Association of structural connectivity with functional brain network segregation in a middle-aged to elderly population

Introduction The deterioration of white matter pathways is one of the hallmarks of the ageing brain. In theory, this decrease in structural integrity leads to disconnection between regions of brain networks and thus to altered functional connectivity and a decrease in cognitive abilities. However, in many studies, associations between structural and functional connectivity are rather weak or not observed at all. System segregation, defined as the extent of partitioning between different resting state networks has increasingly gained attention in recent years as a new metric for functional changes in the aging brain. Yet there is a shortage of previous reports describing the association of structural integrity and functional segregation.Methods Therefore, we used a large a large sample of 2,657 participants from the Hamburg City Health Study, a prospective population-based study including participants aged 46-78 years from the metropolitan region Hamburg, Germany. We reconstructed structural and functional connectomes to analyze whether there is an association between age-related differences in structural connectivity and functional segregation, and whether this association is stronger than between structural connectivity and functional connectivity. In a second step, we investigated the relationship between functional segregation and executive cognitive function and tested whether this association is stronger than that between functional connectivity and executive cognitive function.Results We found a significant age-independent association between decreasing structural connectivity and decreasing functional segregation across the brain. In addition, decreasing functional segregation showed an association with decreasing executive cognitive function. On the contrary, no such association was observed between functional connectivity and structural connectivity or executive function.Discussion These results indicate that the segregation metric is a more sensitive biomarker of cognitive ageing than functional connectivity at the global level and offers a unique and more complementary network-based explanation.