Skip to main content
SpringerLink
Log in

Translation of imaging biomarkers from clinical research to healthcare

Translation bildgebender Biomarker von klinischen Studien bis zur Gesundheitsversorgung

  • Beiträge zum Themenschwerpunkt
  • Published:
Zeitschrift für Gerontologie und Geriatrie Aims and scope Submit manuscript

Abstract

The use of biomarkers for diagnostics of Alzheimer’s disease (AD) has increased over the last years in specialized care and experimental settings. With the possibly upcoming availability of disease-modifying therapeutic agents, the diagnostics and treatment of patients with cognitive impairment will change. Biomarkers will be used as theranostic markers for case finding. The development and evaluation of biomarkers can be framed in a phase model from preclinical studies through trials in expert center settings to the evaluation of biomarkers in primary care, up to testing the efficacy and the impact of biomarkers on the healthcare system. Hippocampal volumetry is the most accepted and in-depth tested biomarker for AD diagnostics and prediction of the course. Therefore, hippocampus volumetry is used to illustrate the phase model of biomarker development and present the milestones already achieved and questions still to be resolved.

Zusammenfassung

Die Diagnostik der Alzheimer-Krankheit an spezialisierten Zentren hat sich bereits durch die vermehrte Nutzung von Biomarkern verändert. Eine eventuell in den nächsten Jahren bevorstehende Zulassung von krankheitsmodifizierenden Medikamenten zur Behandlung der Alzheimer Krankheit wird den Ablauf der Regeldiagnostik beeinflussen. Biomarker werden dann als wichtiges Theranostikum benötigt. Ein Phasenmodell beschreibt die Entwicklung und Erprobung von Biomarkern von der präklinischen Suche nach möglichen Zielmarkern über wissenschaftliche Untersuchungen in experimentellen Stichproben bis hin zur Erprobung der Effektivität eines Biomarkers in der Primärversorgung. Der bisher am umfangreichsten untersuchte Biomarker zur Diagnostik und Prädiktion des Verlaufs einer Alzheimer-Krankheit ist das Volumen des Hippokampus. Anhand der Hippokampusvolumetrie werden die bereits erreichten Meilensteine aufgezeigt und die noch offenen Fragen bei der Entwicklung von Biomarkern für die Alzheimer-Krankheit dargestellt.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Albert MS, Dekosky ST, Dickson D et al (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:270–279

    Article  PubMed  PubMed Central  Google Scholar 

  2. Anonymous (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95

    Article  Google Scholar 

  3. Ball MJ (1977) Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A quantitative study. Acta Neuropathol 37:111–118

    Article  CAS  PubMed  Google Scholar 

  4. Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95

    Article  Google Scholar 

  5. Bobinski M, De Leon MJ, Wegiel J et al (2000) The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer’s disease. Neuroscience 95:721–725

    Article  CAS  PubMed  Google Scholar 

  6. Boccardi M, Ganzola R, Bocchetta M et al (2011) Survey of protocols for the manual segmentation of the hippocampus: preparatory steps towards a joint EADC-ADNI harmonized protocol. J Alzheimers Dis 26(Suppl 3):61–75

    PubMed  Google Scholar 

  7. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259

    Article  CAS  PubMed  Google Scholar 

  8. Brueggen K, Dyrba M, Barkhof F et al (2015) Basal forebrain and hippocampus as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment – A multicenter DTI and volumetry study. J Alzheimers Dis 48:197–204

    Article  PubMed  Google Scholar 

  9. Clerx L, Van Rossum IA, Burns L et al (2013) Measurements of medial temporal lobe atrophy for prediction of Alzheimer’s disease in subjects with mild cognitive impairment. Neurobiol Aging 34:2003–2013

    Article  PubMed  Google Scholar 

  10. De Leon MJ, George AE, Stylopoulos LA et al (1989) Early marker for Alzheimer’s disease: the atrophic hippocampus. Lancet 2:672–673

    Article  PubMed  Google Scholar 

  11. De Leon MJ, Golomb J, George AE et al (1993) The radiologic prediction of Alzheimer disease: the atrophic hippocampal formation. AJNR Am J Neuroradiol 14:897–906

    PubMed  Google Scholar 

  12. Frisoni GB, Jack CR Jr., Bocchetta M et al (2015) The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: evidence of validity. Alzheimers Dement 11:111–125

    Article  PubMed  Google Scholar 

  13. Galluzzi S, Geroldi C, Ghidoni R et al (2010) The new Alzheimer’s criteria in a naturalistic series of patients with mild cognitive impairment. J Neurol 257:2004–2014

    Article  CAS  PubMed  Google Scholar 

  14. Gosche KM, Mortimer JA, Smith CD et al (2002) Hippocampal volume as an index of Alzheimer neuropathology: findings from the Nun Study. Neurology 58:1476–1482

    Article  CAS  PubMed  Google Scholar 

  15. Hampel H, Prvulovic D, Teipel S et al (2011) The future of Alzheimer’s disease: the next 10 years. Prog Neurobiol 95:718–728

    Article  PubMed  Google Scholar 

  16. Jack CR Jr., Dickson DW, Parisi JE et al (2002) Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia. Neurology 58:750–757

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kesslak JP, Nalcioglu O, Cotman CW (1991) Quantification of magnetic resonance scans for hippocampal and parahippocampal atrophy in Alzheimer’s disease. Neurology 41:51–54

    Article  CAS  PubMed  Google Scholar 

  18. Mckhann GM, Knopman DS, Chertkow H et al (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:263–269

    Article  PubMed  PubMed Central  Google Scholar 

  19. Panza F, Seripa D, Solfrizzi V et al (2016) Emerging drugs to reduce abnormal beta-amyloid protein in Alzheimer’s disease patients. Expert Opin Emerg Drugs. doi:10.1080/14728214.2016.1241232

    PubMed  Google Scholar 

  20. Pepe MS, Cai T, Longton G (2006) Combining predictors for classification using the area under the receiver operating characteristic curve. Biometrics 62:221–229

    Article  PubMed  Google Scholar 

  21. Pepe MS, Etzioni R, Feng Z et al (2001) Phases of biomarker development for early detection of cancer. J Natl Cancer Inst 93:1054–1061

    Article  CAS  PubMed  Google Scholar 

  22. Risacher SL, Saykin AJ, West JD et al (2009) Baseline MRI predictors of conversion from MCI to probable AD in the ADNI cohort. Curr Alzheimer Res 6:347–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schuff N, Woerner N, Boreta L et al (2009) MRI of hippocampal volume loss in early Alzheimer’s disease in relation to ApoE genotype and biomarkers. Brain 132:1067–1077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Teipel S, Drzezga A, Grothe MJ et al (2015) Multimodal imaging in Alzheimer’s disease: validity and usefulness for early detection. Lancet Neurol 14:1037–1053

    Article  PubMed  Google Scholar 

  25. Teipel SJ, Keller F, Thyrian JR et al (2017) Hippocampus and basal forebrain volumetry for dementia and mild cognitive impairment diagnosis: could it be useful in primary care? J Alzheimers Dis 55:1379–1394

    Article  PubMed  Google Scholar 

  26. Thyrian JR, Fiss T, Dreier A et al (2012) Life- and person-centred help in Mecklenburg-Western Pomerania, Germany (DelpHi): study protocol for a randomised controlled trial. Trials 13:56

    Article  PubMed  PubMed Central  Google Scholar 

  27. Varon D, Barker W, Loewenstein D et al (2015) Visual rating and volumetric measurement of medial temporal atrophy in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort: baseline diagnosis and the prediction of MCI outcome. Int J Geriatr Psychiatry 30:192–200

    Article  PubMed  Google Scholar 

  28. Wolf D, Bocchetta M, Preboske GM et al (2017) Reference standard space hippocampus labels according to the EADC-ADNI harmonized protocol: Utility in automated volumetry. Alzheimers Dement. doi:10.1016/j.jalz.2017.01.009

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. German Center for Neurodegenerative Disease (DZNE) Rostock/Greifswald, Gehlsdorfer Str. 20, 18147, Rostock, Germany

    Ingo Kilimann, Jochen René Thyrian & Stefan J. Teipel

  2. University Hospital Rostock, University Rostock, Rostock, Germany

    Ingo Kilimann & Stefan J. Teipel

  3. Institute for Community Medicine, University Hospital Greifswald, Greifswald, Germany

    Wolfgang Hoffmann

  4. German Center for Neurodegenerative Disease (DZNE) Rostock/Greifswald, Ellerholtzstrasse 1, 17489, Greifswald, Germany

    Wolfgang Hoffmann

Authors
  1. Ingo Kilimann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jochen René Thyrian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wolfgang Hoffmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stefan J. Teipel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ingo Kilimann.

Ethics declarations

Conflict of interests

I. Kilimann, J.R. Thyrian, W. Hoffmann and S.J. Teipel declare that they have no competing interests.

This article does not contain any studies with human participants or animals performed by any of the authors.

The supplement containing this article is not sponsored by industry.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kilimann, I., Thyrian, J.R., Hoffmann, W. et al. Translation of imaging biomarkers from clinical research to healthcare. Z Gerontol Geriat 50 (Suppl 2), 84–88 (2017). https://doi.org/10.1007/s00391-017-1225-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00391-017-1225-3

Keywords

Schlüsselwörter

Search

Navigation