Medial temporal lobe (MTL) – default‐mode network (DMN) functional connectivity disruption in the early stages of the progression of Alzheimer’s disease in a multimodal ADNI3 MP‐RAGE and EPI‐BOLD Advanced cohort

Background A cross-sectional same-session multi-modal analysis of T1 structural MRI and resting-state functional connectivity (rsfMRI) was performed to assess potential biomarkers the progression from cognitively normal (CN) significant memory concern (SMC) early late mild cognitive impairment (EMCI, LMCI). Methods An ADNI-3 EPI-BOLD Advanced protocol sub-population (N = 49) with baseline diagnosis CN 14), SMC 15), EMCI 11) LMCI 9), matched for age (p 0.37), education 0.65), gender 0.29), morphometric (FreeSurfer 7) fMRI (AFNI) measurements, processed a hybrid priori data-driven method identifying anchor-target ROI pairs in rsfMRI [1]. Anchor-target pairwise correlations were False Detection Rate (FDR) corrected parallel group-level one-way four-factor (CN, SMC, EMCI, LMCI) ANOVA post hoc t tests only. Results MRI. FreeSurfer subcortical segmentation, but not cortical thickness, yielded test (q 0.05, p* 2.8×10−3) left hippocampus. rsfMRI. 3-mm grid (r 6mm) seeds MTL 1,012 “anchors”. 3D (Fisher Z-transformed) correlation maps computed each subject anchor input ANOVA. Cluster (Nvox 20; p 0.02; P 3.45) F statistic 3,954 target ROIs. r 6mm placed at center mass cluster. pair FDR 0.005; 0.0067, estimated by permutation, N 1000) which identified 1,454 (ROI pairs). Post only on FDR-corrected 0.005) 34 SMC-CN (p* 1.1×10−4); 329 EMCI-CN 1.1×10−3); 78 LMCI-CN 2.6×10−4). For contrast, masks summed resulted 20-50 clusters bilaterally distributed DMN-associated regions. independent right hemisphere similar results. Conclusions approach applied ROIs multiple regions that predominantly, uniformly associated DMN. [1] Grajski, K. A., Bressler, S., ADNI. (2019). Neuroimage Clin. 2019;23:101860.