Journal article
Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial
JAMA : the journal of the American Medical Association, Vol.311(1), pp.33-44
01/01/2014
DOI: 10.1001/jama.2013.282834
PMCID: PMC4109898
PMID: 24381967
Abstract
Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD.
To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor.
Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers.
Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152).
Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures.
Data from 561 participants were analyzed (alpha tocopherol = 140, memantine = 142, combination = 139, placebo = 140), with 52 excluded because of a lack of any follow-up data. Over the mean (SD) follow-up of 2.27 (1.22) years, ADCS-ADL Inventory scores declined by 3.15 units (95% CI, 0.92 to 5.39; adjusted P = .03) less in the alpha tocopherol group compared with the placebo group. In the memantine group, these scores declined 1.98 units less (95% CI, -0.24 to 4.20; adjusted P = .40) than the placebo group's decline. This change in the alpha tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period. Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations," with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants).
Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden.
clinicaltrials.gov Identifier: NCT00235716.
Details
- Title: Subtitle
- Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial
- Creators
- Maurice W Dysken - Minneapolis VA Health Care SystemMary Sano - James J. Peters VA Medical Research Center, New York, New YorkSanjay Asthana - Veterans Health AdministrationJulia E Vertrees - University of New MexicoMuralidhar Pallaki - Case Western Reserve UniversityMaria Llorente - United States Department of Veterans AffairsSusan Love - Minneapolis VA Health Care SystemGerard D Schellenberg - University of PennsylvaniaJ Riley McCarten - Minneapolis VA Health Care SystemJulie Malphurs - Veterans Health AdministrationSusana Prieto - Veterans Health AdministrationPeijun Chen - Case Western Reserve UniversityDavid J Loreck - University of Maryland, BaltimoreGeorge Trapp - VA North Texas Health Care SystemRajbir S Bakshi - VA North Texas Health Care SystemJacobo E Mintzer - United States Department of Veterans AffairsJudith L Heidebrink - VA Ann Arbor Healthcare SystemAna Vidal-Cardona - United States Department of Veterans AffairsLillian M Arroyo - United States Department of Veterans AffairsAngel R Cruz - Veterans Health AdministrationSally Zachariah - Veterans Health AdministrationNeil W Kowall - Veterans Health AdministrationMohit P Chopra - Veterans Health AdministrationSuzanne Craft - University of WashingtonStephen Thielke - University of WashingtonCarolyn L Turvey - Veterans Health AdministrationCatherine Woodman - University of IowaKimberly A Monnell - Veterans Health AdministrationKimberly Gordon - Veterans Health AdministrationJulie Tomaska - Minneapolis VA Health Care SystemYoav Segal - Minneapolis VA Health Care SystemPeter N Peduzzi - Yale UniversityPeter D Guarino - Veterans Health Administration
- Resource Type
- Journal article
- Publication Details
- JAMA : the journal of the American Medical Association, Vol.311(1), pp.33-44
- DOI
- 10.1001/jama.2013.282834
- PMID
- 24381967
- PMCID
- PMC4109898
- ISSN
- 0098-7484
- eISSN
- 1538-3598
- Grant note
- P50 AG005136 / NIA NIH HHS P50 AG005138 / NIA NIH HHS P30 AG013846 / NIA NIH HHS
- Language
- English
- Date published
- 01/01/2014
- Academic Unit
- Psychiatry; Epidemiology; Family and Community Medicine
- Record Identifier
- 9984281752202771
Metrics
15 Record Views