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Rhinal hypometabolism on FDG PET in healthy APO-E4 carriers: impact on memory function and metabolic networks

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The ε4 allele of the apolipoprotein E (APO-E4) gene, a genetic risk factor for Alzheimer’s disease (AD), also modulates brain metabolism and function in healthy subjects. The aim of the present study was to explore cerebral metabolism using FDG PET in healthy APO-E4 carriers by comparing cognitively normal APO-E4 carriers to noncarriers and to assess if patterns of metabolism are correlated with performance on cognitive tasks. Moreover, metabolic connectivity patterns were established in order to assess if the organization of neural networks is influenced by genetic factors.

Methods

Whole-brain PET statistical analysis was performed at voxel-level using SPM8 with a threshold of p < 0.005, corrected for volume, with age, gender and level of education as nuisance variables. Significant hypometabolism between APO-E4 carriers (n = 11) and noncarriers (n = 30) was first determined. Mean metabolic values with clinical/neuropsychological data were extracted at the individual level, and correlations were searched using Spearman’s rank test in the whole group. To evaluate metabolic connectivity from metabolic cluster(s) previously identified in the intergroup comparison, voxel-wise interregional correlation analysis (IRCA) was performed between groups of subjects.

Results

APO-E4 carriers had reduced metabolism within the left anterior medial temporal lobe (MTL), where neuropathological changes first appear in AD, including the entorhinal and perirhinal cortices. A correlation between metabolism in this area and performance on the DMS48 (delayed matching to sample-48 items) was found, in line with converging evidence involving the perirhinal cortex in object-based memory. Finally, a voxel-wise IRCA revealed stronger metabolic connectivity of the MTL cluster with neocortical frontoparietal regions in carriers than in noncarriers, suggesting compensatory metabolic networks.

Conclusion

Exploring cerebral metabolism using FDG PET can contribute to a better understanding of the influence of genetic factors on cerebral metabolism at both the local and network levels leading to phenotypical variations of the healthy brain and selective vulnerability.

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Compliance with ethical standards

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Conflicts of interest

None.

Funding

This study was funded by AP-HM (PHRC 2007/09) and supported by INSERM (Centre d’Investigation Clinique, CIC, Hôpital de la Conception, Marseille), as well as the association “Déchaîne ton cœur”. M. Didic received a Marie Curie grant from the European Commission (BMH4CT965032).

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. A committee on human experimentation of the institution and the local institutional committee approved this study (registration number NCT00484523).

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Authors and Affiliations

  1. Service de Neurologie and Neuropsychologie, Pôle de Neurosciences Cliniques, Centre Hospitalo-Universitaire de la Timone, AP-HM, Marseille, France

    Mira Didic, Olivier Felician, Natalina Gour & Mathieu Ceccaldi

  2. Aix Marseille Université, Inserm, INS UMR_S 1106, 13005, Marseille, France

    Mira Didic, Olivier Felician, Natalina Gour & Mathieu Ceccaldi

  3. Département de Génétique Médicale, Centre Hospitalo-Universitaire de la Timone, AP-HM, and INSERM UMR_S 910: “Génétique Médicale et Génomique fonctionnelle”, Marseille, France

    Rafaelle Bernard & Christophe Pécheux

  4. Service Central de Biophysique et Médecine Nucléaire, Centre Hospitalo-Universitaire de la Timone, AP-HM, 13005, Marseille, France

    Olivier Mundler & Eric Guedj

  5. Aix Marseille Université, CERIMED, CNRS UMR7289, INT, 13005, Marseille, France

    Olivier Mundler & Eric Guedj

  6. Aix Marseille Université, CNRS UMR7289, INT, 13005, Marseille, France

    Olivier Mundler & Eric Guedj

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  1. Mira Didic
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  2. Olivier Felician
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Didic, M., Felician, O., Gour, N. et al. Rhinal hypometabolism on FDG PET in healthy APO-E4 carriers: impact on memory function and metabolic networks. Eur J Nucl Med Mol Imaging 42, 1512–1521 (2015). https://doi.org/10.1007/s00259-015-3057-y

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