Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment

The present study aims to unravel, in the same study, both morphological and functional specific substrates of encoding versus retrieval deficits in patients with amnestic mild cognitive impairment (MCI). For this purpose, 21 highly screened MCI patients with isolated memory impairment, who attended a memory clinic and fulfilled operational criteria for MCI, underwent (i) two episodic memory subtests designed to assess preferentially either incidental encoding or retrieval capacity; (ii) a high-resolution T1-weighted volume MRI scan; and (iii) a resting state [18F]fluoro-2-deoxy-D-glucose PET study. Using statistical parametric mapping, positive correlations between memory scores on one hand, and grey matter density and normalized partial volume effect-corrected brain glucose utilization (ncCMRglc) on the other hand, were computed. Deficits in both encoding and retrieval were correlated with declines in hippocampal region grey matter density. The encoding subtest also correlated with hippocampal ncCMRglc, whereas the retrieval subtest correlated with the posterior cingulate area ncCMRglc only. The present findings highlight a distinction in the neural substrates of encoding and retrieval deficits in MCI. Furthermore, they unravel a partial dissociation between metabolic and structural correlates, suggesting distinct interpretations. Hippocampal atrophy was related to both encoding and retrieval deficits, possibly reflecting a direct effect on hippocampal functioning, as well as an indirect effect, through remote functional disruption, on posterior cingulate region synaptic function, respectively.