and learning. CVRFs were total cholesterol (TC), high-density lipoprotein (HDL), systolic blood pressure (SBP), type 2 diabetes (T2D), and smoking status.
Results: Participants were between 1300-2300 twins (depending on the cognitive test) and the mean age of twins was approximately 56 years. Cholesterol levels (both TC and HDL) were significantly associated (p<0.05) with overall global cognition, recall, and verbal fluency with effect sizes (standardised) ranging from 0.5 to 0.11. In the twins modelling, after adjusting for genetic and shared environmental factors, the associations disappeared. Similarly, higher SBP levels were associated with poorer verbal fluency performance (-0.05 [-0.10 to 0.00]), and while between-pair effects were significant found (-0.09 [-0.15 to -0.03]), within-pair effects (after adjusting of shared environmental factors) were not.
Conclusion: Higher TC, HDL, and lower SBP were all associated with better performance on a range of validated cognitive tests. However, findings suggest that the association between CVRFs and cognitive function is predominantly explained by shared twin-pair factors which may be genetic or shared environment.