Accelerated brain aging in chronic low back pain

Abstract

Chronic low back pain (CLBP) is a leading cause of disability and is associated with neurodegenerative changes in brain structure. These changes lead to impairments in cognitive function and are consistent with those seen in aging, suggesting an accelerated aging pattern. In this study we assessed this using machine-learning estimated brain age (BA) as a holistic metric of morphometric changes associated with aging. Structural imaging data from 31 non-depressed CLBP patients and 32 healthy controls from the Pain and Interoception Imaging Network were included. Using our previously developed algorithm, we estimated BA per individual based on grey matter density. We then conducted multivariable linear modeling for effects of group, chronological age, and their interaction on BA. We also performed two voxel-wise analyses comparing grey matter density between CLBP and control individuals and the association between gray matter density and BA. There was an interaction between CLBP and greater chronological age on BA such that the discrepancy in BA between healthy and CLBP individuals was greater for older individuals. In CLBP individuals, BA was not associated with sex, current level of pain, duration of CLBP, or mild to moderate depressive symptoms. CLBP individuals had lower cerebellar grey matter density compared to healthy individuals. Brain age was associated with lower gray matter density in numerous brain regions. CLBP was associated with greater BA, which was more profound in later life. BA as a holistic metric was sensitive to differences in gray matter density in numerous regions which eluded direct comparison between groups.

Keywords: Aging; Chronic low back pain; Machine learning; Structural neuroimaging.

Figure 1:

CLBP is associated with greater brain age over chronological age - Association between chronological age and predicted brain age in healthy controls (HC, blue) and those with CLBP (red) are shown. Trendlines and 95% confidence intervals (shaded areas) are plotted as well. The CLBP group showed a significantly steeper trend of brain age increases over chronological age representative of a discrepancy in aging exacerbated over the lifespan.

Figure 2:

Individuals with CLBP have lower gray matter density - Regions showing significant differences in gray matter density between HC and CLBP (corrected for multiple comparisons). Independent t-test values are plotted on the brain, where cooler colors indicate HC < CLBP while warmer colors indicate HC > CLBP. Brains are plotted using BrainNet Viewer. Note that the cerebellum is shown in radiological view (left-right flipped).

Figure 3:

Greater brain age is associated with lower gray matter density in numerous regions - Regions showing significant association between gray matter density and brain age residual (regressed out sex, age (centered), and age (centered) squared), corrected for multiple comparisons, are shown. Colors indicate the t-value for the regression between gray matter density and brain age residual while adjusting for sex, age (centered), and age (centered) squared. Cooler colors indicate that lower gray matter density is associated with greater brain age (no regions in the opposite direction). Brains are plotted using BrainNet Viewer.