Aging Effects on White Matter (DTI)

November 27, 2011

Aging is associated with significant decline in the integrity of white matter (WM), and this decline contributes to age-related deficits in cognitive functions such as memory. WM integrity can be measured in vivo using diffusion tensor imaging (DTI). DTI assesses MR changes due to the movement of water molecules, which are more parallel in intact WM and more random in degraded WM. A common DTI measure is fractional anisotropy (FA), with smaller numbers indicating WM decline. Most DTI studies on aging have measured FA in large WM volumes. To assess age effects on specific tracts, we use a technique called DTI tractography. Using special software, various tracts (e.g., genu of corpus callosum) are identified by manually drawing blobs or planes crossed by the tract. In tracts color-coded with FA, age effects are obvious in individual subjects. Tracts are then averaged and color coded for the magnitude of age-related differences.

In one DTI tractography study (Davis et al., 2008), we found that age-related FA reductions decreased gradually from anterior to posterior brain regions, reversing the sequence of myelination during childhood development (last-in-first-out). Consistent with demyelination, age effects were stronger within radial diffusivity (RD), a measure linked to myelin integrity, than for axial diffusivity (AD), a measure linked to axonal integrity. Age-related FA reductions in posterior tracts were correlated with age-related deficits in visual memory tests and FA reductions in anterior tracts, with deficits in age-related deficits in executive function tests.

In another study (Davis et al., in press), we investigated whether WM deficits constrain functional connectivity in older adults. Participants were scanned with both fMRI and DTI while matching pairs of words presented to either the same or opposite visual fields (unilateral vs. bilateral). Cross-hemispheric communication was measured behaviorally as greater accuracy for bilateral than unilateral trials (bilateral processing advantage—BPA). At the neural level, hemispheric communication was indexed by functional and structural connectivity between contralateral PFC regions. The study yielded four findings. First, BPA was greater for older adults (OAs), in keeping with the idea that OAs distribute processing across hemispheres to a greater extent than younger adults. Second, OAs showed greater activity in contralateral PFC regions, consistent with HAROLD (see Compensatory Activity project). This effect occurred for bilateral but not for unilateral trials, linking HAROLD to cross-hemispheric communication. Third, functional connectivity between left and right PFC was greater for OAs than YAs during bilateral trials, suggesting that contralateral PFC regions overrecruited by OAs contribute to the network mediating task performance. Finally, FA in the genu corpus callosum was correlated with both bilateral trial accuracy and crosshemispheric functional connectivity, indicating that OAs’ ability to distribute processing across hemispheres is constrained by WM decline.

  • Davis, S.W., Dennis, N.A., Buchler, N.E.G., Madden, D.J., White, L.E., Cabeza, R. (2009).  Assessing the effects of aging on long white matter tracts using diffusion tensor imaging (DTI) tractography. Neuroimage , 46, 530-541. 
  • Davis, S. W., Kragel, J. Madden, D.J., & Cabeza, R. (in press). Cross-hemispheric communication and aging:  Linking behavior, brain activity, functional connectivity, and white matter integrity. Cerebral Cortex



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