Cortical and subcortical neurodegeneration is associated with HIV neurocognitive impairment.
OBJECTIVE
To determine the association of markers of regional neurodegeneration (ND) at autopsy to degree of neurocognitive impairment in persons with HIV.


METHODS
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.
Moore
David J
DJ
HIV Neurobehavioral Research Center and University of California, San Diego, California 92161, USA. djmoore@ucsd.edu
Masliah
Eliezer
E
Rippeth
Julie D
JD
Gonzalez
Raul
R
Carey
Catherine L
CL
Cherner
Mariana
M
Ellis
Ronald J
RJ
Achim
Cristian L
CL
Marcotte
Thomas D
TD
Heaton
Robert K
RK
Grant
Igor
I
D000328:Adult; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D003072:Cognition Disorders / Q000473:pathology / Q000821:virology*; D018450:Disease Progression; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000473:pathology / Q000523:psychology*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000523:psychology / Q000821:virology*; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011594:Psychometrics; D011699:Putamen / Q000473:pathology