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It is currently unclear whether these early disease stages are associated with a progressive disruption in the communication between brain regions that subsequently leads to cognitive decline and dementia.
We combined graph theory with diffusion tensor imaging to investigate integration, segregation, and centrality measures in the brain connectome in the previous groups. Altogether, our findings suggest that amyloid pathology is not sufficient to disrupt structural network topology, whereas neurodegeneration is. These disappointing results suggest that perhaps the pathological mechanisms are being targeted at the wrong stage of the disease, when it is too late to reverse any neurodegenerative processes or halt disease progression.
Indeed, there is increasing evidence showing that the pathological changes in AD begin well before clinical symptoms by several years to decades Villemagne et al. Hence, a better understanding of this preclinical period is crucial to identify early signs of the disease and treat it successfully. Recently, a model describing the temporal evolution of the pathological processes occurring in the preclinical period of AD has been proposed Jack et al. Hence, the clinical symptoms of AD are just the final manifestation of a long-standing disease process during which multiple pathological changes take place in the brain.
Imaging techniques offer an invaluable tool to assess brain pathology in vivo. In particular, brain connectivity measures are thought to represent reliable biomarkers that reflect downstream cognitive deficits and upstream neuronal dysfunction and disease spread Seeley et al.
