Brain Volumetric Alterations in Preclinical HIV-Associated Neurocognitive Disorder Using Automatic Brain Quantification and Segmentation Tool

Ruili Li,Wei Wang,Hongjun Li,Lin Shi,Zengxin Jiao,Aidong Zhang,Wing Kit Kung,Longjiang Zhang,Yu Qi,Yishan Luo,Guangxue Liu

doi:10.3389/fnins.2021.713760

Abstract

PurposeThis study aimed to determine if people living with HIV (PLWH) in preclinical human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND), with no clinical symptoms and without decreased daily functioning, suffer from brain volumetric alterations and its patterns.MethodFifty-nine male PLWH at the HAND preclinical stage were evaluated, including 19 subjects with asymptomatic neurocognitive impairment (ANI), 17 subjects with cognitive abnormality that does not reach ANI (Not reach ANI), and 23 subjects with cognitive integrity. Moreover, 23 healthy volunteers were set as the seronegative normal controls (NCs). These individuals underwent sagittal three-dimensional T1-weighted imaging (3D T1WI). Quantified data and volumetric measures of brain structures were automatically segmented and extracted using AccuBrain®. In addition, the multiple linear regression analysis was performed to analyze the relationship of volumes of brain structures and clinical variables in preclinical HAND, and the correlations of the brain volume parameters with different cognitive function states were assessed by Pearson’s correlation analysis.ResultsThe significant difference was shown in the relative volumes of the ventricular system, bilateral lateral ventricle, thalamus, caudate, and left parietal lobe gray matter between the preclinical HAND and NCs. Furthermore, the relative volumes of the bilateral thalamus in preclinical HAND were negatively correlated with attention/working memory (left: r = −0.271, p = 0.042; right: r = −0.273, p = 0.040). Higher age was associated with increased relative volumes of the bilateral lateral ventricle and ventricular system and reduced relative volumes of the left thalamus and parietal lobe gray matter. The lower CD4+/CD8+ ratio was associated with increased relative volumes of the left lateral ventricle and ventricular system. Longer disease course was associated with increased relative volumes of the bilateral thalamus. No significant difference was found among preclinical HAND subgroups in all indices, and the difference between the individual groups (Not reach ANI and Cognitive integrity groups) and NCs was also insignificant. However, there was a significant difference between ANI and NCs in the relative volumes of the bilateral caudate and lateral ventricle.ConclusionMale PLWH at the HAND preclinical stage suffer from brain volumetric alterations. AccuBrain® provides potential value in evaluating HIV-related neurocognitive dysfunction.

Highlights

Human immunodeficiency virus (HIV) can penetrate the central nervous system (CNS) after seroconversion at the initial stage of infection, subsequently leading to varying degrees of cognitive impairment, which is defined as HIVassociated neurocognitive disorder (HAND) (Antinori et al, 2007)
The innovation of our study is to focus on the preclinical stage of HAND and to subgroup the preclinical HAND according to the degree of cognitive impairment, to capture the dynamic changes of brain structure in preclinical stage
Fifty-nine participants met the criteria for preclinical HAND, including 19 asymptomatic neurocognitive impairment (ANI), 17 Not reach ANI, and 23 Cognitive integrity

Summary

Introduction

Human immunodeficiency virus (HIV) can penetrate the central nervous system (CNS) after seroconversion at the initial stage of infection, subsequently leading to varying degrees of cognitive impairment, which is defined as HIVassociated neurocognitive disorder (HAND) (Antinori et al, 2007). The progression of HIV-related cognitive impairment has been changed, which are manifested as the fact that HAND is characterized by HAD in the pre-cART era, while ANI is the majority in HAND in the post-cART era (Simioni et al, 2010). In the post-cART era, some PLWH present cognitive impairment in only one domain For these patients, their cognitive function has abnormalities that do not reach the level of ANI. The prevalence and impact of the preclinical HAND on PLWH gain importance gradually, and several guidelines have suggested screening all PLWH for HAND (Mind Exchange Working Group, 2013; British HIV Association, 2018; European AIDS Clinical Society, 2019)

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