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 Basic cohort

Background A cross-sectional same-session multi-modal analysis (T1, rsfMRI) was applied to identify potential biomarkers of the progression from cognitively normal (CN) significant memory concern (SMC) and early late mild cognitive impairment (EMCI, LMCI) in Alzheimer’s disease. Methods An ADNI3 EPI-BOLD Basic sub-population (N = 133) with baseline diagnosis CN 45), SMC 46), EMCI 22), LMCI 20), matched for age (p 0.61), education 0.26), gender morphometric (FreeSurfer 7), fMRI (AFNI) measurements, processed a hybrid priori data-driven method that identified anchor-target ROI pairs rsfMRI [1]. pairwise correlations were False Detection Rate (FDR) corrected parallel group-level one-way four-factor (CN, SMC, EMCI, ANOVA post hoc t tests performed only. Results 3-mm grid (r 6mm) seeds left MTL yielded 488 “anchors”. 3D (Fisher Z-transformed) correlation maps computed each subject anchor input ANOVA. Cluster (Nvox 20; p 0.02; P 3.45) F statistic 1,774 target ROIs. r 6mm placed at center mass cluster. pair FDR (q 0.005; p* 0.0035, permutation, N 1000) which 1,179 tests. Post only on FDR-corrected 0.005) 163 SMC-CN (p* 6.8×10−4); 158 EMCI-CN 6.6×10−4); 120 LMCI-CN 5.1×10−4). The masks summed 35-44 clusters. same then independent runs using as regions amygdala, thalamus, substantia nigra, accumbens area. resultant spatial distribution predominantly, but not uniformly coincided DMN-associated regions. right hemisphere similar results. Conclusions approach ROIs multiple subcortical associated DMN. [1] Grajski, K. A., Bressler, S., ADNI. (2019). Neuroimage Clin. 2019;23:101860.