Within-person changes in the aging white matter: a meta-analysis and systematic review of longitudinal diffusion tensor imaging studies
Andrea Mendez Colmenares1, Ben Prytherch2, Michael Thomas1, Agnieszka Burzynska3
1Department of Psychology/Molecular, Cellular and Integrative Neurosciences, 2Statistics, 3Department of Human Development and Family Studies/Molecular, Cellular and Integrative Neurosciences, Colorado State University
Objective:
This combined meta-analysis and systematic review aimed to synthesize the evidence from longitudinal MRI studies on the magnitude, direction, spatial patterns, and possible modifiers of naturally occurring within-person changes in adult white matter (WM).
Background:
Age-related WM deterioration leads to cognitive impairments in older age even in the absence of dementia. Despite the emerging evidence from animal studies showing experience-induced changes in both myelin and axons, adult human WM is often perceived as static and not involved in neuroplasticity. However, because the evidence of experience-induced changes in the adult human WM microstructure is scarce, WM is rarely considered the primary target for treatments and interventions against cognitive decline.
Design/Methods:
We focused on the most widely used WM technique, diffusion tensor imaging (DTI).
Results:
Of 28 studies included, 22 (79%) reported negative changes in DTI fractional anisotropy (FA). The meta-analytic pooled effect among 2906 participants (66.4 ± 8.9 years) showed a decline in the whole WM FA (d = -0.12, 95% CI: -0.21 to -0.03, p = 0.008, average follow-up = 26 months), and this decline was greater with longer follow-up time. Similarly, we found a negative change of FA in the anterior corpus callosum (d = -0.14, 95% CI: -0.22 to -0.06, p = 0.003). Additionally, we found that the magnitude of change in FA was greater with advancing age, and greater in women than in men. In our qualitative review, we found that older age was associated with greater longitudinal change in FA in late-myelinating regions (e.g., anterior corpus callosum) than in early myelinating regions (e.g., superior corona radiata).
Conclusions:
Our results demonstrate that WM microstructure undergoes significant within-person changes in older age as measured with DTI. Understanding the naturally occurring within-person changes in adult WM will lay the foundation for studying the plastic and regenerative potential of WM in future clinical trials.