HIV-1
infection is characterized by multiple neurological syndromes occurring 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.