Cortical and subcortical neurodegeneration is associated with HIV neurocognitive impairment

被引:161
作者
Moore, DJ
Masliah, E
Rippeth, JD
Gonzalez, R
Carey, CL
Cherner, M
Ellis, RJ
Achim, CL
Marcotte, RD
Heaton, RK
Grant, I
机构
[1] Univ Calif San Diego, Dept Psychiat, VA San Diego Healthcare Syst, La Jolla, CA 92161 USA
[2] HIV Neurobehav Res Ctr, La Jolla, CA USA
[3] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
[4] San Diego State Univ, Univ Calif San Diego, Joint Doctoral Program Clin Psychol, San Diego, CA 92182 USA
[5] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA
[6] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA
关键词
HIV infection; AIDS; cognition; neuropsychology; neurodegeneration;
D O I
10.1097/01.aids.0000218552.69834.00
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 [免疫学];
摘要
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 MAN individually. In a regression, hippocampal and putamen regional combined scores were independent predictors of degree of antemortem NP impairment (F-3,F-23=6.17; P<0.01; R-2=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. (C) 2006 Lippincott Williams & Wilkins.
引用
收藏
页码:879 / 887
页数:9
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