Evidence for cortical "disconnection" as a mechanism of age-related cognitive decline

Background: Normal aging is accompanied by a decline of cognitive abilities , and executive skills may be affected selectively, but the underlying mech anisms remain obscure and preventive strategies are lacking. It has been su ggested that cortical "disconnection" due to the loss of white matter fiber s may play an important role. But, to date, there has been no direct demons tration of structural disconnection in humans in vivo. Methods: The authors used diffusion tensor MRI to look for evidence of ultrastructural changes in cerebral white matter in a group of 20 elderly volunteers with normal co nventional MRI scans, and a group of 10 younger controls. The older group a lso underwent neuropsychological assessment. Results: Diffusional anisotrop y, a marker of white matter tract integrity, was reduced in the white matte r of older subjects and fell linearly with increasing age in the older grou p. Mean diffusivity was higher in the older group and increased with age. T hese changes were maximal in anterior white matter. In the older group, ant erior mean diffusivity correlated with executive function assessed by the T rail Making Test. Conclusions: These findings provide direct evidence that white matter tract disruption occurs in normal aging and would be consisten t with the cortical disconnection hypothesis of age-related cognitive decli ne. Maximal changes in anterior white matter provide a plausible structural basis for selective loss of executive functions. In addition to providing new information about the biological basis of cognitive abilities, diffusio n tensor MRI may be a sensitive tool for assessing interventions aimed at p reventing cognitive decline.