title: Evaluation of a calibrated (18)F-FDG PET score as a biomarker for progression in Alzheimer disease and mild cognitive impairment.
abstract: Increasingly, clinical trials are being planned in patients with mild cognitive impairment (MCI) to prevent or delay the onset of dementia in Alzheimer disease (AD) by disease-modifying intervention. Inclusion of imaging techniques as biomarkers for patient selection and assessment of outcome is expected to increase trial efficacy. PET using (18)F-FDG provides objective information about the impairment of synaptic function and could, with appropriate standardization, qualify as a biomarker.
  
  
  METHODS
  We evaluated a predefined quantitative measure (PET score) that is extracted automatically from (18)F-FDG PET scans using a sample of controls (n = 44), patients with MCI (n = 94), and patients with mild AD (n = 40) from the Alzheimer Disease Neuroimaging Initiative (ADNI). Subjects received 4 scans and clinical assessments over 2 y.
  
  
  RESULTS
  PET scores provide much higher test-retest reliability than standard neuropsychologic test scores (Alzheimer's Disease Assessment Scale-Cognitive [ADAS-cog] and Mini-Mental State Examination) and superior signal strength for measuring progression. At the same time, they are related linearly to ADAS-cog scores, thus providing a valid measure of cognitive impairment. In addition, PET scores at study entry in MCI patients significantly predict clinical progression to dementia with a higher accuracy than Mini-Mental State Examination and ADAS-cog.
  
  
  CONCLUSIONS
  (18)F-FDG PET scores are a valid imaging biomarker to monitor the progression of MCI to AD. Their superior test-retest reliability and signal strength will allow the reduction in the number of subjects needed or shortening of study duration substantially.
authors.affiliation: Wolfson Molecular Imaging Centre, School of Cancer and Enabling Sciences, University of Manchester, Manchester, UK. karl.herholz@manchester.ac.uk
authors.forename: Karl
authors.initials: K
authors.lastname: Herholz
authors.forename: Sarah
authors.initials: S
authors.lastname: Westwood
authors.forename: Cathleen
authors.initials: C
authors.lastname: Haense
authors.forename: Graham
authors.initials: G
authors.lastname: Dunn
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002138:Calibration; D003071:Cognition; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009462:Neurology / Q000379:methods; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D019788:Fluorodeoxyglucose F18