Graph theory is increasingly being used to study brain connectivity across the spectrum of Alzheimer's disease (AD), but prior findings have been inconsistent, likely reflecting methodological differences. We systematically investigated how methods of graph creation (i.e., type of correlation matrix and edge weighting) affect structural network properties and group differences. We estimated the structural connectivity of brain networks based on correlation maps of cortical thickness obtained from MRI. Four groups were compared: 126 cognitively normal older adults, 103 individuals with Mild Cognitive Impairment (MCI) who retained MCI status for at least 3 years (stable MCI), 108 individuals with MCI who progressed to AD-dementia within 3 years (progressive MCI), and 105 individuals with AD-dementia. Small-world measures of connectivity (characteristic path length and clustering coefficient) differed across groups, consistent with prior studies. Groups were best discriminated by the Randić index, which measures the degree to which highly connected nodes connect to other highly connected nodes. The Randić index differentiated the stable and progressive MCI groups, suggesting that it might be useful for tracking and predicting the progression of AD. Notably, however, the magnitude and direction of group differences in all three measures were dependent on the method of graph creation, indicating that it is crucial to take into account how graphs are constructed when interpreting differences across diagnostic groups and studies. The algebraic connectivity measures showed few group differences, independent of the method of graph construction, suggesting that global connectivity as it relates to node degree is not altered in early AD.
Given a sequence of observations, has a change occurred in the underlying probability distribution with respect to observation order? This problem of detecting change points arises in a variety of applications including health prognostics for mechanical systems, syndromic disease surveillance in geographically dispersed populations, anomaly detection in information networks, and multivariate process control in general. Detecting change points in high-dimensional settings is challenging, and most change-point methods for multidimensional problems rely upon distributional assumptions or the use of observation history to model probability distributions. We present three new nonparametric statistical tests for heterogeneity based on the combinatorial properties of minimum non-bipartite matching (MNBM). The key idea underlying each of these tests is that if a sequence of independent random observations undergoes a change in distribution-either an abrupt "shift" or a gradual "drift"-a MNBM based on inter-point distances tends to produce pairings that are closer in the sequence labeling than would be the case if the observations were drawn from the same distribution. Our tests follow on the work of Rosenbaum (2005) who used MNBM to derive a simple cross-match test statistic for the two-sample problem based on this idea. Similar ideas are present in the minimum spanning tree (MST) test derived by Rafsky (1979, 1981). We extend these approaches by utilizing ensembles of orthogonal MNBMs which greatly increase information extraction from the data, leading to tests that compare favorably to parametric procedures while maintaining level and good power properties across distributions.
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