title: Dissociation between brain amyloid deposition and metabolism in early mild cognitive impairment.
abstract: BACKGROUND
  The hypothetical model of dynamic biomarkers for Alzheimer's disease (AD) describes high amyloid deposition and hypometabolism at the mild cognitive impairment (MCI) stage. However, it remains unknown whether brain amyloidosis and hypometabolism follow the same trajectories in MCI individuals. We used the concept of early MCI (EMCI) and late MCI (LMCI) as defined by the Alzheimer's disease Neuroimaging Initiative (ADNI)-Go in order to compare the biomarker profile between EMCI and LMCI.
  
  
  OBJECTIVE
  To examine the global and voxel-based neocortical amyloid burden and metabolism among individuals who are cognitively normal (CN), as well as those with EMCI, LMCI and mild AD.
  
  
  METHODS
  In the present study, 354 participants, including CN (n = 109), EMCI (n = 157), LMCI (n = 39) and AD (n = 49), were enrolled between September 2009 and November 2011 through ADNI-GO and ADNI-2. Brain amyloid load and metabolism were estimated using [(18)F]AV45 and [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET, respectively. Uptake ratio images of [(18)F]AV45 and [(18)F]FDG were calculated by dividing the summed PET image by the median counts of the grey matter of the cerebellum and pons, respectively. Group differences of global [(18)F]AV45 and [(18)F]FDG were analyzed using ANOVA, while the voxel-based group differences were estimated using statistic parametric mapping (SPM).
  
  
  RESULTS
  EMCI patients showed higher global [(18)F]AV45 retention compared to CN and lower uptake compared to LMCI. SPM detected higher [(18)F]AV45 uptake in EMCI compared to CN in the precuneus, posterior cingulate, medial and dorsal lateral prefrontal cortices, bilaterally. EMCI showed lower [(18)F]AV45 retention than LMCI in the superior temporal, inferior parietal, as well as dorsal lateral prefrontal cortices, bilaterally. Regarding to the global [(18)F]FDG, EMCI patients showed no significant difference from CN and a higher uptake ratio compared to LMCI. At the voxel level, EMCI showed higher metabolism in precuneus, hippocampus, entorhinal and inferior parietal cortices, as compared to LMCI.
  
  
  CONCLUSIONS
  The present results indicate that brain metabolism remains normal despite the presence of significant amyloid accumulation in EMCI. These results suggest a role for anti-amyloid interventions in EMCI aiming to delay or halt the deposition of amyloid and related metabolism impairment.
authors.affiliation: Translational Neuroimaging Laboratory, Douglas Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Liyong
authors.initials: L
authors.lastname: Wu
authors.forename: Jared
authors.initials: J
authors.lastname: Rowley
authors.forename: Sara
authors.initials: S
authors.lastname: Mohades
authors.forename: Antoine
authors.initials: A
authors.lastname: Leuzy
authors.forename: Marina Tedeschi
authors.initials: MT
authors.lastname: Dauar
authors.forename: Monica
authors.initials: M
authors.lastname: Shin
authors.forename: Vladimir
authors.initials: V
authors.lastname: Fonov
authors.forename: Jianping
authors.initials: J
authors.lastname: Jia
authors.forename: Serge
authors.initials: S
authors.lastname: Gauthier
authors.forename: Pedro
authors.initials: P
authors.lastname: Rosa-Neto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography
chemical_list: D000682:Amyloid; D019788:Fluorodeoxyglucose F18