Send to:

Choose Destination
See comment in PubMed Commons below
Alzheimers Dement. 2014 Jan;10(1):36-44. doi: 10.1016/j.jalz.2013.01.014. Epub 2013 Apr 11.

Vitamin E and memantine in Alzheimer's disease: clinical trial methods and baseline data.

Author information

  • 1VA Minneapolis Health Care System, Minneapolis, MN, USA. Electronic address:
  • 2Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare System, West Haven, CT, USA.
  • 3VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, NM, USA.
  • 4William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
  • 5Bronx Veterans Medical Research Center, New York, NY, USA.
  • 6VAMC, Washington, DC, USA.
  • 7Louis Stokes Cleveland VAMC, Cleveland, OH, USA.
  • 8VA Minneapolis Health Care System, Minneapolis, MN, USA.
  • 9University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
  • 10VA Miami Healthcare System, Miami, FL, USA.
  • 11VA Maryland Healthcare System, University of Maryland Medical School, Department of Psychiatry, Baltimore, MD, USA.
  • 12VA Maryland Healthcare System, Baltimore, MD, USA.
  • 13VA North Texas Healthcare System, Dallas, TX, USA.
  • 14Ralph H. Johnson VAMC, Medical University of South Carolina, Charleston, SC, USA.
  • 15VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
  • 16VA Caribbean Healthcare System, San Juan, PR.
  • 17Bay Pines VA Healthcare System, Bay Pines, FL, USA.
  • 18VA Boston Healthcare System, Boston, MA, USA.
  • 19VA Puget Sound Healthcare System, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
  • 20Iowa City VAMC, University of Iowa, Iowa City, IA, USA.
  • 21W.G. (Bill) Hefner VAMC, Salisbury, NC, USA.



Alzheimer's disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha-tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N-methyl-D-aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD.


The Veterans Affairs Cooperative Studies Program initiated a multicenter, randomized, double-blind, placebo-controlled trial in August 2007, with enrollment through March 2012 and follow-up continuing through September 2012. Participants with mild-to-moderate AD who were taking an acetylcholinesterase inhibitor were assigned randomly to 2000 IU/day of alpha-tocopherol, 20 mg/day memantine, 2000 IU/day alpha-tocopherol plus 20 mg/day memantine, or placebo. The primary outcome for the study is the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory. Secondary outcome measures include the Mini-Mental State Examination; the Alzheimer's Disease Assessment Scale, cognitive portion; the Dependence Scale; the Neuropsychiatric Inventory; and the Caregiver Activity Survey. Patient follow-up ranged from 6 months to 4 years.


A total of 613 participants were randomized. The majority of the patients were male (97%) and white (86%), with a mean age of 79 years. The mean Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory score at entry was 57 and the mean Mini-Mental State Examination score at entry was 21.


This large multicenter trial will address the unanswered question of the long-term safety and effectiveness of alpha-tocopherol, memantine, and their combination in patients with mild-to-moderate AD taking an acetylcholinesterase inhibitor. The results are expected in early 2013.

Published by Elsevier Inc.


Alpha-tocopherol; Alzheimer's disease; Cholinesterase inhibitors; Memantine; Randomized trials; Vitamin E

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk