Previous group studies using positron emission tomography to assess resting cerebral glucose metabolism in very early Alzheimer's disease and mild cognitive impairment have identified the posterior cingulate and adjacent cingulo-parietal cortex as the first isocortical area to develop hypometabolism. We studied the profile of resting cerebral glucose metabolism in individuals with mild cognitive impairment to assess whether more specific and stereotyped regional hypometabolism would be evident across subjects. The study found that the most consistently hypometabolic region between individual subjects was a subregion of the posterior cingulate, the retrosplenial cortex (BA 29/30). This result is discussed in the context of regional connectivity, focal lesion evidence and functional activation studies of episodic memory paradigms in both normal and Alzheimer's disease groups. We propose that the retrosplenial cortex may represent a key junction between prefrontal areas involved in implementing retrieval strategies for episodic memory and hippocampal-based mnemonic processing; we therefore interpret the retrosplenial hypometabolism as a probable contributor to the memory impairment seen in mild cognitive impairment by disconnecting these two anatomical networks.