A close look at AIDS-related dementia raises questions that apply to other diseases as well. Dementia is found at increasing rates throughout the course of AIDS infection: from about 3 percent at the time that AIDS is first diagnosed to 8–16 percent of HIV-positive outpatients at a hospital clinic, to more than 60 percent of AIDS patients at the time of death. In theory, the prevalence of AIDS-related dementia could be even higher; some specialists estimate that the pathology that underlies it is present in 90 percent of terminal AIDS cases. This observation appears to point toward some form of slow dementia, which incubates over a period of 5 to 10 years and eventually affects cognitive function. Most long-term studies so far suggest that even if the brain is infected early, neuropsychological processes continue unimpaired up to a late stage.

The physical signs of disease in the brain that can be gleaned from medical imaging are also quite subtle up to a late stage of the disease, as reported by Richard T. Johnson, director of the neurology department at Johns Hopkins Medical School. Close examination of the tissues of the brain reveals some frayed white matter, often containing macrophages, and occasionally an abnormally large cell that appears to contain viral antigen, but in general no striking appearance of disease. The pathology is also evident in the spinal cord; here, one finds many macrophages, some demyelination, and, curiously, at the same time some remyelination or resheathing of nerve fibers. The virus itself is thought to reside largely in the macrophages and in microglia, cells that develop from macrophages and whose function in the brain is unclear.

The features of AIDS-related dementia actually correlate best with a demyelinating disease, and, in fact, demyelination has been observed to some degree. The means by which it comes about, however, are still unclear. One promising line of study focuses on cytokines, which, like antibodies, are a product of the immune system. It appears that the infection may induce a particular cytokine to attack the myelin sheaths; this possibility is under examination. Another question is whether the viral proteins, those contained in the macrophages, for example, are toxic to cells or are harmful because they block the access of neurotransmitters to cells. Another possibility is transactivation, in which a gene from the AIDS virus acts as the “on”

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