Multicenter stability of resting state fMRI in the detection of Alzheimer's disease and amnestic MCI

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.