VA Study: Vitamin E ‘Significantly’ Slows Alzheimer’s Disease Functional Decline

by U.S. Medicine

February 5, 2014

By Brenda L. Mooney

Maurice W. Dysken, MD

Maurice W. Dysken, MD

MINNEAPOLIS — Could a vitamin found on drugstore shelves be effective in slowing cognitive decline for patients with Alzheimer’s disease?

New VA research found that a daily dose of 2,000 IUs of vitamin E slowed functional decline in patients with mild to moderate Alzheimer’s disease without significantly increasing mortality rates in the treatment group.

The `Veteran’s Administration Cooperative Randomized Trial of Vitamin E and memantine in Alzheimer’s disease (TEAM-AD)` study, led by Maurice W. Dysken, MD of the Minneapolis VA Health Care System and appearing recently in the Journal of the American Medical Association, involved 613 patients at 14 VA centers.1

“The main finding was that vitamin E slowed significantly the rate of progression for patients with mild-to-moderate Alzheimer’s disease over the average period of the study, which was a little over two years, compared to placebo, and that slowing represented about a six-month delay in the progression of the illness,” Dysken noted in a video interview provided by JAMA, adding, “This is comparable to the cholinesterase inhibitors. When one takes a look specifically at the effectiveness of the agents, it is about the same.”

“Since the cholinesterase inhibitors [galantamine, donepezil, rivastigmine], we have had very little to offer patients with mild-to-moderate dementia,” added co-author Mary Sano, PhD, professor of medicine at the Mount Sinai Health system and director of research at the James J. Peters Veteran’s Administration Medical Center in Bronx, NY.

“This trial showed that vitamin E delays progression of functional decline by 19% per year, which translates into 6.2 months benefit over placebo,” she said in a Mount Sinai press release.

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Therapy with alpha tocopherol, a fat-soluble vitamin E and antioxidant, has been studied in patients with moderately severe AD and in participants with mild cognitive impairment (MCI) but has not been studied in patients with mild to moderate AD, according to background in the study.

In this study, researchers examined the effectiveness and safety of vitamin E and a drug, memantine, which has been shown to be effective in patients with AD and moderately severe dementia and the combination for treatment of functional decline in patients with mild to moderate AD who were taking an acetyl cholinesterase inhibitor.

Participants were divided into four groups — 152 received 2,000 IU/day of vitamin E; 155 received 20 mg/d of memantine; 154 received a combination (n = 154), and 152 were given a placebo.

Functional decline was measured using the Alzheimer’s Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78).

Results indicated that, over the average follow-up time of 2.3 years, participants receiving vitamin E had slower functional decline than those receiving placebo, with the annual rate of decline in ADLs reduced by 19%. Study authors note that that reduction translates into a clinically meaningful delay in progression in the vitamin E group of 6.2 months. In addition, caregiver time was reduced by about two hours a day in that group.

Dysken said that, in comparison to placebo, “the amount of time the caregiver spent in taking care of the patient decreased over the period of time in the study. That difference was about two hours less time spent. The only comparison that met statistical significance was between vitamin E and memantine and again favoring vitamin E.”

In fact, no clinical benefit was detected for either memantine or the combination of vitamin E and memantine in the trial.

Differences in all-cause death and safety were only seen in 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).

“In contrast to the conclusion drawn from a 2005 meta-analysis of vitamin E, which showed that high-dose vitamin E (≥ 400 IU/d) may increase the risk of all-cause mortality, we found no significant increase in mortality with vitamin E,” the authors wrote. “The annual mortality rate was 7.3% in the alpha tocopherol group vs. 9.4% for the placebo group.”

“This was particularly important because a report in 2005 suggested that with vitamin E in doses over 400 international units a day, there was increased mortality that was proportional to the dose of vitamin E,” Dysken added. “This we did not find in our study and, as a matter of fact, in patients who took vitamin E, that mortality rate was the lowest compared to the other three groups.”

Noting that decline in functioning in AD is increasingly recognized as an important determinant of both patient quality of life and social and economic costs, the authors pointed out, “In the current study, the placebo group lost approximately three units more on the ADCS-ADL Inventory than the alpha tocopherol group. A loss of this magnitude could translate into either the complete loss of being able to dress or bathe independently, for example, or losing independence on any three different ADLs. Because vitamin E is inexpensive, it is likely these benefits are cost-effective as alpha tocopherol improves functional outcomes and decreases caregiver burden.”

Researchers were from a range of academic institutions as well as VAMCs in Minneapolis; New York; Cleveland; Washington; Miami; Baltimore; Dallas; Charleston, SC; Ann Arbor, MI; San Juan, PR; Bay Pines, FL, Boston; Seattle; Iowa City, IA; Salisbury, NC, and West Haven, CT

In terms of future research, Dysken suggested looking at other dosages of vitamin E.

“Higher doses have been used and have been found to be safe,” he pointed out. “Other antioxidants might also be tried to see if there is really any difference among different agents. Aerobic exercise, it is turning out, has benefits in patients with Alzheimer’s disease, so it might be very interesting to look at combination of vitamin E and aerobic exercise.”

1. Dysken MW, Sano M, Asthana S, Vertrees JE, et al.Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA. 2014 Jan 1;311(1):33-44. doi:10.1001/jama.2013.282834. PubMed PMID: 24381967.


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