Selegiline and oxidative stress in HIV-associated cognitive impairment.

TitleSelegiline and oxidative stress in HIV-associated cognitive impairment.
Publication TypeJournal Article
Year of Publication2009
AuthorsSchifitto G, Yiannoutsos CT, Ernst T, Navia BA, Nath A, Sacktor N, Anderson C, Marra CM, Clifford DB
Corporate AuthorsACTG 5114 Team
JournalNeurology
Volume73
Issue23
Pagination1975-81
Date Published2009 Dec 8
ISSN1526-632X
KeywordsAdult, AIDS Dementia Complex, Biomarkers, Pharmacological, Cognition Disorders, Female, HIV Infections, Humans, Male, Middle Aged, Oxidative Stress, Selegiline
Abstract

OBJECTIVE: To assess the effectiveness of the selegiline transdermal system (STS) in reversing HIV-induced metabolic brain injury (as measured by proton magnetic resonance spectroscopy [MRS]) and in decreasing oxidative stress, measured by CSF protein carbonyl concentration.

METHODS: Sixty-two subjects with HIV-associated cognitive impairment were coenrolled in a 24-week placebo-controlled study (AIDS Clinical Trial Group protocol A5090) and were randomly assigned to receive STS 3 mg/24 h, STS 6 mg/24 h, or matching placebo. Cognitive performance was evaluated using the neuropsychological z score (NPZ)-8 and NPZ-6, as well as cognitive domain scores. Subjects underwent proton MRS at study entry and weeks 12 and 24. CSF protein carbonyl was measured at baseline and week 24.

RESULTS: A slight increase in N-acetyl aspartate/creatine from baseline to week 24 was found in the basal ganglia (p = 0.023) and centrum semiovale (p = 0.072) of the placebo group compared with the STS groups; however, there were no significant changes when the absolute metabolite concentrations were analyzed. The levels of choline/creatine in the midfrontal cortex were also significantly higher during the week 12 visit in the combined STS groups. This persisted to the week 24 visit (p = 0.002). Evaluation of the change in NPZ-8, NPZ-6, and cognitive domain scores from baseline to weeks 12 and 24 revealed no significant differences between treatment arms. Protein carbonyl analysis revealed no significant changes among the groups.

CONCLUSION: In this 24-week study, the selegiline transdermal system (STS) had no effect on either magnetic resonance spectroscopy (MRS) metabolites or oxidative stress, as measured by CSF protein carbonyl concentration. The lack of effect on these biomarkers is also reflected in the lack of cognitive improvement in the STS groups compared to placebo.

LEVEL OF EVIDENCE: This study provides Class II evidence that STS had no effect on either MRS metabolites or oxidative stress, as measured by CSF protein carbonyl concentration over a period of 24 weeks.

DOI10.1212/WNL.0b013e3181c51a48
Alternate JournalNeurology
PubMed ID19890073
PubMed Central IDPMC2790227
Grant List2-P01 MH064570-05 / MH / NIMH NIH HHS / United States
5-M01 RR00044 / RR / NCRR NIH HHS / United States
5-P30-AI-045008-09 / AI / NIAID NIH HHS / United States
AI 069434 / AI / NIAID NIH HHS / United States
AI 69432 / AI / NIAID NIH HHS / United States
AI-069511-02 / AI / NIAID NIH HHS / United States
AI069465 / AI / NIAID NIH HHS / United States
AI27660 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
MH64409 / MH / NIMH NIH HHS / United States
NS32228 / NS / NINDS NIH HHS / United States
P30 MH075673 / MH / NIMH NIH HHS / United States
RR025005 / RR / NCRR NIH HHS / United States
U01-AI 032783-14 / AI / NIAID NIH HHS / United States