RESUMO
Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV- controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV- controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.
Assuntos
Substituição de Aminoácidos , Imagem de Tensor de Difusão/métodos , Infecções por HIV/diagnóstico por imagem , HIV/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Adulto , Mapeamento Encefálico , Estudos de Casos e Controles , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/patologia , Núcleo Caudado/virologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Corpo Caloso/virologia , Imagem de Tensor de Difusão/instrumentação , Feminino , Expressão Gênica , Variação Genética , Genótipo , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/virologia , HIV/patogenicidade , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Putamen/diagnóstico por imagem , Putamen/patologia , Putamen/virologia , Tálamo/diagnóstico por imagem , Tálamo/patologia , Tálamo/virologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/virologiaRESUMO
OBJECTIVE: To investigate the relationship between older age and mean cerebral white matter fiber bundle lengths (FBLs) in specific white matter tracts in the brain using quantified diffusion MRI. METHODS: Sixty-three healthy adults older than 50 years underwent diffusion tensor imaging. Tractography tracings of cerebral white matter fiber bundles were derived from the diffusion tensor imaging data. RESULTS: Results revealed significantly shorter FBLs in the anterior thalamic radiation for every 1-year increase over the age of 50 years. CONCLUSIONS: We investigated the effects of age on FBL in specific white matter tracts in the brains of healthy older individuals utilizing quantified diffusion MRI. The results revealed a significant inverse relationship between age and FBL. Longitudinal studies of FBL across a lifespan are needed to examine the specific changes to the integrity of white matter.