Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study.
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.
Schifitto
Giovanni
G
University of Rochester, Rochester, New York 14620, USA. giovanni.schifitto@ctcc.rochester.edu
Navia
Bradford A
BA
Yiannoutsos
Constantin T
CT
Marra
Christina M
CM
Chang
Linda
L
Ernst
Thomas
T
Jarvik
Jeffrey G
JG
Miller
Eric N
EN
Singer
Elyse J
EJ
Ellis
Ronald J
RJ
Kolson
Dennis L
DL
Simpson
David
D
Nath
Avindra
A
Berger
Joseph
J
Shriver
Sharon L
SL
Millar
Linda L
LL
Colquhoun
Dodi
D
Lenkinski
Robert
R
Gonzalez
R Gilberto
RG
Lipton
Stuart A
SA
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008559:Memantine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009483:Neuropsychological Tests; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents; D018691:Excitatory Amino Acid Antagonists; D012367:RNA, Viral; D008559:Memantine