Contributions of Prefrontal White Matter Integrity to Cognitive Performance in Healthy Aging

• Author / Creator

  Pietrasik, Wojciech

• Aging is well-known to produce changes in the brain at both the functional and anatomical level. Increased age is associated with general brain atrophy and a decline in cognitive abilities such as executive functioning, working memory, and processing speed.
  A key brain region responsible for these cognitive functions is the prefrontal cortex (PFC), which experiences disproportionately greater age-related degeneration than posterior areas of the brain. The PFC is a heterogenous structure and is often segmented into several functional subregions; it is believed these subregions may facilitate certain cognitive abilities, and damage specific to a certain subregion may result in distinct cognitive deficits in some domains while sparing others. The relationships between age, cognitive performance, and prefrontal grey matter structure have been investigated before; however, few in-vivo studies have examined how the white matter (WM) contained within these subregions is affected by aging, and whether age-related declines in WM integrity drive the declines in cognitive performance that comes with age.
  Therefore, the aim of this study is to use diffusion tensor imaging (DTI) to measure age differences in the WM integrity of prefrontal subregions and determine if WM integrity is a mediator of age-related cognitive decline.
  The study involved 140 participants aged 18-85 (62 men, 78 women). PFC WM was segmented into medial orbitofrontal (MOFC), lateral orbitofrontal (LOFC), medial prefrontal (MPFC), and dorsolateral prefrontal (DLPFC) components, and DTI parameters for each region were obtained. Participants were also evaluated on executive functions, working memory, processing speed, reaction times, and emotional recognition using various neuropsychological tests which were reduced to latent variables using factor analysis. To characterize the effects of age on DTI parameters more precisely, and measure their non-linear trajectories, higher order polynomial regression modeling was utilized, while structural equation modeling was used to test for mediation effects.
  We found that WM within all prefrontal subregions show age-related differences in DTI parameters, exhibiting decreases in fractional anisotropy (FA) values, increases in mean, radial, and axial diffusivities, and decreases in tract volumes and fiber counts with increased age. The majority of age effects were non-linear, best modeled using higher order powers of age in their regressions. Cognitive performance in most domains declined with increased age; however, after controlling for the effects of age, a general latent factor of PFC WM integrity was not found to mediate the age-related decline in cognitive performance. However, FA values specific to MOFC and LOFC tracts did predict performance in conceptual flexibility, visuospatial memory, reaction times, and theory of mind tasks and produced significant indirect effects of age on cognition. While FA values in the MOFC and right LOFC partially mediated age effects on cognitive ability, FA values in the left LOFC suppressed them, demonstrating the unique properties of prefrontal subregions.
  The findings in this study improve our understanding of WM aging. Although the vulnerability of prefrontal WM to aging has been documented, this is the first study that measured age effects on WM integrity within prefrontal subregions and investigated whether integrity mediates age-related cognitive decline. Prefrontal subregions do not display uniform WM aging and are uniquely associated with select cognitive functions, mediating the effects of age in certain cases

• Subjects / Keywords

  • white matter
  • diffusion tensor imaging
  • aging
  • cognition
  • cognitive testing
  • mediation
  • structural equation modeling

• Graduation date

  Fall 2021

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-qe9a-k906

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.