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Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial


Dysken, Maurice W., Sano, Mary, Asthana, Sanjay, Vertrees, Julia E., Pallaki, Muralidhar, Llorente, Maria, Love, Susan, Schellenberg, Gerard D., McCarten, J. Riley, Malphurs, Julie, Prieto, Susana, Chen, Peijun, Loreck, David J., Trapp, George, Bakshi, Rajbir S., Mintzer, Jacobo E., Heidebrink, Judith L., Vidal-Cardona, Ana, Arroyo, Lillian M., Cruz, Angel R., Zachariah, Sally, Kowall, Neil W., Chopra, Mohit P., Craft, Suzanne, Thielke, Stephen, Turvey, Carolyn L., Woodman, Catherine, Monnell, Kimberly A., Gordon, Kimberly, Tomaska, Julie, Segal, Yoav, Peduzzi, Peter N., Guarino, Peter D.


JAMA, Volume: 311, No.: 1, Pages.: 33-44

Year of Publication



Importance: 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.; Objective: To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor.; Design, Setting, and Participants: 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.; Interventions: 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).; Main Outcomes and Measures: 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.; Results: 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).; Conclusions and Relevance: 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.; Trial Registration: Identifier: NCT00235716.;

Bibtex Citation

@article{Dysken_2014, doi = {10.1001/jama.2013.282834}, url = {}, year = 2014, month = {jan}, publisher = {American Medical Association ({AMA})}, volume = {311}, number = {1}, pages = {33}, author = {Maurice W. Dysken and Mary Sano and Sanjay Asthana and Julia E. Vertrees and Muralidhar Pallaki and Maria Llorente and Susan Love and Gerard D. Schellenberg and J. Riley McCarten and Julie Malphurs and Susana Prieto and Peijun Chen and David J. Loreck and George Trapp and Rajbir S. Bakshi and Jacobo E. Mintzer and Judith L. Heidebrink and Ana Vidal-Cardona and Lillian M. Arroyo and Angel R. Cruz and Sally Zachariah and Neil W. Kowall and Mohit P. Chopra and Suzanne Craft and Stephen Thielke and Carolyn L. Turvey and Catherine Woodman and Kimberly A. Monnell and Kimberly Gordon and Julie Tomaska and Yoav Segal and Peter N. Peduzzi and Peter D. Guarino}, title = {Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease}, journal = {{JAMA}} }


activities of daily living, adverse effects, aged, aged, 80 and over, alpha, alzheimer disease, antioxidants, caregivers, cholinesterase inhibitors, disease progression, dopamine agents, double-blind method, drug therapy, drug therapy combination, e, female, humans, male, memantine, middle aged, nursing, physiopathology, severity of illness index, therapeutic use, tocopherol, treatment outcome, vitamin, vitamin e

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes

ADLs/IADLs, Cognition, Service use or cost reductions (incl. hospital use reduction, care home admission delay)


Hospital Outpatient Care

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Anti-Alzheimer medications, e.g.: donezepil, galantamine, rivastigmine, memantime, Herbal remedies, vitamins, dietary supplements