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.
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.
Authors: David J Moore; Miguel Arce; Suzanne Moseley; J Allen McCutchan; Jennifer Marquie-Beck; Donald R Franklin; Florin Vaida; Cristian L Achim; Justin McArthur; Susan Morgello; David M Simpson; Benjamin B Gelman; Ann C Collier; Christina M Marra; David B Clifford; Robert K Heaton; Igor Grant Journal: J Neuropsychiatry Clin Neurosci Date: 2011 Impact factor: 2.198
Authors: Uraina S Clark; Ronald A Cohen; Lawrence H Sweet; Assawin Gongvatana; Kathryn N Devlin; George N Hana; Michelle L Westbrook; Richard C Mulligan; Beth A Jerskey; Tara L White; Bradford Navia; Karen T Tashima Journal: J Int Neuropsychol Soc Date: 2012-05-24 Impact factor: 2.892
Authors: Andrew J Levine; Susan Service; Eric N Miller; Sandra M Reynolds; Elyse J Singer; Paul Shapshak; Eileen M Martin; Ned Sacktor; James T Becker; Lisa P Jacobson; Paul Thompson; Nelson Freimer Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2012-05-24 Impact factor: 3.568
Authors: Sheila M Adams; Marina V Aksenova; Michael Y Aksenov; Charles F Mactutus; Rosemarie M Booze Journal: Synapse Date: 2010-11 Impact factor: 2.562
Authors: Mariana Cherner; Chad Bousman; Ian Everall; Daniel Barron; Scott Letendre; Florin Vaida; J Hampton Atkinson; Robert Heaton; Igor Grant Journal: J Int Neuropsychol Soc Date: 2010-08-23 Impact factor: 2.892
Authors: I Everall; F Vaida; N Khanlou; D Lazzaretto; C Achim; S Letendre; D Moore; R Ellis; M Cherner; B Gelman; S Morgello; E Singer; I Grant; E Masliah Journal: J Neurovirol Date: 2009-09 Impact factor: 2.643