Diffusion tensor imaging of frontal white matter microstructure in early Alzheimer's disease: a preliminary study

Several investigators have suggested that the pathological progression of Alzheimer's disease appears to recapitulate the developmental maturation pattern, a process termed retrogenesis. Diffusion tensor imaging was used to test the hypothesis that the microstructural integrity of superior frontal and temporal white matter, one of the last regions to mature, would be reduced in vivo in early Alzheimer's disease. Five consecutive slices, from the orbitofrontal to periventricular frontal regions, as well as temporal and corpus callosal white matter regions, were sampled. Fractional anisotropy, mean diffusivity, axial diffusion, and radial diffusion of 10 patients with early Alzheimer's disease and 10 age-similar healthy control subjects were compared. Patients with Alzheimer's disease were found to have significantly reduced fractional anisotropy, increased mean diffusivity, and increased radial diffusion in superior frontal white matter. These data suggest that the integrity of periventricular frontal white matter rather than orbitofrontal white matter appears to be altered in early Alzheimer's disease and that the white matter abnormalities involve compromised myelin, consistent with the retrogenesis theory.