Recent work suggests that aberrant functional neurocircuitries arise prior to significant structural atrophy and clinically cognitive deficits in dementia. Using a rigorous, longitudinally confirmed multi-domain amnestic MCI cohort we show that functional decoupling of networks implicated in memory and executive function, occur prior to measurable MTL atrophy in this population. Moreover, we show that decreased functional connectivity in these networks is associated with poorer cognitive performance. Further longitudinal studies investigating the neuronal underpinnings of disease progression will provide insight into potential functional biomarkers and establish significance of functional decoupling within the sequential model of dynamic biomarkers of Alzheimer’s pathological cascade.
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