Multicenter resting state functional connectivity in prodromal and dementia stages of Alzheimer's disease

Stefan J. Teipel, Coraline D. Metzger, Frederic Brosseron, Katharina Buerger, Katharina Brueggen, Cihan Catak, Dominik Diesing, Laura Dobisch, Klaus Fließbach, Christiana Franke, Michael T. Heneka, Ingo Kilimann, Barbara Kofler, Felix Menne, Oliver Peters, Alexandra Polcher, Josef Priller, Anja Schneider, Annika Spottke, Eike J. SpruthManuela Thelen, René J. Thyrian, Michael Wagner, Emrah Düzel, Frank Jessen, Martin Dyrba

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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.

Original languageEnglish
Pages (from-to)801-813
Number of pages13
JournalJournal of Alzheimer's Disease
Issue number3
StatePublished - 2018
Externally publishedYes


  • Aging
  • Diagnostic accuracy
  • Functional MRI
  • Multicenter
  • Subjective cognitive decline


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