Memantine and HIV-associated cognitive impairment: A neuropsychological and proton magnetic resonance spectroscopy study

Giovanni Schifitto, Bradford A. Navia, Constantin Yiannoutsos, Christina M. Marra, Linda Chang, Thomas Ernst, Jeffrey G. Jarvik, Eric N. Miller, Elyse J. Singer, Ronald J. Ellis, Dennis L. Kolson, David Simpson, Avindra Nath, Joseph Berger, Sharon L. Shriver, Linda L. Millar, Dodi Colquhoun, Robert Lenkinski, R. Gilberto Gonzalez, Stuart A. Lipton

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: To assess the safety and efficacy of memantine, an uncompetitive antagonist of the N-methyl-D-aspartate receptor as treatment of HIV-associated cognitive impairment. METHODS: This was a Phase II randomized, double-blind, placebo-controlled, multicenter trial within the Adult AIDS Clinical Trials Group. One-hundred and forty HIV-infected adults with mild to severe AIDS dementia complex receiving stable antiretroviral therapy were enrolled. Memantine was initiated at 10 mg daily escalated to 40 mg daily, or up to the maximum tolerated dose and continued for 16 weeks (primary evaluation visit) followed by a 4-week washout period and re-evaluation at week 20. Changes in cognitive performance were measured as percent change from baseline to week 16 in the average of eight neuropsychological test scores (NPZ-8). Brain metabolism was measured by magnetic resonance spectroscopy in a subgroup of subjects. RESULTS: Sixty-one percent of subjects in the memantine group and 85% in the placebo group reached the 40 mg dose while the reported adverse experiences between the two groups were similar. There were no significant improvements in neuropsychological performance over 16 weeks; however, memantine was associated with a significant increase at week 16 in the N-acetyl aspartate to creatine ratio, in the frontal white matter (P = 0.040) and parietal cortex (P = 0.023). CONCLUSIONS: Memantine was safe and tolerated by HIV-infected subjects with cognitive impairment. Although we observed no significant differences in cognitive performance, the magnetic resonance spectroscopy data suggest that memantine may ameliorate neuronal metabolism, an important step to stabilizing or preventing neuronal injury. These results underscore the need for longer studies to assess the full potential of neuroprotective agents.

Original languageEnglish
Pages (from-to)1877-1886
Number of pages10
JournalAIDS
Volume21
Issue number14
DOIs
StatePublished - Sep 2007

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Memantine
HIV
Magnetic Resonance Spectroscopy
Placebos
AIDS Dementia Complex
Parietal Lobe
Maximum Tolerated Dose
Creatine
Neuropsychological Tests
Neuroprotective Agents
N-Methyl-D-Aspartate Receptors
Multicenter Studies
Cognitive Dysfunction
Proton Magnetic Resonance Spectroscopy
Acquired Immunodeficiency Syndrome
Clinical Trials
Safety
Wounds and Injuries
Brain
Therapeutics

Keywords

  • AIDS
  • Dementia
  • HIV
  • HIV dementia
  • Memantine
  • Neuroimaging
  • Neuroprotection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Memantine and HIV-associated cognitive impairment : A neuropsychological and proton magnetic resonance spectroscopy study. / Schifitto, Giovanni; Navia, Bradford A.; Yiannoutsos, Constantin; Marra, Christina M.; Chang, Linda; Ernst, Thomas; Jarvik, Jeffrey G.; Miller, Eric N.; Singer, Elyse J.; Ellis, Ronald J.; Kolson, Dennis L.; Simpson, David; Nath, Avindra; Berger, Joseph; Shriver, Sharon L.; Millar, Linda L.; Colquhoun, Dodi; Lenkinski, Robert; Gonzalez, R. Gilberto; Lipton, Stuart A.

In: AIDS, Vol. 21, No. 14, 09.2007, p. 1877-1886.

Research output: Contribution to journalArticle

Schifitto, G, Navia, BA, Yiannoutsos, C, Marra, CM, Chang, L, Ernst, T, Jarvik, JG, Miller, EN, Singer, EJ, Ellis, RJ, Kolson, DL, Simpson, D, Nath, A, Berger, J, Shriver, SL, Millar, LL, Colquhoun, D, Lenkinski, R, Gonzalez, RG & Lipton, SA 2007, 'Memantine and HIV-associated cognitive impairment: A neuropsychological and proton magnetic resonance spectroscopy study', AIDS, vol. 21, no. 14, pp. 1877-1886. https://doi.org/10.1097/QAD.0b013e32813384e8
Schifitto, Giovanni ; Navia, Bradford A. ; Yiannoutsos, Constantin ; Marra, Christina M. ; Chang, Linda ; Ernst, Thomas ; Jarvik, Jeffrey G. ; Miller, Eric N. ; Singer, Elyse J. ; Ellis, Ronald J. ; Kolson, Dennis L. ; Simpson, David ; Nath, Avindra ; Berger, Joseph ; Shriver, Sharon L. ; Millar, Linda L. ; Colquhoun, Dodi ; Lenkinski, Robert ; Gonzalez, R. Gilberto ; Lipton, Stuart A. / Memantine and HIV-associated cognitive impairment : A neuropsychological and proton magnetic resonance spectroscopy study. In: AIDS. 2007 ; Vol. 21, No. 14. pp. 1877-1886.
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abstract = "OBJECTIVE: To assess the safety and efficacy of memantine, an uncompetitive antagonist of the N-methyl-D-aspartate receptor as treatment of HIV-associated cognitive impairment. METHODS: This was a Phase II randomized, double-blind, placebo-controlled, multicenter trial within the Adult AIDS Clinical Trials Group. One-hundred and forty HIV-infected adults with mild to severe AIDS dementia complex receiving stable antiretroviral therapy were enrolled. Memantine was initiated at 10 mg daily escalated to 40 mg daily, or up to the maximum tolerated dose and continued for 16 weeks (primary evaluation visit) followed by a 4-week washout period and re-evaluation at week 20. Changes in cognitive performance were measured as percent change from baseline to week 16 in the average of eight neuropsychological test scores (NPZ-8). Brain metabolism was measured by magnetic resonance spectroscopy in a subgroup of subjects. RESULTS: Sixty-one percent of subjects in the memantine group and 85{\%} in the placebo group reached the 40 mg dose while the reported adverse experiences between the two groups were similar. There were no significant improvements in neuropsychological performance over 16 weeks; however, memantine was associated with a significant increase at week 16 in the N-acetyl aspartate to creatine ratio, in the frontal white matter (P = 0.040) and parietal cortex (P = 0.023). CONCLUSIONS: Memantine was safe and tolerated by HIV-infected subjects with cognitive impairment. Although we observed no significant differences in cognitive performance, the magnetic resonance spectroscopy data suggest that memantine may ameliorate neuronal metabolism, an important step to stabilizing or preventing neuronal injury. These results underscore the need for longer studies to assess the full potential of neuroprotective agents.",
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T2 - A neuropsychological and proton magnetic resonance spectroscopy study

AU - Schifitto, Giovanni

AU - Navia, Bradford A.

AU - Yiannoutsos, Constantin

AU - Marra, Christina M.

AU - Chang, Linda

AU - Ernst, Thomas

AU - Jarvik, Jeffrey G.

AU - Miller, Eric N.

AU - Singer, Elyse J.

AU - Ellis, Ronald J.

AU - Kolson, Dennis L.

AU - Simpson, David

AU - Nath, Avindra

AU - Berger, Joseph

AU - Shriver, Sharon L.

AU - Millar, Linda L.

AU - Colquhoun, Dodi

AU - Lenkinski, Robert

AU - Gonzalez, R. Gilberto

AU - Lipton, Stuart A.

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N2 - OBJECTIVE: To assess the safety and efficacy of memantine, an uncompetitive antagonist of the N-methyl-D-aspartate receptor as treatment of HIV-associated cognitive impairment. METHODS: This was a Phase II randomized, double-blind, placebo-controlled, multicenter trial within the Adult AIDS Clinical Trials Group. One-hundred and forty HIV-infected adults with mild to severe AIDS dementia complex receiving stable antiretroviral therapy were enrolled. Memantine was initiated at 10 mg daily escalated to 40 mg daily, or up to the maximum tolerated dose and continued for 16 weeks (primary evaluation visit) followed by a 4-week washout period and re-evaluation at week 20. Changes in cognitive performance were measured as percent change from baseline to week 16 in the average of eight neuropsychological test scores (NPZ-8). Brain metabolism was measured by magnetic resonance spectroscopy in a subgroup of subjects. RESULTS: Sixty-one percent of subjects in the memantine group and 85% in the placebo group reached the 40 mg dose while the reported adverse experiences between the two groups were similar. There were no significant improvements in neuropsychological performance over 16 weeks; however, memantine was associated with a significant increase at week 16 in the N-acetyl aspartate to creatine ratio, in the frontal white matter (P = 0.040) and parietal cortex (P = 0.023). CONCLUSIONS: Memantine was safe and tolerated by HIV-infected subjects with cognitive impairment. Although we observed no significant differences in cognitive performance, the magnetic resonance spectroscopy data suggest that memantine may ameliorate neuronal metabolism, an important step to stabilizing or preventing neuronal injury. These results underscore the need for longer studies to assess the full potential of neuroprotective agents.

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