Multimodal Magnetic Resonance Imaging Assessment of White Matter Aging Trajectories Over the Lifespan of Healthy Individuals

Department of Psychiatry, The David Geffen School of Medicine at UCLA, Los Angeles, California
Biological psychiatry (Impact Factor: 10.26). 09/2012; 72(12). DOI: 10.1016/j.biopsych.2012.07.010
Source: PubMed


Postmortem and volumetric imaging data suggest that brain myelination is a dynamic lifelong process that, in vulnerable late-myelinating regions, peaks in middle age. We examined whether known regional differences in axon size and age at myelination influence the timing and rates of development and degeneration/repair trajectories of white matter (WM) microstructure biomarkers.

Healthy subjects (n = 171) 14-93 years of age were examined with transverse relaxation rate (R(2)) and four diffusion tensor imaging measures (fractional anisotropy [FA] and radial, axial, and mean diffusivity [RD, AxD, MD, respectively]) of frontal lobe, genu, and splenium of the corpus callosum WM (FWM, GWM, and SWM, respectively).

Only R(2) reflected known levels of myelin content with high values in late-myelinating FWM and GWM regions and low ones in early-myelinating SWM. In FWM and GWM, all metrics except FA had significant quadratic components that peaked at different ages (R(2) < RD < MD < AxD), with FWM peaking later than GWM. Factor analysis revealed that, although they defined different factors, R(2) and RD were the metrics most closely associated with each other and differed from AxD, which entered into a third factor.

The R(2) and RD trajectories were most dynamic in late-myelinating regions and reflect age-related differences in myelination, whereas AxD reflects axonal size and extra-axonal space. The FA and MD had limited specificity. The data suggest that the healthy adult brain undergoes continual change driven by development and repair processes devoted to creating and maintaining synchronous function among neural networks on which optimal cognition and behavior depend.

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    • "al . , 2013 ) . Developmentally , myelination occurs as one of the final stages of brain development . In humans , most myelination takes place during the first 20 years of postnatal life ( Lebel et al . , 2008 ) . While the bulk of myelination occurs in relatively early postnatal life , it is now clear that myelination continues throughout life ( Bartzokis et al . , 2012 ; Young et al . , 2013 ) . Coinciding with their later development , oligodendrocytes are the final cells of the CNS to mature . Nevertheless , oligodendrocyte precursor cells ( OPCs ) are present at embryonic day 12 . 5 in mice . Production of OPCs is localized to distinct areas , thus , migration of this cell type throughout the brain"
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    • "In humans, most myelination takes place during the first 20 years of postnatal life (Lebel et al., 2008). While the bulk of myelination occurs in relatively early postnatal life, it is now clear that myelination continues throughout life (Bartzokis et al., 2012;Young et al., 2013). Coinciding with their later development, oligodendrocytes are the final cells of the CNS to mature. "
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    • "During adolescence, reduction in CT might be associated with neuronal pruning (Kanai and Rees 2011; Huttenlocher and Dabholkar 1997), which results in more efficient cortical networks (Kharitonova et al. 2013). The frontal lobes are the last region to complete the myelination process; with frontal lobe myelination peaking in the 4th decade of life (Bartzokis et al. 2012). Therefore, thicker cortex in our healthy adult population may confer a functional disadvantage because it reflects either insufficient pruning or myelination. "
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