Stefan J Teipel1,2, Coraline D Metzger3,4,5, Frederic Brosseron6,7, Katharina Buerger8,9, Katharina Brueggen2, Cihan Catak9, Dominik Diesing10, Laura Dobisch5, Klaus Fliebach6,7, Christiana Franke11,12, Michael T Heneka6,7, Ingo Kilimann1,2, Barbara Kofler6,13, Felix Menne10,12, Oliver Peters10,12, Alexandra Polcher6, Josef Priller11,12, Anja Schneider6,7, Annika Spottke6,14, Eike J Spruth11,12, Manuela Thelen6,15, René J Thyrian16, Michael Wagner6,7, Emrah Düzel3,5, Frank Jessen6,15, Martin Dyrba2. 1. Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany. 2. German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany. 3. Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany. 4. Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany. 5. German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. 6. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. 7. Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany. 8. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. 9. Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany. 10. Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany. 11. Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany. 12. German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany. 13. Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany. 14. Department of Neurology, University of Bonn, Bonn, Germany. 15. Department of Psychiatry, University of Cologne, Cologne, Germany. 16. German Center for Neurodegenerative Diseases (DZNE), Greifswald, Germany.
Abstract
BACKGROUND: Alterations of intrinsic networks from resting state fMRI (rs-fMRI) have been suggested as functional biomarkers of Alzheimer's disease (AD). OBJECTIVE: To determine the diagnostic accuracy of multicenter rs-fMRI for prodromal and preclinical stages of AD. METHODS: We determined rs-fMRI functional connectivity based on Pearson's correlation coefficients and amplitude of low-frequency fluctuation in people with subjective cognitive decline, people with mild cognitive impairment, and people with AD dementia compared with healthy controls. We used data of 247 participants of the prospective DELCODE study, a longitudinal multicenter observational study, imposing a unified fMRI acquisition protocol across sites. We determined cross-validated discrimination accuracy based on penalized logistic regression to account for multicollinearity of predictors. RESULTS: Resting state functional connectivity reached significant cross-validated group discrimination only for the comparison of AD dementia cases with healthy controls, but not for the other diagnostic groups. AD dementia cases showed alterations in a large range of intrinsic resting state networks, including the default mode and salience networks, but also executive and language networks. When groups were stratified according to their CSF amyloid status that was available in a subset of cases, diagnostic accuracy was increased for amyloid positive mild cognitive impairment cases compared with amyloid negative controls, but still inferior to the accuracy of hippocampus volume. CONCLUSION: Even when following a strictly harmonized data acquisition protocol and rigorous scan quality control, widely used connectivity measures of multicenter rs-fMRI do not reach levels of diagnostic accuracy sufficient for a useful biomarker in prodromal stages of AD.
BACKGROUND: Alterations of intrinsic networks from resting state fMRI (rs-fMRI) have been suggested as functional biomarkers of Alzheimer's disease (AD). OBJECTIVE: To determine the diagnostic accuracy of multicenter rs-fMRI for prodromal and preclinical stages of AD. METHODS: We determined rs-fMRI functional connectivity based on Pearson's correlation coefficients and amplitude of low-frequency fluctuation in people with subjective cognitive decline, people with mild cognitive impairment, and people with AD dementia compared with healthy controls. We used data of 247 participants of the prospective DELCODE study, a longitudinal multicenter observational study, imposing a unified fMRI acquisition protocol across sites. We determined cross-validated discrimination accuracy based on penalized logistic regression to account for multicollinearity of predictors. RESULTS: Resting state functional connectivity reached significant cross-validated group discrimination only for the comparison of AD dementia cases with healthy controls, but not for the other diagnostic groups. AD dementia cases showed alterations in a large range of intrinsic resting state networks, including the default mode and salience networks, but also executive and language networks. When groups were stratified according to their CSF amyloid status that was available in a subset of cases, diagnostic accuracy was increased for amyloid positive mild cognitive impairment cases compared with amyloid negative controls, but still inferior to the accuracy of hippocampus volume. CONCLUSION: Even when following a strictly harmonized data acquisition protocol and rigorous scan quality control, widely used connectivity measures of multicenter rs-fMRI do not reach levels of diagnostic accuracy sufficient for a useful biomarker in prodromal stages of AD.
Authors: Meret Herdick; Martin Dyrba; Hans-Christian J Fritz; Slawek Altenstein; Tommaso Ballarini; Frederic Brosseron; Katharina Buerger; Arda Can Cetindag; Peter Dechent; Laura Dobisch; Emrah Duezel; Birgit Ertl-Wagner; Klaus Fliessbach; Silka Dawn Freiesleben; Ingo Frommann; Wenzel Glanz; John Dylan Haynes; Michael T Heneka; Daniel Janowitz; Ingo Kilimann; Christoph Laske; Coraline D Metzger; Matthias H Munk; Oliver Peters; Josef Priller; Nina Roy; Klaus Scheffler; Anja Schneider; Annika Spottke; Eike Jakob Spruth; Maike Tscheuschler; Ruth Vukovich; Jens Wiltfang; Frank Jessen; Stefan Teipel; Michel J Grothe Journal: Neuroimage Clin Date: 2020-11-11 Impact factor: 4.881
Authors: Stefan J Teipel; Katharina Brüggen; Anna Gesine Marie Temp; Kristina Jakobi; Marc-André Weber; Christoph Berger Journal: Front Neurol Date: 2021-06-17 Impact factor: 4.003