Memory impairment is the salient feature of Alzheimer's disease (AD) and is presumed to relate to hippocampal pathology. Other regions, however, such as posterior cingulate and adjacent association cortices, are also severely affected at an early stage. Paired associates learning (PAL) was expressly designed as a ‘hippoocampal’ test and has exquisite sensitivity to incipient AD. It is therefore assumed that this sensitivity reflects hippoocampal degeneration, although this has never been proven. This study investigated the neural underpinning of PAL performance in AD. If PAL performance related to non-hippocampal regions, a reappraisal of the nature of memory impairment in AD would be necessary. 31 patients with early AD were examined. Error score at the 6-pattern stage was regressed against grey matter density and FDG-PET. PAL performance correlated with hypometabolism in the right isthmus/retrosplenial region and reduced grey matter density of the right hippocampus. Memory impairment in AD may be more complex than previously thought. There was no evidence for a relationship between hippocampal atrophy and task performance in this study. The isthmus/retrosplenial region has been shown in previously work to be the most metabolically abnormal region in incipient AD—it may also contribute to memory impairment in AD.