HIV-1 Associated Dementia: Clinical Features and Pathogenesis

HIV-1 infection is characterized by multiple neurological syndromes occuring at all stages of infection. HIV-1-associated dementia, however, is the most devastating CNS consequence of AIDS because of its poor prognosis and functional impairment. A clinical triad of progressive cognitive decline, motor dysfunction, and behavioural abnormalities typifies this subcortical dementia which eventually affects 15 to 20% of AIDS patients. Neuroimaging, CSF studies and neuropsychological testing are frequently required in diagnosing HIV-associated dementia, to exclude other conditions including psychiatric illnesses, opportunistic diseases and systemic disorders. The pathogenesis of HIV dementia is uncertain and there is evidence that multiple mechanisms of neurological injury occur. These mechanisms include: the role of neurovirulent strains of HIV; the potential neurotoxicity of HIV gp120, nitric oxide and quinolinic acid; immunologically mediated CNS injury through the action of cytokines and arachidonic acid metabolites; and altered blood-brain barrier permeability. A collective approach involving clinical studies, in vitro assays and animal models will provide greater insight into the pathogenesis and the rational development of therapy for HIV dementia.