Alterations of the brain functional organization in young-onset Alzheimer's disease: Is it a matter of “time”?

Compared with more typical late-onset Alzheimer's disease (AD), the mechanisms of young-onset AD (YOAD; age of symptom onset <65 years) remain less understood. Using resting-state functional MRI data and dynamic causal modeling techniques, Sacu et al. demonstrate that individuals with YOAD (amnestic AD or posterior cortical atrophy) exhibit alterations in effective (i.e., directed) connectivity involving key cortical nodes of the brain's default mode network. Interpretation of the authors' findings may benefit from considering disease progression as a temporal factor and a framework to conceptualize brain connectivity changes as a dynamic, non-linear process that evolves across disease stages.