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Structural integrity in subjective cognitive decline, mild cognitive impairment and Alzheimer’s disease based on multicenter diffusion tensor imaging

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Abstract

Introduction

Subjective cognitive decline (SCD) can represent a preclinical stage of Alzheimer’s disease. Diffusion tensor imaging (DTI) could aid an early diagnosis, yet only few monocentric DTI studies in SCD have been conducted, reporting heterogeneous results. We investigated microstructural changes in SCD in a larger, multicentric cohort.

Methods

271 participants with SCD, mild cognitive impairment (MCI) or Alzheimer’s dementia (AD) and healthy controls (CON) were included, recruited prospectively at nine centers of the observational DELCODE study. DTI was acquired using identical protocols. Using voxel-based analyses, we investigated fractional anisotropy (FA), mean diffusivity (MD) and mode (MO) in the white matter (WM). Discrimination accuracy was determined by cross-validated elastic-net penalized regression. Center effects were explored using variance analyses.

Results

MO and FA were lower in SCD compared to CON in several anterior and posterior WM regions, including the anterior corona radiata, superior and inferior longitudinal fasciculus, cingulum and splenium of the corpus callosum (p < 0.01, uncorrected). MD was higher in the superior and inferior longitudinal fasciculus, cingulum and superior corona radiata (p < 0.01, uncorrected). The cross-validated accuracy for discriminating SCD from CON was 67% (p < 0.01). As expected, the AD and MCI groups had higher MD and lower FA and MO in extensive regions, including the corpus callosum and temporal brain regions. Within these regions, center accounted for 3–15% of the variance.

Conclusions

DTI revealed subtle WM alterations in SCD that were intermediate between those in MCI and CON and may be useful to detect individuals with an increased risk for AD in clinical studies.

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Authors and Affiliations

  1. German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany

    Katharina Brueggen, Martin Dyrba, Ingo Kilimann & Stefan J. Teipel

  2. German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany

    Arturo Cardenas-Blanco, Coraline D. Metzger & Emrah Düzel

  3. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

    Anja Schneider, Michael Wagner, Sandra Röske, Annika Spottke, Janna Rudolph & Frank Jessen

  4. Department of Psychiatry, Medical Faculty, University of Cologne, Cologne, Germany

    Frank Jessen

  5. Institute of Cognitive Neurology and Dementia Research (IKND), Otto-Von-Guericke University, Magdeburg, Germany

    Coraline D. Metzger, Laura Dobisch & Emrah Düzel

  6. Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany

    Katharina Buerger & Daniel Janowitz

  7. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany

    Katharina Buerger

  8. Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany

    Anja Schneider, Klaus Fliessbach & Michael Wagner

  9. Institute of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany

    Oliver Peters & Felix Menne

  10. German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany

    Oliver Peters & Josef Priller

  11. Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany

    Josef Priller & Eike Spruth

  12. Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Göttingen, Germany

    Jens Wiltfang & Ruth Vukovich

  13. German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany

    Jens Wiltfang

  14. Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany

    Christoph Laske & Martina Buchmann

  15. German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany

    Christoph Laske & Martina Buchmann

  16. Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany

    Ingo Kilimann & Stefan J. Teipel

  17. Department of Psychiatry and Psychotherapy, Otto-Von-Guericke University, Magdeburg, Germany

    Coraline D. Metzger

  18. Department of Neurology, University of Bonn, Bonn, Germany

    Annika Spottke

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  1. Katharina Brueggen
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  2. Martin Dyrba
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  21. Ingo Kilimann
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  23. Emrah Düzel
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  24. Frank Jessen
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  25. Stefan J. Teipel
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The DELCODE Study Group

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Correspondence to Katharina Brueggen.

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The study has been approved by the local institutional review boards and ethics committees of the participating centers. It has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Brueggen, K., Dyrba, M., Cardenas-Blanco, A. et al. Structural integrity in subjective cognitive decline, mild cognitive impairment and Alzheimer’s disease based on multicenter diffusion tensor imaging. J Neurol 266, 2465–2474 (2019). https://doi.org/10.1007/s00415-019-09429-3

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