Longitudinal Changes of Structural and Functional Connectivity and Correlations with Neurocognitive Metrics

Revealing brain functional and micro-structural changes over a relatively short period at individual levels are especially important given that many risks associated with age including vascular and neuroinflammation increases and could confound the baseline fMRI parametric images. Cellular-level axonal injury and/or demyelination as well as dispersed mesoscopic level substance abnormal aggregation and structural/functional abnormality could occur in short subacute/acute phases, while literatures related to longitudinal changes with age are limited with only our previous fMRI findings. Longitudinal data were used to characterize these multi-parameters including random intercept and interval per individual. No significant age by gender interactions have been found to either DTI fractional anisotropy (FA) or diffusivity metrics. The interval effective regions showed longitudinal change of FA and radial diffusivity (RD)/axial diffusivity (AX) values remained similar to the aging results found with cross-sectional data. Significant correlations between DTI and fMRI metrics as well as between imaging and neurocognitive data including speed and memory were found. Our results indicate significant and consistent age, gender and apolipoprotein E (APOE) genotypic effects on structural and functional connectivity at both short-interval and cross-sectional ranges, together with correlational neurocognitive functions. We found longitudinal changes in both DTI and fcMRI in regions were similar to those demonstrating cross-sectional effects of age; for instance decreased fcMRI in DMN but increased fcMRI in anti-correlated DAN networks. The APOE genotypic signatures of FA and functional connectivity suggested possible tight associations between myelin/neuronal activation and APOE gene, indicating different roles of APOE alleles on brain structural conductivity, demyelination and neuroplasticity. Taken together, our neuroimaging and correlational neurocognitive results indicate significant and consistent age, gender and APOE genotypic effects on structural and functional connectivity at both baseline and longitudinal short-interval ranges.