title: Amyloid deposition, hypometabolism, and longitudinal cognitive decline.
abstract: OBJECTIVE
  Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) population, we examined (1) cross-sectional relationships between amyloid deposition, hypometabolism, and cognition, and (2) associations between amyloid and hypometabolism measurements and longitudinal cognitive measurements.
  
  
  METHODS
  We examined associations between mean cortical florbetapir uptake, mean (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) within a set of predefined regions, and Alzhiemer's Disease Assessment Scale (ADAS-cog) performance in 426 ADNI participants (126 normal, 162 early mild cognitive impairment [EMCI], 85 late MCI [LMCI], 53 Alzheimer disease [AD] patients). For a subset of these (76 normal, 81 LMCI) we determined whether florbetapir and FDG-PET were associated with retrospective decline in longitudinal ADAS-cog measurements.
  
  
  RESULTS
  Twenty-nine percent of normal subjects, 43% of EMCI patients, 62% of LMCI patients, and 77% of AD patients were categorized as florbetapir positive. Florbetapir was negatively associated with concurrent FDG and ADAS-cog in both MCI groups. In longitudinal analyses, florbetapir-positive subjects in both normal and LMCI groups had greater ongoing ADAS-cog decline than those who were florbetapir negative. However, in normal subjects, florbetapir positivity was associated with greater ADAS-cog decline than FDG, whereas in LMCI, FDG positivity was associated with greater decline than florbetapir.
  
  
  CONCLUSIONS
  Although both hypometabolism and β-amyloid (Aβ) deposition are detectable in normal subjects and all diagnostic groups, Aβ showed greater associations with cognitive decline in normal participants. In view of the minimal cognitive deterioration overall in this group, this suggests that amyloid deposition has an early and subclinical impact on cognition that precedes metabolic changes. At moderate and later stages of disease (LMCI/AD), hypometabolism becomes more pronounced and more closely linked to ongoing cognitive decline.
authors.affiliation: Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, CA 94720-3190, USA. slandau@berkeley.edu
authors.forename: Susan M
authors.initials: SM
authors.lastname: Landau
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mintun
authors.forename: Abhinay D
authors.initials: AD
authors.lastname: Joshi
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
mesh_terms: D000368:Aged; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds; D001822:Body Burden; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology*; D060825:Cognitive Dysfunction / Q000473:pathology / Q000523:psychology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005026:Ethylene Glycols; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography
chemical_list: D000682:Amyloid; D000814:Aniline Compounds; D005026:Ethylene Glycols; D019788:Fluorodeoxyglucose F18; C545186:florbetapir