Skip to main content

Advertisement

Log in

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

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. 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.

    Article  CAS  PubMed  Google Scholar 

  2. 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.

    Article  CAS  PubMed  Google Scholar 

  3. 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.

    Article  CAS  PubMed  Google Scholar 

  4. 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.

    Article  PubMed  Google Scholar 

  5. 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.

    Article  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This study was financially supported by EVO grants from Turku University Hospital, the Sigrid Juselius Foundation and the Research Council for Health of the Academy of Finland (no. 15762). The authors thank the staff of the Turku PET Centre for technical assistance.

Conflicts of interest

This was an academic work and did not receive support from the medical industry or other companies. Dr. Kemppainen has received research support from the Finnish Medical Society Duodecim, the Finnish Cultural Foundation and the Orion-Farmos Research Foundation. Dr. Scheinin has received research support from the Orion-Farmos Research Foundation. Dr. Parkkola has received EVO grants from Turku University Hospital (year 2012). Dr. Rinne has received clinical grants from Turku University Hospital (EVO), Sigrid Juselius Foundation and Academy of Finland. Drs. Koivunen, Johansson, Toivonen, Någren, Rokka, and Karrasch report no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N. M. Kemppainen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kemppainen, N.M., Scheinin, N.M., Koivunen, J. et al. Five-year follow-up of 11C-PIB uptake in Alzheimer’s disease and MCI. Eur J Nucl Med Mol Imaging 41, 283–289 (2014). https://doi.org/10.1007/s00259-013-2562-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-013-2562-0

Keywords

Navigation