title: Vitamin E and memantine in Alzheimer's disease: clinical trial methods and baseline data.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: VA Minneapolis Health Care System, Minneapolis, MN, USA. Electronic address: maurice.dysken@va.gov.
authors.forename: Maurice W
authors.initials: MW
authors.lastname: Dysken
authors.affiliation: Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Guarino
authors.affiliation: VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, NM, USA.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Vertrees
authors.affiliation: William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
authors.affiliation: Bronx Veterans Medical Research Center, New York, NY, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.affiliation: VAMC, Washington, DC, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Llorente
authors.affiliation: Louis Stokes Cleveland VAMC, Cleveland, OH, USA.
authors.forename: Muralidhar
authors.initials: M
authors.lastname: Pallaki
authors.affiliation: VA Minneapolis Health Care System, Minneapolis, MN, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Love
authors.affiliation: University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
authors.affiliation: VA Minneapolis Health Care System, Minneapolis, MN, USA.
authors.forename: J Riley
authors.initials: JR
authors.lastname: McCarten
authors.affiliation: VA Miami Healthcare System, Miami, FL, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Malphurs
authors.affiliation: VA Miami Healthcare System, Miami, FL, USA.
authors.forename: Susana
authors.initials: S
authors.lastname: Prieto
authors.affiliation: Louis Stokes Cleveland VAMC, Cleveland, OH, USA.
authors.forename: Peijun
authors.initials: P
authors.lastname: Chen
authors.affiliation: VA Maryland Healthcare System, University of Maryland Medical School, Department of Psychiatry, Baltimore, MD, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Loreck
authors.affiliation: VA Maryland Healthcare System, Baltimore, MD, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Carney
authors.affiliation: VA North Texas Healthcare System, Dallas, TX, USA.
authors.forename: George
authors.initials: G
authors.lastname: Trapp
authors.affiliation: VA North Texas Healthcare System, Dallas, TX, USA.
authors.forename: Rajbir S
authors.initials: RS
authors.lastname: Bakshi
authors.affiliation: Ralph H. Johnson VAMC, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Jacobo E
authors.initials: JE
authors.lastname: Mintzer
authors.affiliation: VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
authors.forename: Judith L
authors.initials: JL
authors.lastname: Heidebrink
authors.affiliation: VA Caribbean Healthcare System, San Juan, PR.
authors.forename: Ana
authors.initials: A
authors.lastname: Vidal-Cardona
authors.affiliation: VA Caribbean Healthcare System, San Juan, PR.
authors.forename: Lillian M
authors.initials: LM
authors.lastname: Arroyo
authors.affiliation: Bay Pines VA Healthcare System, Bay Pines, FL, USA.
authors.forename: Angel R
authors.initials: AR
authors.lastname: Cruz
authors.affiliation: VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Neil W
authors.initials: NW
authors.lastname: Kowall
authors.affiliation: VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Mohit P
authors.initials: MP
authors.lastname: Chopra
authors.affiliation: VA Puget Sound Healthcare System, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craft
authors.affiliation: VA Puget Sound Healthcare System, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Thielke
authors.affiliation: Iowa City VAMC, University of Iowa, Iowa City, IA, USA.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Turvey
authors.affiliation: Iowa City VAMC, University of Iowa, Iowa City, IA, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Woodman
authors.affiliation: W.G. (Bill) Hefner VAMC, Salisbury, NC, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Monnell
authors.affiliation: W.G. (Bill) Hefner VAMC, Salisbury, NC, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Gordon
authors.affiliation: VA Minneapolis Health Care System, Minneapolis, MN, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Tomaska
authors.affiliation: VA Minneapolis Health Care System, Minneapolis, MN, USA.
authors.forename: Govind
authors.initials: G
authors.lastname: Vatassery
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D000975:Antioxidants / Q000627:therapeutic use*; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D014728:Veterans; D014810:Vitamin E / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D018691:Excitatory Amino Acid Antagonists; D014810:Vitamin E; D008559:Memantine
keywords: Alpha-tocopherol; Alzheimer's disease; Cholinesterase inhibitors; Memantine; Randomized trials; Vitamin E