This Research Topic aims to encourage the proposal of state-of-the-art methodologies related to CWAS techniques and their applications to neurodegenerative disorders. A total of five studies collected in this topic mainly cover (1) advanced statistical methods to avoid multiple covariates in analyzing brain connectivity; (2) a data-driven CWAS design to clarify and validate brain network findings associated with aging in a large sample of subjects; (3) a virtual analytical approach to describe brain disconnectome reorganization while avoiding the issue of artifacts that are prone to occur in the presence of white matter hyperintensity; (4) advanced dynamic connectivity measurements as novel brain imaging markers to discriminate AD patients at different stages; and (5) the brain structural covariance network analysis and related novel statistical model to unravel pathological progression of AD. In what follows, we summarized the highlights the methodologies and applications in aging and related neurodegeneration of each article.