title: Rhinal hypometabolism on FDG PET in healthy APO-E4 carriers: impact on memory function and metabolic networks.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service de Neurologie and Neuropsychologie, Pôle de Neurosciences Cliniques, Centre Hospitalo-Universitaire de la Timone, AP-HM, Marseille, France, mira.didic@ap-hm.fr.
authors.forename: Mira
authors.initials: M
authors.lastname: Didic
authors.forename: Olivier
authors.initials: O
authors.lastname: Felician
authors.forename: Natalina
authors.initials: N
authors.lastname: Gour
authors.forename: Rafaelle
authors.initials: R
authors.lastname: Bernard
authors.forename: Christophe
authors.initials: C
authors.lastname: Pécheux
authors.forename: Olivier
authors.initials: O
authors.lastname: Mundler
authors.forename: Mathieu
authors.initials: M
authors.lastname: Ceccaldi
authors.forename: Eric
authors.initials: E
authors.lastname: Guedj
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D053858:Metabolic Networks and Pathways / Q000502:physiology; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D053327:Apolipoprotein E4; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18