Age‐related differences in multiple measures of white matter integrity: A diffusion tensor imaging study of healthy aging

Abstract

Diffusion tensor imaging (DTI) measures diffusion of molecular water, which can be used to calculate indices of white matter integrity. Early DTI studies of aging primarily focused on two global measures of integrity; the average rate (mean diffusivity, MD) and orientation coherence (fractional anisotropy, FA) of diffusion. More recent studies have added measures of water movement parallel (axial diffusivity, AD) and perpendicular (radial diffusivity, RD) to the primary diffusion direction, which are thought to reflect the neural bases of age differences in diffusion (i.e., axonal shrinkage and demyelination, respectively). In the present study, patterns of age differences in white matter integrity were assessed by comparing younger and healthy older adults on multiple measures of integrity (FA, AD, RD). Results revealed two commonly reported patterns (Radial Increase Only and Radial/Axial Increase), and one relatively novel pattern (Radial Increase/Axial Decrease) that varied by brain region and may reflect differential aging of microstructural (e.g., degree of myelination) and macrostructural (e.g., coherence of fiber orientation) properties of white matter. In addition, larger age differences in FA in frontal white matter were consistent with the anterior-posterior gradient of age differences in white matter integrity. Together, these findings complement other recent studies in providing information about patterns of diffusivity that are characteristic of healthy aging. KeywordsAging; axial diffusivity; DTI; fractional anisotropy; radial diffusivity Brain aging research has been dominated by examinations of age-related differences in the structure and function of gray matter (Cabeza, et al. 2005), with the other half of the brainwhite matter-having been largely ignored. The lack of attention to white matter aging in the past likely resulted from limitations in imaging technology, because the relatively recent Address correspondence to: Ilana J. Bennett, Georgetown University, Department of Psychology, 301 N White Gravenor Building, Washington, DC 20057, PH: 202-687-4099, FX: 202-687-6050, ijb5@georgetown.edu. Preliminary findings from this project were presented at the Society for Neuroscience Conferences in San Diego, CA in November, 2007 and Washington, DC in November, 2008; NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript advent of diffusion tensor imaging (DTI) has led to widespread in interest in age-related changes in white matter.DTI is a magnetic resonance imaging (MRI) technique that measures the diffusion of molecular water (Basser, et al. 1994;. Water diffuses 3-7 times more rapidly along the length of axons aligned in white matter tracts compared to movement perpendicular to the axons (Le Bihan 2003; because the latter is restricted by axonal cell membranes, myelin sheaths, and neurofilaments (Beaulieu 2002). Various properties of water diffusion can be calculated from DTI-based eigenvalue measures (λ1, λ2, and λ3; which indicate the rate of diffusion along the...

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

“…Since FA also declined with age in the genu and the ventromedial prefrontal WM with an increase of mean diffusivity (MD), axial diffusivity (AxD), and RD, this data supports the idea that the frontal cortex is particularly vulnerable to agerelated myelin loss (i.e., is age-sensitive; Michielse et al 2010). A number of studies, using similar techniques, have proposed that the timing and combination of agerelated changes in FA, MD, AxD, and RD may reflect a progression of mild to severe WM changes, including demyelination, axonal loss/damage, inflammation, and gliosis (Bennett et al 2010;Burzynska et al 2010;Sala et al 2010;Zhang et al 2010).…”

Mechanisms of white matter changes induced by meditation

“…In contrast to AD, which signifies axonal morphology, RD implicates the character of the myelin. Decrease in RD implies increased myelination, and increase represents demyelination (2,3,8). This evidence in human neuroimaging studies is consistent with animal studies examining axons and myelination histologically and comparing them directly with DTI results (12, 13).…”

“…Fractional anisotropy (FA) is an important index for measuring the integrity of white matter fibers. In general, a higher FA value has been related to improved performance, and reduced FA has been found in normal aging and in neurological or psychiatric disorders (1,(6)(7)(8).FA alterations originate from several factors, such as changes in myelination, axon density, axonal membrane integrity, axon diameter, and intravoxel coherence of fiber orientation and others changes (1, 9). To understand the mechanisms of FA change, several DTI studies have examined axial diffusivity (AD) and radial diffusivity (RD), the most important indices associated with FA (6-8).…”

“…Fractional anisotropy (FA) is an important index for measuring the integrity of white matter fibers. In general, a higher FA value has been related to improved performance, and reduced FA has been found in normal aging and in neurological or psychiatric disorders (1,(6)(7)(8).…”

Quantitative Tract-Specific Measures of Uncinate and Cingulum in Major Depression Using Diffusion Tensor Imaging

“…We also computed two additional measures including the axial diffusivity (the degree of water diffusion along the direction parallel to the fiber bundles) and radial diffusivity (water diffusion perpendicular to the axonal wall). These two measures provide more information on the relative diffusivity of water molecules beyond standard FA, and have been utilized to differentiate among various white matter microstructural changes (Song et al, 2003;Metwalli et al, 2010;Bennett et al, 2010). We hypothesized that white matter abnormalities will be present in the UF and CB tracts of MDD subjects when compared with healthy controls (HC).…”