Brain Structure and Function

, Volume 214, Issue 4, pp 303–317 | Cite as

Cortical hypometabolism and hypoperfusion in Parkinson’s disease is extensive: probably even at early disease stages

  • Per Borghammer
  • Mallar Chakravarty
  • Kristjana Yr Jonsdottir
  • Noriko Sato
  • Hiroshi Matsuda
  • Kengo Ito
  • Yutaka Arahata
  • Takashi Kato
  • Albert Gjedde


Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson’s disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 early-stage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 late-stage PD patients with that of 13 controls. Three different normalization methods were compared: (1) GM normalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxel-based analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD.


Parkinson’s disease Normalization PET SPECT CBF Glucose 



The present study was supported by the Danish National Science Foundation (Dansk Grundforskningsfond), and Danish Parkinson’s Disease foundation (Dansk Parkinsonforening).

Conflict of interest statement


Supplementary material

Supplementary material 1 (TIFF 3577 kb)
Supplementary material 2 (TIFF 3577 kb)


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Per Borghammer
    • 1
    • 2
  • Mallar Chakravarty
    • 3
    • 4
    • 2
  • Kristjana Yr Jonsdottir
    • 3
  • Noriko Sato
    • 5
  • Hiroshi Matsuda
    • 6
  • Kengo Ito
    • 7
  • Yutaka Arahata
    • 7
  • Takashi Kato
    • 7
  • Albert Gjedde
    • 3
    • 2
  1. 1.Department of Nuclear MedicineAarhus University Hospitals, Aarhus Sygehus, NBGAarhusDenmark
  2. 2.PET CentreAarhus University Hospitals, Aarhus Sygehus, NBGAarhusDenmark
  3. 3.Center of Functionally Integrative NeuroscienceUniversity of AarhusAarhusDenmark
  4. 4.Allen Institute for Brain ScienceSeattleUSA
  5. 5.Department of RadiologyNational Center Hospital of Neurology and PsychiatryTokyoJapan
  6. 6.Department of Nuclear MedicineInternational Medical Center, Saitama Medical UniversitySaitamaJapan
  7. 7.Department of Brain Science and Molecular ImagingNational Center for Geriatrics and GerontologyObuJapan

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