Listed in Issue 235


DYSKEN and COLLEAGUES,  (1)Minneapolis VA Health Care System, Minneapolis, Minnesota; (2)James J. Peters VA Medical Research Center, New York, New York; (3)William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin; (4)Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico; (5)Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio6Case Western Reserve, University School of Medicine, Cleveland, Ohio; (6)Washington DC VA Medical Center, Washington, DC; (7)University of Pennsylvania School of Medicine, Philadelphia;

(8)Miami VA Healthcare System, Miami, Florida; (9)VA Maryland Healthcare System, Baltimore11University of Maryland Medical School, Department of Psychiatry, Baltimore.

(10)VA North Texas Health Care System, Dallas; (11)Ralph H. Johnson VA Medical Center, Charleston, South Carolina14Department of Health Studies, Medical University of South Carolina, Charleston 15 Roper St Francis Healthcare, Charleston, South Carolina; (12)VA Ann Arbor Healthcare System, Ann Arbor, Michigan; (13)VA Caribbean Healthcare System, San Juan, Puerto Rico; (14)Bay Pines VA Healthcare System, Bay Pines, Florida; (15)VA Boston Healthcare System, Boston, Massachusetts; (16)VA Puget Sound Health Care System, Seattle, Washington21Department of Psychiatry  and Behavioral Sciences, University of Washington, Seattle; (17)Iowa City VA Medical Center, Iowa City, Iowa23University of Iowa, Iowa City; (18)W. G. (Bill) Hefner VA Medical Center, Salisbury, North Carolina; (19)Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare System, West Haven, 26Yale University School of Public Health, New Haven, Connecticut sought to determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase  inhibitor


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. The authors sought 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.


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.


TRIAL REGISTRATION: Identifier: NCT00235716.

Dysken MW(1), Sano M(2), Asthana S(3), Vertrees JE(4), Pallaki M(5), Llorente  M(6), Love S(1), Schellenberg GD(7), McCarten JR(1), Malphurs J(8), Prieto S(8),   Chen P(5), Loreck DJ(9), Trapp G(10), Bakshi RS(10), Mintzer JE(11), Heidebrink  JL(12), Vidal-Cardona A(13), Arroyo LM(13), Cruz AR(14), Zachariah S(14), Kowall   NW(15), Chopra MP(15), Craft S(16), Thielke S(16), Turvey CL(17), Woodman C(17),   Monnell KA(18), Gordon K(18), Tomaska J(1), Segal Y(1), Peduzzi PN(19), Guarino  PD(19).  Effect of vitamin E and memantine on functional decline in Alzheimer disease: the  TEAM-AD VA cooperative randomized trial. JAMA. 311(1):33-44.  Jan 1 2014. doi: 10.1001/jama.2013.282834. Erratum in JAMA. 311(11):1161. Mar 19 2014.  Comment in  JAMA. 311(1):29-30. Jan 1 2014.    Evid Based Med. 19(4):140. Aug  2014.


Alzheimer’s Disease is now the No. 1 cause of death in the elderly; results and further research to progress the diagnosis and treatment and outcome is definitely a priority.

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