Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease
- O L Lopez1,2,3,
- J T Becker1,2,3,4,
- A S Wahed5,
- J Saxton1,2,3,
- R A Sweet1,2,3,6,
- D A Wolk1,3,
- W Klunk1,2,3,
- S T DeKosky1,2,3
- 1Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- 2Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- 3Alzheimer’s Disease Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- 4Department of Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- 5Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- 6VISN 4 Mental Illness Research Education and Clinical Center (MIRECC), VA Pittsburgh Health Care System, Pittsburgh, Pennsylvania, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Dr O L Lopez, 3501 Forbers Avenue, Oxford Building, Suite 830, Pittsburgh, PA 15213, USA; lopezol{at}upmc.edu
- Received 22 July 2008
- Revised 27 November 2008
- Accepted 3 December 2008
- Published Online First 9 February 2009
Abstract
Background: Patients using cholinesterase inhibitors (ChEIs) have a delay in nursing home (NH) admission compared with those who were not using the medication. There are no long-term studies of the effects of memantine in combination with ChEIs use in Alzheimer disease (AD). This study was conducted to examine the effects of ChEIs and memantine on time to death and time to NH admission.
Methods: Time to NH admission and death was examined in 943 probable AD patients who had at least a 1-year follow-up evaluation. Of these patients, 140 (14.9%) used both ChEIs and memantine, 387 (45.0%) used only ChEIs, and 416 (40.1%) used neither. The mean (SD) follow-up time was 62.3 (35.8) months. The analysis was conducted with multivariable Cox proportional hazard models controlling for critical covariates (ie, age, education level, gender, severity of the dementia, hypertension, diabetes mellitus, heart disease, psychiatric symptoms and use of psychotropic medications).
Results: Compared with those who never used cognitive enhancers, patients who used ChEIs had a significant delay in NH admission (HR: 0.37, 95% CI 0.27 to 0.49); this effect was significantly augmented with the addition of memantine (HR: 0.29, 95% CI 0.11 to 0.72) (memantine+ChEI vs ChEI alone). ChEIs alone, or in combination with memantine had no significant association on time to death.
Conclusions: This observational study revealed that the addition of the NMDA receptor antagonist memantine to the treatment of AD with ChEI significantly altered the treated history of AD by extending time to nursing home admission.
Footnotes
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Funding: This study was fully supported by grants AG03705, AG05133, AG16976, AG20098 and AG027224 from the National Institute on Aging, and by VISN 4 Mental Illness Research Education and Clinical Center (MIRECC), VA Pittsburgh Health Care System, Pittsburgh, Pennsylvania.
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Competing interests: None.
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Ethics approval: Ethics approval was provided by the University of Pittsburgh Institutional Review Board.
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Patient consent: Obtained.
