Diffusion tensor imaging (DTI) is an emerging technique combining magnetic resonance imaging (MRI) diffusion-weighted pulse sequences with tensor mathematics to encode molecular diffusion in 3-dimensions. Microstructural white matter integrity is known to decrease with increasing age, as well as with HIV-infection. Healthy aging and HIV-infection are associated with a pattern of cognitive deficits that are remarkably similar. Microstructural white matter changes may account for these changes, although the specific relationship to HIV-infection and aging remains to be evaluated. This study is designed to characterize the nature and extent of microstructural white matter disease associated with aging and HIV-1 infection and to clarify the association between the identified white matter changes associated with HIV-infection and healthy aging to concurrent neurocognitive performance. We will employ a four group, naturalistic design (30 young HIV-seropositive subjects, 30 older seropositive subjects, 30 young healthy controls, and 30 healthy older controls). In addition to completing a battery of cognitive tests known to be sensitive to frontal lobe and corpus callosal function, subjects will receive MRI and high resolution DTI scans evaluating both whole brain white matter and specific areas of interest (frontal forceps and corpus callosum). We will test the interactive and simple effects of HIV-infection and aging on structure and function with the following aims:
Aim 1 : To examine the relationship of aging and HIV-1 infection on white matter microstructural integrity. This will be accomplished by employing high-resolution diffusion tensor magnetic resonance imaging to evaluate subtle white matter disease through both whole brain analysis and the evaluation of specific regions of interest (frontal forceps and corpus callosum).
Aim 2 : To evaluate the relationship of aging, HIV-1 infection, and cognitive behaviors associated with frontal lobe functioning. This will be accomplished by comparing group performance on a number of neuropsychological measures of putative frontal lobe function.
Aim 3 : To examine the regional relationship between measures of frontal lobe function and interhemispheric transfer and microstructural white matter integrity. This will be accomplished by relating markers of white matter microstructure (fractional anisotropy and mean diffusivity) to concurrent neurocognitive performance.
| Smith, Clifford A; Stebbins, Glenn T; Bartt, Russell E et al. (2008) White matter anisotropy and depression symptoms in patients with HIV. J Neuropsychiatry Clin Neurosci 20:458-65 |
| Stebbins, Glenn T; Smith, Clifford A; Bartt, Russell E et al. (2007) HIV-associated alterations in normal-appearing white matter: a voxel-wise diffusion tensor imaging study. J Acquir Immune Defic Syndr 46:564-73 |
