Background Alzheimer's disease is a neurodegenerative disease with progressive cognitive impairments that are likely to affect the compensatory mechanisms and the cerebral activation patterns of the patients. Methods Functional neuroimaging was used to test the effect of disease severity on the brain activation of persons at risk for Alzheimer's disease and to highlight the process of compensation in some of these individuals. This was done for the verbal learning of either semantically related or semantically unrelated word pairs. Twenty-six persons with mild cognitive impairment (MCI) were separated into two groups, MCI higher-cognition and MCI lower-cognition, with a split-median on their scores for the Mattis Dementia Rating Scale. A group of 14 healthy older adults were matched to the MCI participants. Results In both task conditions, MCI higher-cognition activated additional regions, relative to control subjects, in the right ventrolateral and dorsolateral prefrontal brain areas. Additional areas of hyperactivation were found in the right prefrontal area 45 when encoding semantically related word pairs and in the left hippocampus during encoding of unrelated word pairs. In contrast, MCI lower-cognition failed to show additional prefrontal activations when compared with healthy control subjects and showed decreased activation in posterior areas. Conclusions These results are in line with compensation occurring at the beginning of the MCI continuum and with the breakdown of compensation in patients experiencing more severe symptoms.