Cortical Atrophy and White Matter Hyperintensities in HIV: The Hawaii Aging with HIV Cohort Study

Abstract

Background-As many HIV seropositive individuals are now living longer after infection due to highly active antiretroviral therapy, aging related manifestations of cerebral small vessel ischemic vascular disease, such as brain white matter hyperintensities, are becoming increasingly important in this population.

A lipid storage–like disorder contributes to cognitive decline in HIV-infected subjects

“…8,9 Despite cART, there is evidence for ongoing neurologic damage that includes persistent astrocyte infection, brain volume loss, inflammation, synaptodendritic damage, and disruptions in white matter integrity. 5,[10][11][12] The mechanisms underlying these residual neuropathologic impairments remain obscure.…”

“…8,9 Despite cART, there is evidence for ongoing neurologic damage that includes persistent astrocyte infection, brain volume loss, inflammation, synaptodendritic damage, and disruptions in white matter integrity. 5,[10][11][12] The mechanisms underlying these residual neuropathologic impairments remain obscure.Several studies have suggested that dysregulations in CNS lipid metabolism may be involved in the pathogenesis of HAND. [13][14][15] In particular, roles for ceramides, sphingomyelins, and cholesterol have been described, but the interrelationships of these bioactive lipids to the temporal progression *These authors contributed equally to this work.…”

The Role of Medical Imaging in Defining CNS Abnormalities Associated with HIV-Infection and Opportunistic Infections

“…Reductions in cerebral cortex volume have been reported [13,15] and linked with total white matter hyperintensity (WMH) volume [27]. Analyzing cortical thickness, Thompson et al [28] found up to a 15% decrease in the cortical thickness of primary motor and sensory as well as premotor cortices in patients with acquired immune deficiency syndrome (AIDS) relative to controls.…”

“…Others have described localized white matter damage observed as signal intensities (i.e. WMHs) on T2-weighted or fluid attenuated inversion recovery (FLAIR) scans [13,27,33], although these findings have been contradicted [16] and shown to be unrelated to HIV biomarkers [27]. The mechanism underlying WMHs in HIV is not yet well understood as the pathological specificity of WMHs in structural imaging is not known in HIV; it has, however, been speculated that white matter injury may be secondary to gray matter damage [15].…”

“…The mechanism underlying WMHs in HIV is not yet well understood as the pathological specificity of WMHs in structural imaging is not known in HIV; it has, however, been speculated that white matter injury may be secondary to gray matter damage [15]. This hypothesis is supported by evidence that WMH volume in the frontal lobe is linked to frontal cortical atrophy [27]. One common theme expressed in these studies is the limitation of structural imaging in studying white matter injury, and many researchers have concluded that a more sensitive modality, such as DTI, may be more effective.…”