Critical and non-critical connections not differently associated with either Alzheimer’s disease or vascular pathologies

Following observations from a pilot study that, contrary to expectations, indicated that critical white matter (WM) connections were not more vulnerable to either SVD or AD pathologies than non-critical connections, we set out to systematically evaluate the relation between these pathologies and both connections types. For patients with CADASIL (n=59), Mixed pathology (n=57) and autosomal dominant AD (ADAD; n=50) we reconstructed WM networks based on diffusion tensor imaging and subsequently defined critical and non-critical connections. Associations between AD markers (CSF Aβ⁴², p-tau levels, estimated years of onset (EYO)) and SVD markers (WM hyperintensity (WMH) volume) and both connection types were tested with linear regression analyses. WMH volume showed equally strong associations to the strength of both critical and non-critical connections. Aβ-positivity, Aβ⁴² levels, p-tau levels and EYO, while less strongly related to the strength of the WM connections, did consistently show similar effect sizes for both connection types. Sensitivity analyses using different definitions of connectivity yielded similar results. SVD burden influenced WM integrity more than AD, but we found no support for critical connections being more vulnerable to these disease effects than non-critical connections.