• aging;
  • Alzheimer's disease;
  • white matter;
  • prefrontal;
  • MRI;
  • DTI

Age-related degeneration of brain white matter (WM) has received a great deal of attention, with recent studies demonstrating that such changes are correlated with cognitive decline and increased risk for the development of age-related neurodegenerative disease. Past studies have used magnetic resonance imaging (MRI) to measure the volume of normal and abnormal tissue signal as an index of tissue pathology. More recently, diffusion tensor MRI (DTI) has been employed to obtain regional measures of tissue microstructure, such as fractional anisotropy (FA), providing better spatial resolution and potentially more sensitive metrics of tissue damage than traditional volumetric measures. We used DTI to examine the regional basis of age-related alterations in prefrontal WM. As expected from prior volumetric and DTI studies, prefrontal FA was reduced in older adults (OA) compared to young adults (YA). Although WM volume has been reported to be relatively preserved until late aging, FA was significantly reduced by middle age. Much of prefrontal WM showed reduced FA with increasing age. Ventromedial and deep prefrontal regions showed a somewhat greater reduction compared to other prefrontal areas. Prefrontal WM anisotropy correlated with prefrontal WM volume, but the correlation was significant only when the analysis was limited to participants over age 40. This evidence of widespread and regionally accelerated alterations in prefrontal WM with aging illustrates FA's potential as a microstructural index of volumetric measures.