title: Regional expansion of hypometabolism in Alzheimer's disease follows amyloid deposition with temporal delay.
abstract: BACKGROUND
  Cross-sectional imaging studies suggest that patterns of hypometabolism (measured by [(18)F] fluorodeoxyglucose positron emission tomography [FDG-PET]) and amyloid deposition (measured by [(11)C] Pittsburgh Compound B [PiB]- PET) in Alzheimer's disease (AD) show some overlap with each other. This indicates that neuronal dysfunction might spread within the anatomical pattern of amyloid deposition. The aim of this study was to examine longitudinal regional patterns of amyloid deposition and hypometabolism in the same population of mild AD subjects and to establish their regional relationship to each other.
  
  
  METHODS
  Twenty patients with mild AD underwent baseline (BL) and follow-up (FU) examination with [(18)F] FDG-PET and [(11)C] PiB-PET. Voxel-by-voxel statistical group comparison (SPM5) was performed between patient BL- and FU-PET data as well as between patients and 15 PiB-negative elderly control subjects, who had undergone identical imaging procedures. To obtain objective measures of regional overlap, Dice similarity coefficients (DSC) between the imaging findings were calculated.
  
  
  RESULTS
  Compared with elderly control subjects, AD patients showed typical patterns of BL hypometabolism and BL amyloid deposition, with a similarity of 40% (DSC). Amyloid deposition was more extended than hypometabolism at BL and showed only minor changes over time, whereas significant expansion of hypometabolism was observed, almost exclusively within areas already affected by BL amyloid deposition. Thus, increased similarity of FU hypometabolism with BL amyloid deposition was found (DSC: 47%).
  
  
  CONCLUSIONS
  Longitudinal regional expansion of cerebral hypometabolism, as a measure of neuronal dysfunction in AD, seems to follow the anatomical pattern of amyloid deposition with temporal delay. This indicates that amyloid-based disruption of neuronal integrity might contribute to the regional expansion of neuronal dysfunction.
authors.affiliation: Department of Nuclear Medicine, Technische Universität München, Munich, Germany. stefan.foerster@lrz.tum.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Förster
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.forename: Isabelle
authors.initials: I
authors.lastname: Miederer
authors.forename: Gjermund
authors.initials: G
authors.lastname: Henriksen
authors.forename: Behrooz Hooshyar
authors.initials: BH
authors.lastname: Yousefi
authors.forename: Philipp
authors.initials: P
authors.lastname: Graner
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.forename: Hans
authors.initials: H
authors.lastname: Förstl
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
authors.forename: Bradford C
authors.initials: BC
authors.lastname: Dickerson
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D059907:Functional Neuroimaging / Q000379:methods / Q000523:psychology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods / Q000523:psychology; D019275:Radiopharmaceuticals; D013844:Thiazoles; D013997:Time Factors
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D015415:Biomarkers; D019275:Radiopharmaceuticals; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18