Neurocognitive Complications of HIV Disease

Neurocognitive complications are the most common sequelae of HIV infection if the full spectrum of HIV disease—from initial seroconversion to death from advanced AIDS—is considered. Though resembling subcortical neurological disorders from a neuropsychological standpoint, the presentation is variable, and almost any pattern can be seen. Although neuropsychological impairment is often subtle, it can affect day-to-day life and is associated with earlier mortality. It is not clear if milder forms of neurocognitive disturbance necessarily presage advanced dementia, and current data suggest a two-factor model: a subacute relapsing-remitting condition that can occur at any stage of HIV disease and a progressive, more fulminant dementia. The pathological substrates of these conditions are not well characterized, although recent data support the notion that synaptodendritic damage underlies the neuropsychological impairment, and may precede the neuronal loss and other pathological features more characteristic of HIV encephalitis. Some reversibility of neurocognitive disturbance has been reported with zidovudine therapy, though the data are not consistent. New regimens involving protease inhibitors need to be evaluated in terms of benefit to the central nervous system because many drugs of this class do not penetrate the blood-brain barrier efficiently. Finally, studies utilizing experimental treatments that may affect the putative mechanisms of neural injury are in progress.