Selegiline and oxidative stress in HIV-associated cognitive impairment

G. Schifitto, Constantin Yiannoutsos, T. Ernst, B. A. Navia, A. Nath, N. Sacktor, C. Anderson, C. M. Marra, D. B. Clifford

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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.

Original languageEnglish
Pages (from-to)1975-1981
Number of pages7
JournalNeurology
Volume73
Issue number23
DOIs
StatePublished - Dec 2009

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Selegiline
Oxidative Stress
HIV
Placebos
Creatine
Proteins
Magnetic Resonance Spectroscopy
Cognitive Dysfunction
Clinical Protocols
Choline
Basal Ganglia
Brain Injuries
Acquired Immunodeficiency Syndrome
Biomarkers
Clinical Trials

ASJC Scopus subject areas

  • Clinical Neurology

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Schifitto, G., Yiannoutsos, C., Ernst, T., Navia, B. A., Nath, A., Sacktor, N., ... Clifford, D. B. (2009). Selegiline and oxidative stress in HIV-associated cognitive impairment. Neurology, 73(23), 1975-1981. https://doi.org/10.1212/WNL.0b013e3181c51a48

Selegiline and oxidative stress in HIV-associated cognitive impairment. / Schifitto, G.; Yiannoutsos, Constantin; Ernst, T.; Navia, B. A.; Nath, A.; Sacktor, N.; Anderson, C.; Marra, C. M.; Clifford, D. B.

In: Neurology, Vol. 73, No. 23, 12.2009, p. 1975-1981.

Research output: Contribution to journalArticle

Schifitto, G, Yiannoutsos, C, Ernst, T, Navia, BA, Nath, A, Sacktor, N, Anderson, C, Marra, CM & Clifford, DB 2009, 'Selegiline and oxidative stress in HIV-associated cognitive impairment', Neurology, vol. 73, no. 23, pp. 1975-1981. https://doi.org/10.1212/WNL.0b013e3181c51a48
Schifitto, G. ; Yiannoutsos, Constantin ; Ernst, T. ; Navia, B. A. ; Nath, A. ; Sacktor, N. ; Anderson, C. ; Marra, C. M. ; Clifford, D. B. / Selegiline and oxidative stress in HIV-associated cognitive impairment. In: Neurology. 2009 ; Vol. 73, No. 23. pp. 1975-1981.
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AU - Anderson, C.

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N2 - 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.

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