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Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer's disease
  1. Oscar L Lopez (lopezol{at}upmc.edu)
  1. University of Pittsburgh, United States
    1. James T Becker (beckerjt{at}upmc.edu)
    1. University of Pittsburgh, United States
      1. Abdus S Wahed (whaheda{at}edc.pitt.edu)
      1. University of Pittsburgh, United States
        1. Judith Saxton (saxtonja{at}upmc.edu)
        1. University of Pittsburgh, United States
          1. Robert A Sweet, Dr (sweetra{at}upmc.edu)
          1. University of Pittsburgh, United States
            1. David A Wolk (wolkda2{at}upmc.edu)
            1. University of Pittsburgh, United States
              1. William Klunk (klunkwe{at}upmc.edu)
              1. University of Pittsburgh, United States
                1. Steven T DeKosky (dekoskyst{at}upmc.edu)
                1. University of Pittsburgh, United States

                  Abstract

                  Background: Patients using cholinesterase inhibitors (ChEIs) have a delay in nursing home (NH) admission compared to 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’s 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 one-year follow-up evaluation. Of these patients, 140 (14.8%) used both ChEIs and memantine, 387 (45.0%) used only ChEIs, and 416 (40.1%) used neither. The mean follow-up time was 62.3 + 35.8 months. The analysis was conducted with multivariable Cox proportional hazard models controlling for critical covariates (i.e., age, education level, gender, severity of the dementia, hypertension, diabetes mellitus, heart disease, psychiatric symptoms, and use of psychotropic medications).

                  Results: Compared to those who never used cognitive enhancers, patients who used ChEIs had a significant delay in NH admission (HR: 0.37, 95%CI: 0.27 - 0.49); this effect was significantly augmented with the addition of memantine (HR: 0.29, 95%CI: 0.11 - 0.72) (memantine+ ChEI vs. ChEI alone). ChEIs alone, or in combination with memantine had no significant effect 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.

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