Publication Abstract Display
Type: Published Manuscript
Title: Cortical and subcortical neurodegeneration is associated with HIV neurocognitive impairment.
Authors: Moore DJ, Masliah E, Rippeth JD, Gonzalez R, Carey CL, Cherner M, Ellis RJ, Achim CL, Marcotte TD, Heaton RK, Grant I, and the HNRC Group
Contact: HIV Neurobehavioral Research Center and University of California, San Diego, California 92161, USA.
Year: 2006
Publication: AIDS (London, England)
Volume: 20 Issue: 6 Pages: 879-87
Abstract:OBJECTIVE: To determine the association of markers of regional neurodegeneration (ND) at autopsy to degree of neurocognitive impairment in persons with HIV. DESIGN: In a prospectively followed cohort of HIV-infected individuals we examined the relationship between antemortem neuropsychological (NP) abilities and postmortem neuropathological data. METHODS: Twenty-seven HIV-infected individuals with both neuropsychological and neuropathological data were identified. Laser confocal scanning microscopy was used to determine the degree of ND based on: (1) microtubule-associated protein (MAP2; reflecting neuronal cell bodies and dendrites) and (2) synaptophysin (SYN; a measure of presynaptic terminals). A regional combined score, based on the distribution of percentage neuropil occupied by MAP2 and SYN and emphasizing severity of ND, was created for each brain region: midfrontal cortex, hippocampus, and putamen. RESULTS: The regional combined scores from each brain region studied were better correlated with level of global NP impairment than measures of SYN and MAP2 individually. In a regression, hippocampal and putamen regional combined scores were independent predictors of degree of antemortem NP impairment (F(3,23) = 6.17; P < 0.01; R2 = 0.45). The correlations among regional ND measures demonstrated that ND is unevenly distributed across multiple brain regions. CONCLUSIONS: As the anatomic distribution and temporal progression of neuropathologic changes appears to differ across individuals, it is important to consider both cortical and subcortical brain regions in studies of neuropathogenesis and treatment of HIV-related brain disease. Furthermore, combining information from several markers of neural injury provided the strongest association with degree of neurocognitive impairment during life.
Funding: NIDA:DA P01DA12065, NIMH:MH P30MH62512, NIMH:MH R24MH59745
Keywords: Adult, Brain, Cerebral Cortex, Cognition Disorders, Disease Progression, Follow-Up Studies, HIV Infections, Hippocampus, Humans, Male, Microscopy, Confocal, Middle Aged, Neurodegenerative Diseases, Neuropsychological Tests, Prospective Studies, Psychometrics, Putamen, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov''t

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