Regional neuropathology and cognitive abilities in HIV infection

The current study expanded previous work showing that antemortem neuropsychological (NP) impairment is an excellent indicator of postmortem neuropathology in HIV disease. One objective was to determine if NP impairment could better predict neurodegeneration (ND) by evaluating multiple markers of ND in multiple brain regions (midfrontal cortex, hippocampus, and putamen). Another objective was to determine if anticipated patterns of NP deficits were related to regional ND in the above brain regions. Twenty-seven cases with complete antemortem NP examinations and post-mortem neuropathological data were assessed. Laser Confocal Scanning Microscopy was used to determine the level of ND based on two markers: microtubule associated protein (MAP2; neuronal cell bodies and dendrites) and synaptophysin (SYN; presynaptic terminals). A multiple regression analysis using the three regional MAP2 measures as predictors of global NP ability was not significant; however, a similar model using regional SYN measures was significant (F_3,23 = 3.75, p = 0.02, R2 = 0.33). An “across-antibody regional neurodegeneration” (AARN) score, combining both MAP2 and SYN and emphasizing the severity of ND, was created for each brain region. A multiple regression model, using the three regional AARN scores as simultaneous predictors of global NP ability, was significant (F_3,23 = 6.17, p < 0.01, R2 = 0.45). Both the hippocampus and the putamen were significant contributors to this model. Additionally, AARN scores were significantly related to NP domain ratings of: executive functioning, processing speed, learning, and recall. ND of individual brain regions did not specifically relate to NP abilities as hypothesized. AARN scores from the midfrontal cortex and hippocampus were correlated with each other, and this relationship may have decreased specificity for regional patterns of NP impairment. The correlation between regional ND measures demonstrated that ND tends to be diffuse or “spotty” across multiple brain regions, and specific NP abilities may be dependent on the integrity of the whole neuronal network. This study found that the predictive utility of NP impairment is strengthened by evaluating multiple ND markers in multiple brain regions. Future treatment studies should focus on combating ND, as it appears to be critically linked to HIV-associated NP impairment.