Alpha tocopherol, a fat-soluble vitamin (E) and antioxidant, has been studied in patients with moderately severe Alzheimer disease (AD) and in participants with mild cognitive impairment (MCI) but has not been studied in patients with mild to moderate AD. In patients with moderately severe AD, vitamin E was shown to be effective in slowing clinical progression. The drug memantine has been shown to be effective in patients with AD and moderately severe dementia, according to background information in the article.
Maurice W. Dysken, M.D., of the Minneapolis VA Health Care System, and colleagues examined the effectiveness and safety of vitamin E, memantine, and the combination for treatment of functional decline in patients with mild to moderate AD who were taking an acetylcholinesterase inhibitor (a chemical that increases the level and duration of action of the neurotransmitter acetylcholine). The trial included 613 patients at 14 Veterans Affairs medical centers. Participants received either 2,000 IU/day of vitamin E (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). Change in functional decline was gauged via the Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78).
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 percent. This treatment effect translates into a clinically meaningful delay in progression in the vitamin E group of 6.2 months. Neither memantine nor the combination of vitamin E and memantine showed clinical benefit in this trial.
In addition, caregiver time was reduced by about 2 hours per day in the vitamin E group.
All-cause death 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).
The authors write that the current study is one of the largest and longest treatment trials in patients with mild to moderate AD, and that it provides information on reported safety issues of vitamin E, with results from previous trials resulting in decreased prescribing for patients with AD. "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 annual mortality rate was 7.3 percent in the alpha tocopherol group vs. 9.4 percent for the placebo group."
The researchers note that decline in functioning in AD is increasingly recognized as an important determinant of both patient quality of life and social and economic costs. "In the current study, the placebo group lost approximately 3 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 bath independently, for example, or losing independence on any 3 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."
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Vitamin E, Memantine, and Alzheimer Disease
Denis A. Evans, M.D., of Rush University Medical Center, Chicago, and colleagues comment on the findings of this study in an accompanying editorial.
"Many features of the trial by Dysken et al reflect the best in trials of AD therapy, especially its size, duration, and separation from commercial motivation. However, as with almost all previous AD trials, the therapeutic effect seen was modest and more relevant to AD symptoms and consequences than to reversal of the disease process. The importance of treating patients with AD is clear, but finding the best balance between treatment and prevention efforts is challenging for this grim disease affecting millions of people from all developed countries."
"Considering the difficulties inherent in trying to treat rather than prevent very high-prevalence diseases and the limitations thus far of the therapeutic efforts for people with AD, shifting to more emphasis on prevention seems warranted."
Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc.
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