Fig. 6
Association between functional connectivity and early Aβ accumulation in BioFINDER. a and b show CSF Aβ42 correlations with whole-brain resting-state fMRI connectivity in non-demented subjects with normal Aβ PET and QC-passed fMRI data (n = 103). Nodes were grouped into the 7 networks and 2 subcortical regions in the connectograms (a and b). The connectograms show that the significant network component associated with CSF Aβ42 was qualitatively similar for the CSF+/PET− (a) and CSF-low/PET− (b) groups and consisted mostly of intra- and inter-DM connections. Intra-DM dominated and the strongest inter-DM connection was with the frontoparietal network. The network component of the CSF+/PET− group exhibited reduced connectivity with decreasing CSF Aβ42 (a), r = 0.91, p < 0.001. By contrast, in the qualitatively similar network component of the CSF-low/PET− group, decreasing Aβ42 was instead associated with increased connectivity (b), r = −0.85, p < 0.001. Panel c shows the dominating intra DM-reduction in connectivity for the CSF+/PET− group (a). In summary, a show that Aβ accumulation measured with CSF Aβ42 in early Aβ accumulators is associated with hypoconnectivity in intra- and inter-DM network links. b instead shows that in a population including subjects with even earlier indications of Aβ accumulation (CSF-low/PET−) Aβ accumulation is instead associated with hyperconnectivity in similar neuronal connections. Correlation coefficients (r) refer to Spearman correlation between summed connectivity and CSF Aβ42 levels. Age, gender, and APOE ε4 status was controlled for by partial correlation. Network components correlating with CSF Aβ42 were calculated using a method similar to the NBS algorithm (see “Methods for the BioFINDER study” for statistical details). Acronyms: BG basal ganglia, CSF-low normal CSF Aβ42 levels close to the abnormal cut-off (517–750 ng/L), DA dorsal attention, DM default mode, FP frontoparietal, FT frontotemporal, HI hippocampus, QC quality control, SM sensorimotor, VA ventral attention, VI visual network
