Decreased brain dopamine transporters are related to cognitive deficits in HIV patients with or without cocaine abuse

Objective: Decreased dopamine transporters (DAT) in the basal ganglia were shown in patients with human immunodeficiency virus (HIV) associated dementia. Therefore, we assessed the relationship between striatal DAT and dopamine D2 receptors (D2R) availability and cognitive performance, and whether cocaine abuse, a common co-morbid condition in HIV patients, would be associated with further decreases in DAT and D2 receptors. Methods: 35 HIV-positive subjects [24 without (HIV) and 11 with a history of cocaine-dependence (HIV+Coc)] and 14 seronegative controls (SN) were evaluated with PET to measure DAT using [C-11]cocaine and D2R using [C-11]raclopride (availability of DAT or D2R estimated with Bmax/Kd), and a battery of neuropsychological tests. Results: Compared to SN controls, both HIV subject groups had lower DAT in putamen (HIV+Coc: - 16.7%, p = 0.003; HIV: - 12.2%, p = 0.02) and only HIV+Coc showed lower DAT in caudate (- 12.2%, p = 0.04). Lower D2R in both regions of both HIV groups were accounted by the greater nicotine use. Lower DAT, but not D2R, in putamen and caudate were associated with poorer performance on multiple neuropsychological tests, corrected for the effects of age, education, intelligence, mood, and nicotine use. Furthermore, a structural equation model (SEM) indicated that lower average dopamine function (both DAT and D2R) were related to poorer overall function on neuropsychological tests (p = 0.05). Interpretation: Reduced dopaminergic function may contribute to cognitive dysfunction in HIV patients with or without additional cocaine abuse. These findings suggest that these HIV patients may benefit from treatments that enhance dopamine function or protection from dopamine cell injury.