Brain Advance Access originally published online on July 19, 2006
Brain 2006 129(11):2856-2866; doi:10.1093/brain/awl178
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Two-year follow-up of amyloid deposition in patients with Alzheimer's disease
1 Uppsala Imanet AB, Imanet, GE Healthcare Uppsala University, Uppsala 2 Uppsala University Hospital Uppsala University, Uppsala 3 Department of Oncology, Radiology and Clinical Immunology Uppsala University, Uppsala 4 Department of Biochemistry and Organic Chemistry Uppsala University, Uppsala 5 Division of Molecular Neuropharmacology, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet Stockholm, Sweden 6 Department of Geriatric Medicine, Karolinska University Hospital Huddinge Stockholm, Sweden 7 Department of Psychology, Stockholm University Stockholm, Sweden
Correspondence to: Prof. Agneta Nordberg, MD, PhD, Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Molecular Neuropharmacology, Karolinska University Hospital Huddinge, Novum, S-141 86 Stockholm, Sweden E-mail: Agneta.K.Nordberg{at}ki.se
Beta amyloid is one of the major histopathological hallmarks of Alzheimer's disease. We recently reported in vivo imaging of amyloid in 16 Alzheimer patients, using the PET ligand N-methyl[11C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole (PIB). In the present study we rescanned these 16 Alzheimer patients after 2.0 ± 0.5 years and have described the interval change in amyloid deposition and regional cerebral metabolic rate for glucose (rCMRGlc) at follow-up. Sixteen patients with Alzheimer's disease were re-examined by means of PET, using PIB and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) after 2.0 ± 0.5 years. The patients were all on cholinesterase inhibitor treatment and five also on treatment with the N-methyl-D-aspartate (NMDA) antagonist memantine. In order to estimate the accuracy of the PET PIB measurements, four additional Alzheimer patients underwent repeated examinations with PIB within 20 days (test–retest). Relative PIB retention in cortical regions differed by 3–7% in the test–retest study. No significant difference in PIB retention was observed between baseline and follow-up while a significant (P < 0.01) 20% decrease in rCMRGlc was observed in cortical brain regions. A significant negative correlation between rCMRGlc and PIB retention was observed in the parietal cortex in the Alzheimer patients at follow-up (r = 0.67, P = 0.009). A non-significant decline in Mini-Mental State Examination (MMSE) score from 24.3 ± 3.7 (mean ± standard deviation) to 22.7 ± 6.1 was measured at follow-up. Five of the Alzheimer patients showed a significant decline in MMSE score of >3 (21.4 ± 3.5 to 15.6 ± 3.9, P < 0.01) (AD-progressive) while the rest of the patients were cognitively more stable (MMSE score = 25.6 ± 3.1 to 25.9 ± 3.7) (AD-stable) compared with baseline. A positive correlation (P = 0.001) was observed in the parietal cortex between Rey Auditory Verbal Learning (RAVL) test score and rCMRGlc at follow-up while a negative correlation (P = 0.018) was observed between RAVL test and PIB retention in the parietal at follow-up. Relatively stable PIB retention after 2 years of follow-up in patients with mild Alzheimer's disease suggests that amyloid deposition in the brain reaches a plateau by the early clinical stages of Alzheimer's disease and therefore may precede a decline in rCMRGlc and cognition. It appears that anti-amyloid therapies will need to induce a significant decrease in amyloid load in order for PIB PET images to detect a drug effect in Alzheimer patients. FDG imaging may be able to detect a stabilization of cerebral metabolism caused by therapy administered to patients with a clinical diagnosis of Alzheimer's disease.
Key Words: Alzheimer's disease; amyloid; PET; PIB; FDG; follow-up
Abbreviations: BBB, brain–blood barrier; CBF, cerebral blood flow; FDG, 2-[18F]fluoro-2-deoxy-D-glucose; HC, healthy controls; MMSE, Mini-Mental State Examination; OHC, oldest healthy control; PIB, N-methyl[11C]2-(4' methylaminophenyl)-6-hydroxy-benzothiazole; rCMRGlc, regional cerebral metabolic rate for glucose; RAVL, Rey Auditory Verbal Learning; ROIs, regions of interest; SD, standard deviation
Received March 18, 2006. Revised May 26, 2006. Accepted June 7, 2006.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease Brain, March 12, 2008; (2008) awn016v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Jack Jr, V. J. Lowe, M. L. Senjem, S. D. Weigand, B. J. Kemp, M. M. Shiung, D. S. Knopman, B. F. Boeve, W. E. Klunk, C. A. Mathis, et al. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment Brain, March 1, 2008; 131(3): 665 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chetelat, B. Desgranges, B. Landeau, F. Mezenge, J. B. Poline, V. de la Sayette, F. Viader, F. Eustache, and J.-C. Baron Direct voxel-based comparison between grey matter hypometabolism and atrophy in Alzheimer's disease Brain, January 1, 2008; 131(1): 60 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J T O'BRIEN Role of imaging techniques in the diagnosis of dementia Br. J. Radiol., December 1, 2007; 80(Special_Issue_2): S71 - S77. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R I SCAHILL and N C FOX Longitudinal imaging in dementia Br. J. Radiol., December 1, 2007; 80(Special_Issue_2): S92 - S98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K HERHOLZ, S F CARTER, and M JONES Positron emission tomography imaging in dementia Br. J. Radiol., December 1, 2007; 80(Special_Issue_2): S160 - S167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Pike, G. Savage, V. L. Villemagne, S. Ng, S. A. Moss, P. Maruff, C. A. Mathis, W. E. Klunk, C. L. Masters, and C. C. Rowe {beta}-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease Brain, November 1, 2007; 130(11): 2837 - 2844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Maeda, B. Ji, T. Irie, T. Tomiyama, M. Maruyama, T. Okauchi, M. Staufenbiel, N. Iwata, M. Ono, T. C. Saido, et al. Longitudinal, Quantitative Assessment of Amyloid, Neuroinflammation, and Anti-Amyloid Treatment in a Living Mouse Model of Alzheimer's Disease Enabled by Positron Emission Tomography J. Neurosci., October 10, 2007; 27(41): 10957 - 10968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Alladi, J. Xuereb, T. Bak, P. Nestor, J. Knibb, K. Patterson, and J. R. Hodges Focal cortical presentations of Alzheimer's disease Brain, October 1, 2007; 130(10): 2636 - 2645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Goldstein, Y. Cao, T. Fiedler, J. Toyn, L. Iben, D. M. Barten, M. Pierdomenico, J. Corsa, C. V. C. Prasad, R. E. Olson, et al. Ex Vivo Occupancy of {gamma}-Secretase Inhibitors Correlates with Brain beta-Amyloid Peptide Reduction in Tg2576 Mice J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 102 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lockhart, J.R. Lamb, T. Osredkar, L.I. Sue, J.N. Joyce, L. Ye, V. Libri, D. Leppert, and T.G. Beach PIB is a non-specific imaging marker of amyloid-beta (A{beta}) peptide-related cerebral amyloidosis Brain, October 1, 2007; 130(10): 2607 - 2615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nelissen, M. Vandenbulcke, K. Fannes, A. Verbruggen, R. Peeters, P. Dupont, K. Van Laere, G. Bormans, and R. Vandenberghe A{beta} amyloid deposition in the language system and how the brain responds Brain, August 1, 2007; 130(8): 2055 - 2069. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Rowe, S. Ng, U. Ackermann, S. J. Gong, K. Pike, G. Savage, T. F. Cowie, K. L. Dickinson, P. Maruff, D. Darby, et al. Imaging {beta}-amyloid burden in aging and dementia Neurology, May 15, 2007; 68(20): 1718 - 1725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Rabinovici, A. J. Furst, J. P. O'Neil, C. A. Racine, E. C. Mormino, S. L. Baker, S. Chetty, P. Patel, T. A. Pagliaro, W. E. Klunk, et al. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration Neurology, April 10, 2007; 68(15): 1205 - 1212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M REIMAN Linking Brain Imaging and Genomics in the Study of Alzheimer's Disease and Aging Ann. N.Y. Acad. Sci., February 1, 2007; 1097(1): 94 - 113. [Abstract] [Full Text] [PDF]
|
|