Background: Alzheimer's disease (AD) as a disconnection syndrome which disrupts both
brain information sharing and memory binding functions. The extent to which these two phenotypic expressions
share pathophysiological mechanisms remains unknown.
Objective: To unveil the electrophysiological correlates of integrative memory impairments in AD towards
new memory biomarkers for its prodromal stages.
Methods: Patients with 100% risk of familial AD (FAD) and healthy controls underwent assessment
with the Visual Short-Term Memory binding test (VSTMBT) while we recorded their EEG. We applied
a novel brain connectivity method (Weighted Symbolic Mutual Information) to EEG data.
Results: Patients showed significant deficits during the VSTMBT. A reduction of brain connectivity
was observed during resting as well as during correct VSTM binding, particularly over frontal and posterior
regions. An increase of connectivity was found during VSTM binding performance over central
regions. While decreased connectivity was found in cases in more advanced stages of FAD, increased
brain connectivity appeared in cases in earlier stages. Such altered patterns of task-related connectivity
were found in 89% of the assessed patients.
Conclusions: VSTM binding in the prodromal stages of FAD are associated to altered patterns of brain
connectivity thus confirming the link between integrative memory deficits and impaired brain information
sharing in prodromal FAD. While significant loss of brain connectivity seems to be a feature of the
advanced stages of FAD increased brain connectivity characterizes its earlier stages. These findings are
discussed in the light of recent proposals about the earliest pathophysiological mechanisms of AD and
their clinical expression.