Cerebral White Matter Integrity Mediates Adult Age Differences in Cognitive Performance

Abstract

Previous research has established that age-related decline occurs in measures of cerebral white matter integrity, but the role of this decline in age-related cognitive changes is not clear. To conclude that white matter integrity has a mediating (causal) contribution, it is necessary to demonstrate that statistical control of the white matter-cognition relation reduces the magnitude of age-cognition relation. In this research, we tested the mediating role of white matter integrity, in the context of a task switching paradigm involving word categorization. Participants were 20 healthy, community-dwelling older adults (60–85 years), and 20 younger adults (18–27 years). From diffusion tensor imaging (DTI) tractography, we obtained fractional anisotropy (FA) as an index of white matter integrity in the genu and splenium of the corpus callosum and the superior longitudinal fasciculus (SLF). Mean FA values exhibited age-related decline consistent with a decrease in white matter integrity. From a model of reaction time distributions, we obtained independent estimates of the decisional and nondecisional (perceptual-motor) components of task performance. Age-related decline was evident in both components. Critically, age differences in task performance were mediated by FA in two regions: the central portion of the genu, and splenium-parietal fibers in the right hemisphere. This relation held only for the decisional component and was not evident in the nondecisional component. This result is the first demonstration that the integrity of specific white matter tracts is a mediator of age-related changes in cognitive performance.

Reduced White Matter Integrity Is Related to Cognitive Instability

“…The present results confirm a relationship between mRT from the congruent condition and DTI parameters, in that significant effects were seen for AD and MD in the genu and middle sections (body) of the corpus callosum, and in the left anterior thalamic radiation and forceps minor for AD. Several studies report that various measures of information processing speed are related to microstructural characteristics of WM in the genu of corpus callosum (Bucur et al, 2008;Madden et al, 2009), in agreement with the present results from the congruent condition. However, the anatomical locations and which DTI parameter shows the strongest effects vary between studies, likely partly due to different cognitive tasks.…”

“…Due to the spatial distribution of highly specialized brain areas (Gläscher et al, 2010) and that the main function of the myelin sheet is to isolate the axons, thereby facilitating conduction of action potentials over long distances, individual differences in WM structure are expected to affect cognitive performance, e.g., processing speed (O'Sullivan et al, 2001;Madden et al, 2004Madden et al, , 2009Schulte et al, 2005;Deary et al, 2006;Grieve et al, 2007;Bucur et al, 2008;Correia et al, 2008;Turken et al, 2008;Kennedy and Raz, 2009;Vernooij et al, 2009). The present results confirm a relationship between mRT from the congruent condition and DTI parameters, in that significant effects were seen for AD and MD in the genu and middle sections (body) of the corpus callosum, and in the left anterior thalamic radiation and forceps minor for AD.…”

“…This would lead to less distinct cortical representations, poorer cognitive performance, and increased performance variability, suggesting that lower WM integrity may be associated with IIV. More than a dozen studies have reported relationships between mental processing speed and diffusion tensor imaging (DTI) (O'Sullivan et al, 2001;Madden et al, 2004Madden et al, , 2009Schulte et al, 2005;Deary et al, 2006;Grieve et al, 2007;Bucur et al, 2008;Correia et al, 2008;Turken et al, 2008;Kennedy and Raz, 2009;Vernooij et al, 2009), but data are lacking for IIV. Response variability has been related to WM volume Walhovd and Fjell, 2007;Ullén et al, 2008) and hyperintensities (Bunce et al, 2007).…”

Multimodal imaging of the self-regulating developing brain

“…Furthermore, forceps major is not assumed to be especially important for cognitive control. This assumption does not exclude the possibility that maturation of specific WM tracts can be related to more specific cognitive functions (57)(58)(59)(60), but it will likely also have general beneficial effects on major cognitive functions through facilitation of processing speed (61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71).…”

Deficit in switching between functional brain networks underlies the impact of multitasking on working memory in older adults

“…35 and 36) and it has been proposed that age-associated declines in WM and long-term memory are a result of reorganization in the functional integration of brain regions, in addition to general dysfunction of specific regions and white matter connections (37)(38)(39). For example, Grady et al (40) showed that functional connectivity between the hippocampus and prefrontal cortex differs between younger and older adults, such that older adults exhibit connectivity to more dorsolateral areas (rather than ventral areas) in the prefrontal cortex.…”