The effect of amyloid pathology and glucose metabolism on cortical volume loss over time in Alzheimer’s disease

  • Sofie M. AdriaanseEmail author
  • Koene R. A. van Dijk
  • Rik Ossenkoppele
  • Martin Reuter
  • Nelleke Tolboom
  • Marissa D. Zwan
  • Maqsood Yaqub
  • Ronald Boellaard
  • Albert D. Windhorst
  • Wiesje M. van der Flier
  • Philip Scheltens
  • Adriaan A. Lammertsma
  • Frederik Barkhof
  • Bart N. M. van Berckel
Original Article



The present multimodal neuroimaging study examined whether amyloid pathology and glucose metabolism are related to cortical volume loss over time in Alzheimer’s disease (AD) patients and healthy elderly controls.


Structural MRI scans of eleven AD patients and ten controls were available at baseline and follow-up (mean interval 2.5 years). Change in brain structure over time was defined as percent change of cortical volume within seven a-priori defined regions that typically show the strongest structural loss in AD. In addition, two PET scans were performed at baseline: [11C]PIB to assess amyloid-β plaque load and [18F]FDG to assess glucose metabolism. [11C]PIB binding and [18F]FDG uptake were measured in the precuneus, a region in which both amyloid deposition and glucose hypometabolism occur early in the course of AD.


While amyloid-β plaque load at baseline was not related to cortical volume loss over time in either group, glucose metabolism within the group of AD patients was significantly related to volume loss over time (rho = 0.56, p < 0.05).


The present study shows that in a group of AD patients amyloid-β plaque load as measured by [11C]PIB behaves as a trait marker (i.e., all AD patients showed elevated levels of amyloid, not related to subsequent disease course), whilst hypometabolism as measured by [18F]FDG changed over time indicating that it could serve as a state marker that is predictive of neurodegeneration.


Alzheimer’s disease Amyloid plaques Hypometabolism Atrophy Longitudinal study 



This study was sponsored by Internationale Stichting Alzheimer Onderzoek (ISAO; project number #11539) and Hersenstichting Nederland (KS2011(1)-24).

We thank the support of the Athinoula A. Martinos Center for Biomedical Imaging at MGH including analysis methods developed by NIH grant P41RR14075.

Disclosure statement

Dr. Van Berckel receives research support from the American Health Assistance Foundation, Alzheimer Association, Internationale Stichting Alzheimer Onderzoek, the Center of Translational Molecular Medicine and the Dutch Organisation for Scientific Research.

Dr. Barkhof serves on the editorial boards of Brain, European Radiology, the Journal of Neurology, Neurosurgery & Psychiatry, the Journal of Neurology, Multiple Sclerosis and Neuroradiology and serves as a consultant for Bayer-Schering Pharma, Sanofi-Aventis, Biogen-Idec, UCB, Merck-Serono, Jansen Alzheimer Immunotherapy, Baxter, Novartis and Roche.

Dr. Scheltens serves/has served on the advisory boards of: Genentech, Novartis, Roche, Danone, Nutricia, Baxter and Lundbeck. He has been a speaker at symposia organised by Lundbeck, Merz, Danone, Novartis, Roche and Genentech. For all his activities he receives no personal compensation. He serves on the editorial board of Alzheimer’s Research & Therapy and Alzheimer Disease and Associated Disorders, is a member of the scientific advisory board of the EU Joint Programming Initiative and the French National Plan Alzheimer.

Dr. Reuter receives funding from several grants: NINDS 5R01NS052585-05, NIBIB 5R01EB006758-04, NINDS 2-R01-NS042861-06A1, NINDS 5-P01-NS058793-03, and NICHD R01-HD071664.

There are no other actual or potential conflicts of interest to disclose. All authors have read and agreed with the contents of the manuscript. The results of the study have not been published before and they are not under consideration to be published by another journal.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Sofie M. Adriaanse
    • 1
    • 8
    Email author
  • Koene R. A. van Dijk
    • 2
    • 5
  • Rik Ossenkoppele
    • 3
  • Martin Reuter
    • 5
    • 6
  • Nelleke Tolboom
    • 3
  • Marissa D. Zwan
    • 3
  • Maqsood Yaqub
    • 4
  • Ronald Boellaard
    • 4
  • Albert D. Windhorst
    • 4
  • Wiesje M. van der Flier
    • 7
  • Philip Scheltens
    • 7
  • Adriaan A. Lammertsma
    • 4
  • Frederik Barkhof
    • 3
  • Bart N. M. van Berckel
    • 3
  1. 1.Department of Radiology and Nuclear MedicineVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Department of Psychology, Center for Brain ScienceHarvard UniversityCambridgeUSA
  3. 3.Department of Radiology and Nuclear Medicine, Alzheimer Center, Neuroscience Campus AmsterdamVU University Medical CenterAmsterdamThe Netherlands
  4. 4.Department of Radiology and Nuclear Medicine, Neuroscience Campus AmsterdamVU University Medical CenterAmsterdamThe Netherlands
  5. 5.Athinoula A. Martinos Center for Biomedical ImagingMassachusetts General HospitalCharlestownUSA
  6. 6.Computer Science and Artificial Intelligence Laboratory, Division of Health Sciences and TechnologyMassachusetts Institute of TechnologyCambridgeUSA
  7. 7.Department of Neurology, Alzheimer Center, Neuroscience Campus AmsterdamVU University Medical CenterAmsterdamThe Netherlands
  8. 8.Department of Radiology and Nuclear Medicine, Alzheimer Center, Neuroscience Campus AmsterdamVU University Medical CenterAmsterdamThe Netherlands

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