Association of Age and Structural Brain Changes With Functional Connectivity and Executive Function in a Middle-Aged to Older Population-Based Cohort

Maximilian Schulz; Carola Mayer; Eckhard Schlemm; Benedikt M Frey; Caroline Malherbe; Marvin Petersen; Jürgen Gallinat; Simone Kühn; Jens Fiehler; Uta Hanning; Raphael Twerenbold; Christian Gerloff; Bastian Cheng; Götz Thomalla

doi:10.3389/fnagi.2022.782738

Association of Age and Structural Brain Changes With Functional Connectivity and Executive Function in a Middle-Aged to Older Population-Based Cohort

Front Aging Neurosci. 2022 Feb 25:14:782738. doi: 10.3389/fnagi.2022.782738. eCollection 2022.

Authors

Affiliations

¹ Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
² Institute of Computational Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³ Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴ Department of Neuroradiological Diagnostics and Intervention, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁵ Department of Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁶ University Center of Cardiovascular Science, Department of Cardiology, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Abstract

Aging is accompanied by structural brain changes that are thought to underlie cognitive decline and dementia. Yet little is known regarding the association between increasing age, structural brain damage, and alterations of functional brain connectivity. The aim of this study was to evaluate whether cortical thickness and white matter damage as markers of age-related structural brain changes are associated with alterations in functional connectivity in non-demented healthy middle-aged to older adults. Therefore, we reconstructed functional connectomes from resting-state functional magnetic resonance imaging (MRI) (rsfMRI) data of 976 subjects from the Hamburg City Health Study, a prospective population-based study including participants aged 45-74 years from the metropolitan region Hamburg, Germany. We performed multiple linear regressions to examine the association of age, cortical thickness, and white matter damage quantified by the peak width of skeletonized mean diffusivity (PSMD) from diffusion tensor imaging on whole-brain network connectivity and four predefined resting state networks (default mode, dorsal, salience, and control network). In a second step, we extracted subnetworks with age-related decreased functional connectivity from these networks and conducted a mediation analysis to test whether the effect of age on these networks is mediated by decreased cortical thickness or PSMD. We observed an independent association of higher age with decreased functional connectivity, while there was no significant association of functional connectivity with cortical thickness or PSMD. Mediation analysis identified cortical thickness as a partial mediator between age and default subnetwork connectivity and functional connectivity within the default subnetwork as a partial mediator between age and executive cognitive function. These results indicate that, on a global scale, functional connectivity is not determined by structural damage in healthy middle-aged to older adults. There is a weak association of higher age with decreased functional connectivity which, for specific subnetworks, appears to be mediated by cortical thickness.

Keywords: age; cortical atrophy; functional connectivity; peak width of skeletonized mean diffusivity; resting state functional MR imaging.