Impact of vascular factors and tau deposition on functional brain network connectivity in participants of the Framingham Heart Study

Abstract

AbstractBackgroundThe goal of this study was to determine whether vascular factors, expressed as the Framingham Stroke Risk Profile (FSRP), and/or tau deposition impact functional brain connectivity within and between functional brain networks i.e. default mode, frontoparietal, dorsal attention, and ventral attention networks. Regional blood flow measured by fMRI has been used to infer functional brain connectivity. Regions with synchronized blood flow are thought to be functionally connected while areas that have desynchronized blood flow are thought to be less functionally connected. Factors such as age have been linked to a reduction in functional connectivity.Method224 participants (mean age 54±8, 56% men) from the third generation of the Framingham Heart Study were imaged at Boston University from September 2015 to August 2018. Each participant had a high resolution MPRAGE T1 and a seven‐minute resting state fMRI scan. The T1 scans were processed using Freesurfer v6.0 and the resting state fMRI scans with FSL. Functional networks were constructed using the Yeo 7 network atlas (Yeo, 2011). Correlations within and between the functional brain networks were generated and z corrected. The relationship between FSRP, regional amyloid using the Pittsburgh B ligand, tau deposition using Flortaucipir, and functional connectivity were assessed using linear regression models adjusted for age, sex and interval between FSRP (or amyloid and tau) measurements and fMRI.ResultVascular risk factors and tau deposition had opposite impacts on functional connectivity. Increases in the FSRP were linked to increased functional connectivity between the default mode and visual networks, as well as the frontoparietal. Conversely, tau deposition in the inferior temporal, precuneus, and entorhinal cortices was linked to a reduction in functional connectivity within the frontoparietal network, between the default mode and somatomotor, and dorsal attention and somatomotor networks.ConclusionVascular risk factors appear to relate to an enhancement of functional connectivity while regional tau deposition appears to have an adverse impact on both within and between network connectivity. It is plausible that these changes in functional connectivity represent a compensatory response in the brain to alterations in vascular function and the presence of neuropathology in order to maintain cognitive abilities.