Patients with AIDS have specific patterns of brain damage in regions that control motor, language and sensory functions, according to a study of brain scans published on 10th October in the online version of The Proceedings of the National Academy of Sciences of the USA.
The study found that brain damage was linked to the degree of immune system deterioration in some areas and to defects in movement or thinking in others. However, the use of antiretroviral therapy did not seem to have a significant effect on the overall degree of damage to the brain.
Around 40% of patients with AIDS develop symptoms of brain damage, ranging from minor deficits in movement or thinking to HIV-associated dementia. HIV is thought to enter the brain early in infection by travelling within macrophages. However, the physical effects of HIV infection on the brain’s structure remain poorly understood, as few studies have been able to compare brain structure in patients with and without HIV or AIDS.
To assess the degree of brain damage in patients with AIDS, researchers from the University of California Los Angeles and the University of Pittsburgh scanned 40 participants’ brains using magnetic resonance imaging (MRI). Twenty-six of the participants had AIDS, defined as Centers for Disease Control and Prevention (CDC) stage C, while the remainder were HIV-negative but with similar ages and risk factors for HIV. None of the AIDS patients had dementia.
The investigators found that certain regions of the outer ‘cortex’ of the brain were 15% thinner in the AIDS patients. These included the brain’s sensory, motor, language and judgement centres.
“In AIDS patients without other brain infections, there is severe cortical thinning in primary sensorimotor, premotor and visual areas,” they write.
The investigators point out that these effects on the brain were observed despite 13 (50%) of the AIDS patients taking antiretroviral therapy and that the degree of cortical thinning was similar in the patients taking and not taking therapy.
“The use of highly active antiretroviral therapy is unlikely to mediate the severe pattern of cortical thinning seen here,” they conclude. However, the small sample size in this study may have prevented subtle differences from being detected. “Longitudinal data in larger samples are needed to fully address this question,” they write.
CD4 cell counts were associated with cortex thickness in two areas: the frontopolar cortex and the language cortex. This surprised the researchers, since damage to the immune system and the brain had been considered as separate phenomena previously.
In addition, they found that damage to the prefrontal cortex and the parietal cortex was linked to lower scores on measures of thinking and movement. “Cognitive impairment in AIDS was powerfully predicted by the level of atrophy in the prefrontal and parietal cortices,” the investigators write. This parallels the deficits observed in some patients with AIDS, including mild loss of vocabulary, problems with judgement and difficulty planning.
“The frontal cortical thinning observed here was strongly linked with cognitive impairment and may underlie the commonly observed HIV-related decline in frontal lobe functions such as attention, executive function, and working memory,” they explain. “These changes are strongly associated with HIV-related brain disease and independently predict diminished survival.”
The investigators argue that HIV could cause loss of brain cells by two mechanisms. Viral proteins such as Tat and gp120 are known to be toxic to brain cells, while the release of cytokines by HIV-infected macrophages could also damage the cells or the connections between them.
Thompson PM et al. Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proc Natl Acad Sci U S A, online edition, 2005.