Aging-Related Microstructural Alterations Along the Length of the Cingulum Bundle

Abstract

The aim of this study was to investigate the aging-related structural changes of the cingulum, one of the major components of the limbic network, which has a critical role in emotion, attention, and memory. Thirty-five healthy young adults (22.3 ± 2.7 years) and 33 healthy older adults (69.5 ± 3.5 years) were recruited. Diffusion weighted imaging data were acquired with a b-value = 2000 sec/mm and 61 diffusion directions and 4 non-weighted images. The fiber directions in each voxel were based on the constrained spherical deconvolution model. The cingulum was segmented into three branches using deterministic tractography (subgenual, retrosplenial, and parahippocampal), using a region-of-interest-based approach. Atlas-based tractography was the method used to obtain the output tracts of each branch of the cingulum. Along-tract analysis was performed on each branch. We found a statistically significant change with aging in the left subgenual branch of the cingulum with a decrease in fractional anisotropy and axial diffusivity, as well as an increase in radial diffusivity. No statistically significant differences were found between young and older groups in the other two branches. This study adds to knowledge about how the cingulum changes structurally along its entire length during aging in a more detailed way, thanks to an advanced methodological approach.

Quantification of alterations in diffusion measures of white matter integrity associated with healthy aging

“…The small number of voxels showing associations of age with FA and RD in the hippocampal branch of the cingulum, and the lack of any association with AD or MD indicates this region of white matter is less affected than other white matter tracts. Similar to our findings, a study comparing young and older healthy adults found differences in the subgenual branch of the cingulum but no change in any diffusion measures in the parahippocampal segment of the cingulum [57].…”

“…We also found a small number of voxels showing a positive linear correlation of age with AD. Both increases and decreases of AD with age have been reported [20, 23, 33, 57]. Animal studies have attributed decreases in AD to acute axonal injury [13, 58].…”

“…However, only a very small number of voxels within the cingulum hippocampus ROI were associated with aging suggesting that this tract was not affected by age. Other studies have also observed differences in FA and RD only in parts of the cingulum, such as the superior portion but not posterior or inferior region [31], and the subgenual branch but not the parahippocampal segment of the cingulum [57].…”

The cingulum bundle: Anatomy, function, and dysfunction

“…A number of studies suggest that aging does not affect the cingulum uniformly but that region-specific effects can be observed. Some of the evidence is consistent with an age-related gradient along the long axis of the cingulum, in which frontal parts of the bundle appear most affected ( Catheline et al, 2010 ; Mårtensson et al, 2018 ; Sibilia et al, 2017 ; Yoon et al, 2008 ; see for review Chua et al, 2008 ). For example, older versus younger adults exhibited lower FA and AD as well as increased RD in the left subgenual cingulum, but not in the retrosplenial or parahippocampal cingulum ( Sibilia et al, 2017 ).…”

“…Some of the evidence is consistent with an age-related gradient along the long axis of the cingulum, in which frontal parts of the bundle appear most affected ( Catheline et al, 2010 ; Mårtensson et al, 2018 ; Sibilia et al, 2017 ; Yoon et al, 2008 ; see for review Chua et al, 2008 ). For example, older versus younger adults exhibited lower FA and AD as well as increased RD in the left subgenual cingulum, but not in the retrosplenial or parahippocampal cingulum ( Sibilia et al, 2017 ). Similarly, Jang et al (2016) investigated age differences across five portions of the cingulum (anterior, anterior superior, posterior superior, posterior and inferior cingulum) in 90 participants between 20 and 78 years of age.…”