Vascular risk factors modulate gender-specific aging of brain white matter structural network

Vascular risk factors (VRFs) are known to increase risk for cerebrovascular disease and dementia, such as Alzheimers disease that is described as a dysconnectivity syndrome. The gender-related evidence on associations between VRFs and white matter (WM) structural network in large community-dwelling populations across middle and older age will contribute to understanding the biological underpinnings of sex and gender considerations in dementia. Based on 17,954 participants from the UK Biobank, we present the relationship between VRFs and WM network architecture (measured with network integration and segregation) in different gender groups. First, females exhibit lower network architecture and experience an accelerated decline earlier than males. Second, network integration is more sensitive to VRFs than segregation, with diabetes, hypertension, and excessive alcohol consumption having the greatest impact. Third, we found greater susceptibility of network architecture to VRFs in males, as well as female-preferred effects on regional integration of obesity, particularly on the subcortical structure and occipital lobe. Finally, higher combined risk was associated with more disrupted network architecture particularly on temporal and frontal lobe, as well as lower processing speed and working memory in both genders. Our findings provide new insights into understanding the relationship between VRFs and WM network architecture, guiding interventions to promote successfully cognitive aging and highlighting the importance of considering gender-specific effects in future research.