Multicenter stability of resting state fMRI in the detection of Alzheimer's disease and amnestic MCI.
In monocentric studies, patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia exhibited alterations of functional cortical connectivity in resting-state functional MRI (rs-fMRI) analyses. Multicenter studies provide access to large sample sizes, but rs-fMRI may be particularly sensitive to multiscanner effects.



We used data from five centers of the "German resting-state initiative for diagnostic biomarkers" (psymri.org), comprising 367 cases, including AD patients, MCI patients and healthy older controls, to assess the influence of the distributed acquisition on the group effects. We calculated accuracy of group discrimination based on whole brain functional connectivity of the posterior cingulate cortex (PCC) using pooled samples as well as second-level analyses across site-specific group contrast maps.



We found decreased functional connectivity in AD patients vs. controls, including clusters in the precuneus, inferior parietal cortex, lateral temporal cortex and medial prefrontal cortex. MCI subjects showed spatially similar, but less pronounced, differences in PCC connectivity when compared to controls. Group discrimination accuracy for AD vs. controls (MCI vs. controls) in the test data was below 76% (72%) based on the pooled analysis, and even lower based on the second level analysis stratified according to scanner. Only a subset of quality measures was useful to detect relevant scanner effects.



Multicenter rs-fMRI analysis needs to employ strict quality measures, including visual inspection of all the data, to avoid seriously confounded group effects. While pending further confirmation in biomarker stratified samples, these findings suggest that multicenter acquisition limits the use of rs-fMRI in AD and MCI diagnosis.
Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany; DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany.
Stefan J
SJ
Teipel
Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany.
Alexandra
A
Wohlert
Institute of Cognitive Neurology and Dementia Research (IKND), Department of Psychiatry and Psychotherapy, Otto von Guericke University, Germany and German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Coraline
C
Metzger
Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Timo
T
Grimmer
Department of Neuroradiology of Klinikum rechts der Isar, Technische Universität München, Department of Psychiatry of Klinikum rechts der Isar, TUM-Neuroimaging Center, Einsteinstr. 1, 81675 Munich, Germany.
Christian
C
Sorg
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
Michael
M
Ewers
Department of Psychiatry, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
Eva
E
Meisenzahl
Department of Psychiatry and Psychotherapy, Section of Gerontopsychiatry and Neuropsychology, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Old Age Psychiatry, Bern, Switzerland.
Stefan
S
Klöppel
Leibniz Institute for Neurobiology, Magdeburg, Germany; Department of Psychiatry, University Tübingen, Germany.
Viola
V
Borchardt
DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany.
Michel J
MJ
Grothe
Leibniz Institute for Neurobiology, Magdeburg, Germany; Department of Psychiatry, University Tübingen, Germany.
Martin
M
Walter
DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany.
Martin
M
Dyrba
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D001931:Brain Mapping; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging*; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging*; D010100:Oxygen / Q000097:blood; D012146:Rest
D010100:Oxygen