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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-02-2014 | Original Article

Five-year follow-up of ¹¹C-PIB uptake in Alzheimer’s disease and MCI

Authors: N. M. Kemppainen, N. M. Scheinin, J. Koivunen, J. Johansson, J. T. Toivonen, K. Någren, J. Rokka, M. Karrasch, R. Parkkola, J. O. Rinne

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2014

Abstract

Purpose

The aim of this study was to evaluate the longitudinal changes in [¹¹C]PIB uptake in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) over a long-term follow-up.

Methods

Six AD patients, ten MCI patients and eight healthy subjects underwent a [¹¹C]PIB PET scan at baseline and at 2 and 5 years. The clinical status of the MCI patients was evaluated every 6 months.

Results

The MCI group showed a significant increase in [¹¹C]PIB uptake over time (p < 0.001), with a similar increase from baseline to 2 years (4.7 % per year) and from 2 to 5 years (5.0 % per year). Eight MCI patients (80 %) converted to AD, and two of these patients showed a normal [¹¹C]PIB scan at baseline but increased uptake later. There was an increase in [¹¹C]PIB uptake with time in the AD group (p = 0.02), but this did not significantly differ from the change in the control group.

Conclusion

Our results revealed a significant increase in amyloid load even at the time of AD diagnosis in some of the MCI patients who converted. A positive [¹¹C]PIB scan at baseline in MCI patients strongly predicted future conversion to AD but a negative PIB scan in MCI patients did not exclude future conversion. The results suggest that there is wide individual variation in the brain amyloid load in MCI, and in the course of amyloid accumulation in relation to the clinical diagnosis of AD.

Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science. 2002;297(5580):353–6.PubMedCrossRef

Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol. 2004;55(3):306–19.PubMedCrossRef

Kemppainen NM, Aalto S, Wilson IA, Nagren K, Helin S, Bruck A, et al. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology. 2007;68(19):1603–6.PubMedCrossRef

Engler H, Forsberg A, Almkvist O, Blomquist G, Larsson E, Savitcheva I, et al. Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain. 2006;129(Pt 11):2856–66.PubMedCrossRef

Jack Jr CR, Lowe VJ, Weigand SD, Wiste HJ, Senjem ML, Knopman DS, et al. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: implications for sequence of pathological events in Alzheimer’s disease. Brain. 2009;132(Pt 5):1355–65.PubMedCrossRef

Ossenkoppele R, Tolboom N, Foster-Dingley JC, Adriaanse SF, Boellaard R, Yaqub M, et al. Longitudinal imaging of Alzheimer pathology using [11C]PIB, [18F]FDDNP and [18F]FDG PET. Eur J Nucl Med Mol Imaging. 2012;39(6):990–1000.PubMedCrossRef

Scheinin NM, Aalto S, Koikkalainen J, Lotjonen J, Karrasch M, Kemppainen N, et al. Follow-up of [11C]PIB uptake and brain volume in patients with Alzheimer disease and controls. Neurology. 2009;73(15):1186–92.PubMedCrossRef

Grimmer T, Tholen S, Yousefi BH, Alexopoulos P, Forschler A, Forstl H, et al. Progression of cerebral amyloid load is associated with the apolipoprotein E epsilon4 genotype in Alzheimer’s disease. Biol Psychiatry. 2010;68(10):879–84.PubMedCentralPubMedCrossRef

Rinne JO, Brooks DJ, Rossor MN, Fox NC, Bullock R, Klunk WE, et al. 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer’s disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol. 2010;9(4):363–72.PubMedCrossRef

10.

Villemagne VL, Pike KE, Chetelat G, Ellis KA, Mulligan RS, Bourgeat P, et al. Longitudinal assessment of Abeta and cognition in aging and Alzheimer disease. Ann Neurol. 2011;69(1):181–92.PubMedCentralPubMedCrossRef

11.

Kadir A, Almkvist O, Forsberg A, Wall A, Engler H, Langstrom B, et al. Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer’s disease. Neurobiol Aging. 2012;33(1):198.e1–14.CrossRef

12.

Koivunen J, Scheinin N, Virta JR, Aalto S, Vahlberg T, Nagren K, et al. Amyloid PET imaging in patients with mild cognitive impairment: a 2-year follow-up study. Neurology. 2011;76(12):1085–90.PubMedCrossRef

13.

Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol. 2013;12(4):357–67.PubMedCrossRef

14.

Forsberg A, Engler H, Almkvist O, Blomquist G, Hagman G, Wall A, et al. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging. 2008;29(10):1456–65.PubMedCrossRef

15.

Okello A, Koivunen J, Edison P, Archer HA, Turkheimer FE, Nagren K, et al. Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study. Neurology. 2009;73(10):754–60.PubMedCrossRef

16.

Zhang S, Han D, Tan X, Feng J, Guo Y, Ding Y. Diagnostic accuracy of 18F-FDG and 11C-PIB-PET for prediction of short-term conversion to Alzheimer’s disease in subjects with mild cognitive impairment. Int J Clin Pract. 2012;66(2):185–98.PubMedCrossRef

17.

Kemppainen NM, Aalto S, Wilson IA, Nagren K, Helin S, Bruck A, et al. Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. Neurology. 2006;67(9):1575–80.PubMedCrossRef

18.

Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review. Report of the quality standards subcommittee of the American Academy of Neurology). Neurology. 2001;56(9):1133–42.PubMedCrossRef

19.

Ashburner J, Friston KJ. Unified segmentation. Neuroimage. 2005;26(3):839–51.PubMedCrossRef

20.

Aalto S, Scheinin NM, Kemppainen NM, Nagren K, Kailajarvi M, Leinonen M, et al. Reproducibility of automated simplified voxel-based analysis of PET amyloid ligand [11C]PIB uptake using 30-min scanning data. Eur J Nucl Med Mol Imaging. 2009;36(10):1651–60.PubMedCrossRef

21.

Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010;31(8):1275–83.PubMedCrossRef

22.

Jack Jr CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9(1):119–28.PubMedCentralPubMedCrossRef

23.

Knopman DS, DeKosky ST, Cummings JL, Chui H, Corey-Bloom J, Relkin N, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the quality standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56(9):1143–53.PubMedCrossRef

24.

Kemppainen NM, Aalto S, Karrasch M, Nagren K, Savisto N, Oikonen V, et al. Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer’s disease. Ann Neurol. 2008;63(1):112–8.PubMedCrossRef

25.

Ikonomovic MD, Abrahamson EE, Price JC, Hamilton RL, Mathis CA, Paljug WR, et al. Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study. Acta Neuropathol. 2012;123(3):433–47.PubMedCentralPubMedCrossRef

26.

Driscoll I, Troncoso JC, Rudow G, Sojkova J, Pletnikova O, Zhou Y, et al. Correspondence between in vivo (11)C-PiB-PET amyloid imaging and postmortem, region-matched assessment of plaques. Acta Neuropathol. 2012;124(6):823–31.PubMedCentralPubMedCrossRef

27.

Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68(20):1718–25.PubMedCrossRef

28.

Nordberg A, Carter SF, Rinne J, Drzezga A, Brooks DJ, Vandenberghe R, et al. A European multicentre PET study of fibrillar amyloid in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2013;40(1):104–14.PubMedCentralPubMedCrossRef

Title: Five-year follow-up of 11C-PIB uptake in Alzheimer’s disease and MCI
Authors: N. M. Kemppainen
N. M. Scheinin
J. Koivunen
J. Johansson
J. T. Toivonen
K. Någren
J. Rokka
M. Karrasch
R. Parkkola
J. O. Rinne
Publication date: 01-02-2014
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2014
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-013-2562-0

At a glance: The STEP trials

Springer Medicine

Five-year follow-up of ¹¹C-PIB uptake in Alzheimer’s disease and MCI

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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