title: Posterior cingulate glucose metabolism, hippocampal glucose metabolism, and hippocampal volume in cognitively normal, late-middle-aged persons at 3 levels of genetic risk for Alzheimer disease.
abstract: OBJECTIVE
  To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ε4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease.
  
  
  METHODS
  Cross-sectional comparison of measurements of cerebral glucose metabolism using 18F-fluorodeoxyglucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ε4 homozygotes, ε4 heterozygotes, and noncarriers.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  A total of 31 ε4 homozygotes, 42 ε4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level.
  
  
  METHODS
  The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume.
  
  
  RESULTS
  Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P = .60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P = .001). The APOE ε4 gene dose was significantly associated with posterior cingulate glucose metabolism (r = 0.29, P = .0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P < .05, determined by use of pairwise Fisher z tests).
  
  
  CONCLUSIONS
  Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or metabolism in cognitively normal persons at increased genetic risk for Alzheimer disease.
authors.affiliation: Banner Alzheimer's Institute, 901 E Willetta St, Phoenix, AZ 85006, USA. hillary.protas@bannerhealth.com
authors.forename: Hillary D
authors.initials: HD
authors.lastname: Protas
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.forename: Jessica B S
authors.initials: JB
authors.lastname: Langbaum
authors.forename: Adam S
authors.initials: AS
authors.lastname: Fleisher
authors.forename: Gene E
authors.initials: GE
authors.lastname: Alexander
authors.forename: Wendy
authors.initials: W
authors.lastname: Lee
authors.forename: Daniel
authors.initials: D
authors.lastname: Bandy
authors.forename: Mony J
authors.initials: MJ
authors.lastname: de Leon
authors.forename: Lisa
authors.initials: L
authors.lastname: Mosconi
authors.forename: Shannon
authors.initials: S
authors.lastname: Buckley
authors.forename: Diana
authors.initials: D
authors.lastname: Truran-Sacrey
authors.forename: Norbert
authors.initials: N
authors.lastname: Schuff
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Caselli
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009929:Organ Size; D012306:Risk
chemical_list: D005947:Glucose