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Several studies have identified increased age as a risk factor for the development of cognitive impairment in human immunodeficiency virus (HIV)-infected subjects, but few have examined the potential synergistic effect of age and HIV serostatus on cognitive decline. The authors examined the possible combined effect of age and HIV serostatus on cognitive decline in 254 subjects stratified by age group and HIV status. After controlling for the effect of education, there were significant effects for serostatus and age group on overall cognitive impairment and a number of neuropsychological measures but no interaction effects. These data suggest that older seropositive individuals are not at an increased risk for HIV-related cognitive impairment when normal age-related cognitive changes are considered.

The effect of marijuana use on cognitive function is controversial. Although marijuana use is common in HIV-infected individuals for recreational and medicinal purposes, there have been no studies of the impact of marijuana on cognitive function in these subjects. Marijuana also has known immunologic effects, which increases the relevance in HIV-infected patients. We examined the interaction of HIV disease-stage and marijuana use in 282 subjects, stratified by disease stage and frequency of marijuana use. After controlling for the effects of depression, anxiety, and alcohol use, a significant interaction was observed on an overall measure of cognitive impairment. The effect of marijuana use was greatest in subjects with symptomatic HIV infection. Further inspection suggested that this effect was due primarily to performance on memory tasks. These data suggest that although there is minimal impact of marijuana on uninfected individuals or those at early stages of HIV infection, there is a synergistic effect of HIV and marijuana use in patients with advanced HIV disease. This is consistent with other data suggesting that the subtle effects of some conditions may become more manifest in the setting of immunocompromise.

Previous studies have demonstrated an impact of stress on immune function, and recent studies have suggested an adverse effect of stress on the brain. However, no previous study has examined the impact of stress on cognitive function. This article examines the relationship between stress and cognitive function in 82 HIV-negative subjects and 251 HIV-positive subjects. Subjects completed a comprehensive neuropsychological examination, measures of anxiety and depression, and a measure of stressful life events. After controlling for the impact of anxiety, depression, age, and education, stressful life events were related to cognitive impairment only among the HIV-positive subjects. The data were interpreted in the context of previous studies that have demonstrated an adverse effect of stress on the brain and suggest that this adverse impact may be expressed in the setting of a compromised immune system. Furthermore, this analysis suggests several implications for patient management.