genetic studies in healthy young and elderly subjects, suggest that APOE-4, as a risk factor for AD, is associated with changes in the intrinsic functional organization of brain networks in cognitively normal carriers [31], [32], [78], [79], even in the absence of amyloid plaques [80], and with some degree of frontal and parietal disconnection at the stage of early AD. Patients with long-term and severe dementia, however, might show functional connectivity patterns determined by the cognitive level or disease-specific factors rather than by the APOE susceptibility gene.
