Axonal chronic injury in treatment-naïve HIV+ adults with asymptomatic neurocognitive impairment and its relationship with clinical variables and cognitive status

未接受治疗的 HIV 感染成人无症状神经认知障碍患者的轴突慢性损伤及其与临床变量和认知状态的关系

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Abstract

BACKGROUND: HIV is a neurotropic virus, and it can bring about neurodegeneration and may even result in cognitive impairments. The precise mechanism of HIV-associated white matter (WM) injury is unknown. The effects of multiple clinical contributors on WM impairments and the relationship between the WM alterations and cognitive performance merit further investigation. METHODS: Diffusion tensor imaging (DTI) was performed in 20 antiretroviral-naïve HIV-positive asymptomatic neurocognitive impairment (ANI) adults and 20 healthy volunteers. Whole-brain analysis of DTI metrics between groups was conducted by employing tract-based spatial statistics (TBSS), including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). DTI parameters were correlated with clinical variables (age, CD4(+) cell count, CD4(+)/CD8(+) ratio, plasma viral load and duration of HIV infection) and multiple cognitive tests by using multilinear regression analyses. RESULTS: DTI quantified diffusion alterations in the corpus callosum and corona radiata (MD increased significantly, P < 0.05) and chronic axonal injury in the corpus callosum, corona radiata, internal capsule, external capsule, posterior thalamic radiation, sagittal stratum, and superior longitudinal fasciculus (AD increased significantly, P < 0.05). The impairments in the corona radiata had significant correlations with the current CD4(+)/CD8(+) ratios. Increased MD or AD values in multiple white matter structures showed significant associations with many cognitive domain tests. CONCLUSIONS: WM impairments are present in neurologically asymptomatic HIV+ adults, periventricular WM (corpus callosum and corona radiata) are preferential occult injuries, which is associated with axonal chronic damage rather than demyelination. Axonopathy may exist before myelin injury. DTI-TBSS is helpful to explore the WM microstructure abnormalities and provide a new perspective for the investigation of the pathomechanism of HIV-associated WM injury.

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