Myelin breakdown mediates age-related slowing in cognitive processing speed in healthy elderly men

Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of the corpus callosum myelinate later in brain development (late-myelinating white matter; LMWM) and are more vulnerable to breakdown due to the effects of normal aging. An in vivo MRI biomarker of myelin integrity (transverse relaxation rates; R₂) of LMWM was obtained for 38 very healthy elderly adult men (mean age=66.3years; SD=6.0; range=55-76). To evaluate regional specificity, we also assessed a contrasting early-myelinating region (splenium of the corpus callosum; SWM), which primarily contains axons involved in visual processing. CPS was assessed using the Trail Making Test. Results: LMWM R₂ and CPS measures were significantly correlated (r=.515, p=.0009), but no significant association between R₂ and CPS was detected in the splenium (p=.409). LMWM R₂, but not SWM R₂, was a significant mediator of the relationship between age and CPS (p=.037). Conclusions: In this very healthy elderly sample, age-related slowing in CPS is mediated by myelin breakdown in highly vulnerable late-myelinating regions but not in the splenium.