This study contains both potentially good and bad news for Alzheimer’s disease therapy, Dr. Denis Evans and his coauthors wrote in an accompanying editorial (JAMA 2014;311:29-30).
"For memantine therapy in this context, the trial results are not encouraging," wrote Dr. Evans. "Use in individuals with milder AD may be widespread, despite little evidence suggesting the agent is beneficial at this level of disease severity. This trial ... does not provide any new data to support its use."
For vitamin E, however, the results are more intriguing, especially in light of findings from prior studies.
"A previous trial among individuals with moderate to severe AD found delayed disease progression with 2,000 IU/day of [vitamin E] both alone and in combination with selegiline (N. Engl. J. Med. 1997;336:1216-22). The results of a trial of vitamin E therapy among people with mild cognitive impairment were null, however, as were the results of trials examining the effects of vitamin E on cognitive function among people with normal cognition."
The study begs three questions, Dr. Evans noted. First, is the use of functional ability a more sensitive measure of AD progression than cognition, which showed no improvement?
Second, why did the secondary measures of caregiver time and dependence not confirm the primary finding of a slower functional decline?
Third, how would vitamin E work to delay decline in Alzheimer’s? "Much attention is focused on its antioxidant properties, but this mechanism is not specific for AD," Dr. Evans wrote.
"Although these considerations do not lessen the significance of the difference found between the group randomized to vitamin E and the group randomized to placebo for the primary outcome, this difference would have been more convincing if also supported by parallel improvements in the relevant secondary outcomes and by a vitamin E mechanism of action more specific to AD."
Dr. Evans is the Alla V. and Solomon Jesmer Professor of Medicine at Rush Medical Center, Chicago. He had no commercial financial disclosures. A coauthor, Dr. Martha Clare Morris, reported receiving consultant fees from Nutrispective.
