Diffusion tensor images of cerebral white matter; the directionality of water motion is shown in red (left/right), blue (dorsal/ventral) and green (anterior/posterior). Courtesy of Tom Barrick, MARIARC, University of Liverpool, UK.

A gradual decline in our cognitive abilities is one of the less welcome aspects of normal aging. Our 'executive skills' — high-level cognitive functions that allow us to perform complex goal-directed tasks — are often preferentially affected, but despite the fact that such age-related deficits in cognition are well documented, the underlying structural and functional brain changes remain largely unknown. By using the recently developed method of diffusion tensor magnetic resonance imaging, O'Sullivan et al. provide the first direct in vivo evidence that aging might be associated with the structural 'disconnection' of regions of the neocortex involved in cognitive processing.

In cerebral white matter, axonal membranes and myelin restrict the motion of water, such that it tends to move in the direction of fibre tracts. In diffusion tensor imaging, this directionality can be quantified by fractional anisotropy (FA), which varies from zero (isotropic; equal diffusion in all directions) to 1 (unidirectional diffusion). A directionally averaged measure of diffusion — mean diffusivity — can also be obtained. If the integrity of a white matter tract is disrupted — for example, if the tract becomes demyelinated or less tightly packed — FA will decrease, whereas diffusivity will increase.

O'Sullivan et al. used these measures to examine the status of white matter in the brains of healthy volunteers. They showed that white matter FA declines with age, whereas mean diffusivity increases, consistent with an age-related deterioration of white matter tracts. When the sampled volume was divided into anterior, middle and posterior regions, they found that anterior white matter was disrupted most, whereas posterior areas were affected least; moreover, the integrity of anterior white matter seemed to decline more rapidly with age than that of more posterior regions. These data point to a selective disruption of frontal connections with advancing age, consistent with a progressive loss of executive skills, which are served by frontal cortical areas.

To test whether a disruption of cortical connections could account for a decline in cognitive ability, O'Sullivan et al. examined the relationship between measures of water diffusion and the scores of volunteers in tests of executive function and verbal fluency. They found that performance in an executive test correlated with mean diffusivity in anterior regions, whereas verbal fluency scores, which would be expected to depend on connections between temporal and frontal regions, correlated with the FA of middle white matter. So, the structural findings in this study agree with what is known about the functional anatomy of executive and verbal tasks.

O'Sullivan et al. present compelling evidence that age-related cognitive decline, and executive dysfunction in particular, could involve the disconnection of components of neurocognitive networks. Diffusion tensor imaging provides a means of characterizing further the structural correlates of aging, a quest that could ultimately lead to a means of preserving our cortical connections, and the cognitive functions that they serve, into old age.