title: White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals.
abstract: Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4 = 529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.
authors.affiliation: San Diego State University/University of California, San Diego, Joint Doctoral Program in Clinical Psychology, San Diego and La Jolla, California, USA.
authors.forename: Assawin
authors.initials: A
authors.lastname: Gongvatana
authors.forename: Brian C
authors.initials: BC
authors.lastname: Schweinsburg
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Taylor
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Theilmann
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.forename: Omar M
authors.initials: OM
authors.lastname: Alhassoon
authors.forename: Joanna
authors.initials: J
authors.lastname: Jacobus
authors.forename: Steven P
authors.initials: SP
authors.lastname: Woods
authors.forename: Terry L
authors.initials: TL
authors.lastname: Jernigan
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Frank
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
mesh_terms: D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000209:etiology*; D000163:Acquired Immunodeficiency Syndrome / Q000134:cerebrospinal fluid / Q000150:complications* / Q000188:drug therapy*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000473:pathology; D020208:Brain Injury, Chronic / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000209:etiology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006678:HIV / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012367:RNA, Viral / Q000134:cerebrospinal fluid; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral