Associations of white matter hyperintensities with networks of grey matter blood flow and volume in midlife adults: a CARDIA MRI substudy

White matter hyperintensities (WMHs) are emblematic of cerebral small vessel disease, yet characterization at midlife is poorly studied. Here, we investigated whether WMH volume is associated with brain network alterations in midlife adults. 254 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study were selected and stratified by WMH burden yielding two groups of equal size (Lo- and Hi-WMH groups). We constructed group-level covariance networks based on cerebral blood flow (CBF) and grey matter volume (GMV) maps across 74 grey matter regions. Through consensus clustering, we found that both CBF and GMV covariance networks were partitioned into modules that were largely consistent between groups. Next, CBF and GMV covariance network topologies were compared between Lo- and Hi-WMH groups at global (clustering coefficient, characteristic path length, global efficiency) and regional (degree, betweenness centrality, local efficiency) levels. At the global level, there were no group differences in either CBF or GMV covariance networks. In contrast, we found group differences in the regional degree, betweenness centrality, and local efficiency of several brain regions in both CBF and GMV covariance networks. Overall, CBF and GMV covariance analyses provide evidence of WMH-related network alterations that were observed at midlife.