Neurodegeneration in medial temporal lobe subregions propagates within distinct functional networks in the AD continuum

Background The medial temporal lobe (MTL) is extensively connected to the rest of the brain through two specific networks: the anterior‐temporal (AT) and the posterior‐medial (PM) systems. As neurodegeneration is thought to occur along specific networks, our aim was to evaluate whether atrophy in perirhinal (PRC) vs parahippocampal cortices (PHC) ‐ two MTL nodes of the AT vs PM systems, respectively ‐ covary over time with distinct brain regions reflecting the AT vs PM networks. Method Longitudinal T1‐weighted images (up to 3 scans, span: 1.73±0.49 years) of 117 Ab‐ Cognitively Normal elderly (CN), 65 Ab+ CN, 148 Ab+ MCI and 19 Ab+ AD individuals from ADNI were included. Annualized atrophy rates of PRC and PHC were estimated with an unbiased deformation‐based morphometry method. Whole‐brain cortical thickness annualized atrophy rates were estimated using ANTs. Voxel‐wise correlations between MTL measures and whole‐brain maps were performed to highlight structural covariance patterns [P cluster(corr) <0.05, P voxel(uncorr) <0.01]. Functional connectivity analyses (seed‐based) were employed to define the AT and PM networks [P cluster(corr) <0.05, P voxel(uncorr) <0.01] in an independent sample of 68 CN older adults. The overlap between structural covariance patterns and the AT and PM networks was visually inspected. T‐maps from the voxel‐wise correlations were used to calculate goodness of fit (GOF) indices with the AT and PM networks (GOF=t inside ‐t outside ). Result Functional connectivity analyses revealed two distinct networks: the AT network encompasses the amygdala and the temporopolar cortex extending posteriorly to inferior and middle temporal gyri while the PM network encompasses the posterior cingulate cortex, the precuneus, the cuneus, the angular and occipital gyri and the right insula (Figure 1‐a). PRC structurally covaried with the amygdala and the left temporopolar cortex, overlapping with the AT network (Figure 1‐b,c). In contrast, PHC covaried with the posterior cingulate cortex, the precuneus, the cuneus and the angular and occipital gyri, overlapping with the PM network (Figure 1‐b,d). PRC covariance showed best GOF with the AT system (1.10 vs ‐0.50 for PM) and PHC covariance showed best GOF with the PM system (0.92 vs ‐0.33 for AT). Conclusion Overall, MTL atrophy propagates within two distinct networks over time, recapitulating the typical atrophy pattern in AD.