title: Myelin breakdown mediates age-related slowing in cognitive processing speed in healthy elderly men.
abstract: 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).
  
  
  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; R(2)) of LMWM was obtained for 38 very healthy elderly adult men (mean age=66.3 years; 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 R(2) and CPS measures were significantly correlated (r=.515, p=.0009), but no significant association between R(2) and CPS was detected in the splenium (p=.409). LMWM R(2), but not SWM R(2), 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.
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States. plu@mednet.ucla.edu
authors.forename: Po H
authors.initials: PH
authors.lastname: Lu
authors.forename: Grace J
authors.initials: GJ
authors.lastname: Lee
authors.forename: Todd A
authors.initials: TA
authors.lastname: Tishler
authors.forename: Michael
authors.initials: M
authors.lastname: Meghpara
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.forename: George
authors.initials: G
authors.lastname: Bartzokis
mesh_terms: D000367:Age Factors; D000368:Aged; D003071:Cognition; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008606:Mental Processes / Q000502:physiology*; D008875:Middle Aged; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D009483:Neuropsychological Tests; D013997:Time Factors