Functional imaging methods such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) allow in vivo assessment of cerebral metabolism at rest and cerebral responses to cognitive stimuli. Activation studies with different cognitive tasks have deepened the understanding of underlying pathology leading to Alzheimer disease (AD) and how the brain reacts to and potentially compensates the imposed damage inflicted by this disease. The aim of this manuscript study was to summarize current findings of activation studies in healthy people at risk for AD, in people with mild cognitive impairment (MCI) as a possible progenitor of AD and finally in patients with manifest AD, adding recent results about impaired deactivation abilities and default mode function in AD. A new comprehensive model will be introduced integrating these heterogeneous findings and explaining their impact on cognitive performance.