Longitudinal Changes in White Matter Tract Integrity across the Adult Lifespan and Its Relation to Cortical Thinning

A causal link between decreases in white matter (WM) integrity and cortical degeneration is assumed, but there is scarce knowledge on the relationship between these changes across the adult human lifespan. We investigated changes in thickness throughout the cortical mantle and WM tract integrity derived from T1 and diffusion weighted magnetic resonance imaging (MRI) scans in 201 healthy adults aged 23–87 years over a mean interval of 3.6 years. Fractional anisotropy (FA), mean (MD), radial (RD) and axial (AD) diffusivity changes were calculated for forceps minor and major and eight major white matter tracts in each hemisphere by use of a novel automated longitudinal tractography constrained by underlying anatomy (TRACULA) approach. We hypothesized that increasing MD and decreasing FA across tracts would relate to cortical thinning, with some anatomical specificity. WM integrity decreased across tracts non-uniformly, with mean annual percentage decreases ranging from 0.20 in the Inferior Longitudinal Fasciculus to 0.65 in the Superior Longitudinal Fasciculus. For most tracts, greater MD increases and FA decreases related to more cortical thinning, in areas in part overlapping with but also outside the projected tract endings. The findings indicate a combination of global and tract-specific relationships between WM integrity and cortical thinning.

clusters are displayed in Figure3. For FA, positive change relationships with cortical thickness were found in left hemisphere superior temporal, retrosplenial, and precuneus cortices, as well as bilaterally in the superior frontal cortex. Some overlap with tract endings in left occipital cortex was observed.
Forceps Minor. Negative thickness change -MD change relationships were found laterally in left hemisphere inferior temporal and a frontal cluster including the pars opercularis, as well as right hemisphere superior and middle temporal, and a orbitofrontal cluster. Both frontal and anterior cingulate clusters were in close proximity of tract endings, but with a small degree of overlap.
Medially a right hemisphere anterior cingulate cluster was found. Negative thickness change -FA change clusters were detected bilaterally in the caudal middle frontal cortex, as well as in right hemisphere inferior parietal cortex.
Inferior Longitudinal Fasciculus. Negative thickness change -MD change relationships were predominantly observed in the right hemisphere, with lateral clusters being found laterally in frontal (superior and pars triangularis) and middle temporal cortices, close to tract endpoints, and medially in superior frontal and paracentral cortices. Additionally, a negative cluster was observed in fusiform gyrus.
Superior Longitudinal Fasciculus -Temporal bundle. Four negative thickness change -MD change clusters were detected in the right hemisphere, laterally in inferior temporal, inferior parietal and frontal (pars triangularis and superior frontal) cortices, and medially in superior frontal cortex. A negative left hemisphere cluster comprising the precentral gyrus as well as supramarginal cortex, with some degree of overlap with tract endings, was also found. Anterior Thalamic Radiation. Two negative thickness change -MD change clusters were identified in the right hemisphere; one comprising a small portion of inferior temporal cortex laterally and fusiform gyrus medially, and one orbitofrontalanterior cingulate cluster. Furthermore, a positive thickness change -FA change cluster was also found orbitofrontally in the right hemisphere. The observed frontal clusters appears to overlap to some extent with tract endings.

Superior
Cingulumcingulate gyrus (supracallosal) bundle. Three negative thickness change -MD change clusters were found laterally in the left hemisphere; two frontal (caudal middle frontal and rostral middle frontal) and one in the supramarginal gyrus. Furthermore, a small negative right hempisphere cluster in the inferior parietal cortex was identified.

Cingulum -Angular (infracallosal) bundle. Three negative thickness change -MD change clusters
were found in the right hemisphere; one comprising parts of superior parietal as well as pre central cortices, one in the middle temporal cortex, and one frontal cluster covering regions of pars triangularis. One such cluster was detected in in the left hemisphere, which included portions of middle and superior temporal cortices.
Corticospinal Tract. Two negative thickness change -MD change clusters were identified laterally in the right hemisphere and three in left hemisphere. In the right hemisphere these were located in middle temporal and frontal (caudal middle frontal) cortices, and in the right hemisphere clusters were found in inferior parietal, supramarginal and frontal (pars opercularis) cortices. Additionally, a small positive thickness change -FA change cluster was identified frontally (caudal middle frontal) in the right hemisphere, and two positive clusters covering precentral as well as postcentral and supramarginal cortices were found in the left hemisphere.