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

INSERM E0218-Université de Caen, Laboratoire de Neuropsychologie, CHU Côte de Nacre,14033 Caen cedex, France.
Brain (Impact Factor: 10.23). 10/2003; 126(Pt 9):1955-67. DOI: 10.1093/brain/awg196
Source: PubMed

ABSTRACT 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.

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    • "Neuropsychological tests were administered to all participants to assess their cognitive abilities: two tests of verbal and visual episodic memory processes that had previously been developed in our laboratory, based on the Encoding, Storage, Retrieval (ESR) paradigm (Chetelat et al., 2003; Eustache, Desgranges, & Lalevée, 1998; Fouquet et al., 2012), the Digit Span Backward, Letter-Number Sequencing and Arithmetic subtests of the Wechsler Adult Intelligence Scale (WAIS; Wechsler, 2008), the Trail Making Test (TMT) Parts A and B (Reitan, 1992), formal and semantic verbal fluency (Cardebat, Doyon, Puel, Goulet, & Joanette, 1990), and the d2 Test of Attention (Brickenkamp & Zillmer, 1998). "
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    • "Consistent with this hypothesis, neuroimaging studies of episodic anterograde memory in MCI have shown the involvement of specific structures of the core network. For instance, an association has been found between the metabolism of the posterior cingulate cortex and episodic memory performance in MCI (Bastin et al., 2010; Chételat et al., 2003). Furthermore, controlled retrieval of episodic information in MCI patients has been related to metabolic activity in the dorsomedial prefrontal cortex (Bastin et al., 2010). "
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    • "As pointed out by cognitivo-metabolic correlation studies (Desgranges et al., 1998; for review, see Salmon et al., 2008), the functional disturbance of this limbic structure is highly linked to the patients' episodic memory deficit. This approach has also highlighted other regions responsible for episodic memory deficits in the earlier stages of the disease, such as the posterior cingulate cortex (Chételat et al., 2003). Task-related functional brain imaging techniques have been used to further investigate the substrate of episodic impairment in AD. "
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