DEMENTIA AND HIV - NEUROPATHOLOGY

Cognitive disorders associated with HIV infection may be due to focal lesions (lymphoma, toxoplasmosis, progressive multifocal leukoencephal itis, etc.), metabolic encephalopathy (e.g. hepatic insufficiency) or psychiatric disorders (depression). . In the absence of such causes a << cognitive and motor syndrome associated with HIV infection >> has b een defined on clinical criteria (Working group of the American Academ y of Neurology, 1991). This syndrome is not consistently associated wi th any specific lesion. Neither the multifocal encephalitis of HIV or CMV infection nor the diffuse leukoencephalopathy associated with HIV are the only causes. The existence of a neocortical neuronal loss has been suggested by several retrospective studies, but our prospective s tudy has not shown cortical or subcortical atrophy. Measurement of neu ronal density in Brodmann's areas 4,9 and 40 has not revealed a signif icant loss either global, by layer, or by column. The only constant le sion was gliosis of the cortex and white matter. Neuronal loss, theref ore, is not indispensable to the occurence of cognitive disorders in A IDS. The mechanism of dementia migh be: - dysfunction of cortical neur ons (dendritic abnormalities, virus/neurotransmitter competition); - s ubcortical dyfunction, as suggested by the high density of microglial nodules in that region; - white matter lesions which could be due to a bnormalities in the blood-brain barrier. The expression of cell adhesi on molecules (VCAM-1, VLA-4, ICAM-1 and LFA-1) by endothelial cerebral cells is not significantly different in AIDS patients, demented or no t, and in patients with multiple sclerosis. In contrast, the expressio n of VCAM1- by astrocytes is significantly increased in demented AIDS patients compared with non demented ones. This finding opens new vista s for research in the mechanism of AIDS-associated dementia.