HEALTH NEWS

Study Title:

Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease

Study Abstract

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.

From press release:

Difficulty with activities of daily living often affect Alzheimer's patients, which is estimated to affect as many as 5.1 million Americans. These issues are among the most taxing burdens of the disease for caregivers, which total about 5.4 million family members and friends. New research from the faculty of Icahn School of Medicine at Mount Sinai working with Veterans Administration Medical Centers suggests that alpha tocepherol, fat-soluble Vitamin E and antioxidant, may slow functional decline (problems with daily activities such as shopping, preparing meals, planning, and traveling) in patients with mild-to-moderate Alzheimer's disease and decrease caregiver burden. There was no added benefit for memory and cognitive testing with the vitamin.

The study is published online first in the Jan. 1 Journal of the American Medical Association.

"Since the cholinesterase inhibitors [galantamine, donepezil, rivastigmine], we have had very little to offer patients with mild-to-moderate dementia," said Mary Sano, PhD, trial co-investigator, and professor in the department of psychiatry, Icahn School of Medicine at Mount Sinai, and director of research at the James J. Peters Veteran's Administration Medical Center, Bronx, New York. "This trial showed that vitamin E delays progression of functional decline by 19% per year, which translates into 6.2 months benefit over placebo."

The finding is valuable because vitamin E is easy to purchase at local drugstores and it is also inexpensive. The clinical trial investigators believe it can be recommended as a treatment strategy, based on the double-blind randomized controlled trial.

The Veteran's Administration Cooperative Randomized Trial of Vitamin E and memantine in Alzheimer's Disease (TEAM-AD examined the effects of vitamin E 2,000 IU/d, 20 mg/d of memantine, the combination, or placebo on Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory Score. Cognitive, neuropsychiatric, functional, and caregiver measures were secondary outcomes. A group of 613 patients with mild to moderate Alzheimer's disease were in the study, which was launched in August 2007 and finished in September 2012 at 14 Veterans Affairs Medical Centers.

Dr. Sano previously led a study on vitamin E in patients with moderately severe Alzheimer's disease. She found that the vitamin slowed disease progression in this group of patients as well.

Study Information

Maurice W. Dysken, Mary Sano, Sanjay Asthana, Julia E. Vertrees, Muralidhar Pallaki, Maria Llorente, Susan Love, Gerard D. Schellenberg, J. Riley McCarten, Julie Malphurs, Susana Prieto, Peijun Chen, David J. Loreck, George Trapp, Rajbir S. Bakshi, et al.
Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease
JAMA
2014 January
Minneapolis VA Health Care System, Minneapolis, Minnesota, James J. Peters VA Medical Research Center, New York, New York, et al.