Literature Review

Vitamin E May Slow Functional Decline in Alzheimer’s Disease



High-dose vitamin E significantly slowed functional decline over two years in patients with mild to moderate Alzheimer’s disease, researchers reported in the January 1 issue of JAMA.

Compared with placebo, 2,000 IU daily of vitamin E reduced disease progression by 19% per year, according to Maurice W. Dysken, MD, and his colleagues.

Patients who took vitamin E scored about three units higher on a measure of daily function, wrote Dr. Dysken, of the Minneapolis Veterans Affairs Health Care System. “A loss of this magnitude could translate into either the complete loss of being able to dress or bathe independently, or losing independence on any three activities of daily living.”

Vitamin E also proved better than memantine at delaying progression, although the difference was not statistically significant. Paradoxically, the combination of vitamin E and memantine was significantly less helpful than either intervention alone.

The four-year study randomized 613 patients with mild to moderate Alzheimer’s disease into four treatment groups: 2,000 IU/day of vitamin E, 20 mg/day memantine, a combination of both, or placebo.

The primary outcome was change on the Alzheimer’s Disease Cooperative Study/Activities of Daily Living Inventory (ADCS–ADL).

The patients had a mean age of 79; 97% were men. About half had at least one apolipoprotein e4 allele. The mean baseline score on the ADCS–ADL was 57 on a scale of 0 to 78, with lower numbers representing worse function.

The final analysis contained data on 561 patents. The dropout rate was similar among the groups; most of the dropout rate was due to death during the study. Only three participants withdrew from medication-related adverse events.

The mean follow-up time was slightly more than two years. For patients receiving vitamin E, the mean decline on the ADCS–ADL from baseline was 3.15 units less than the decline in the placebo group. “The treatment effect translates into a clinically meaningful delay in progression in the [vitamin E group] of 6.2 months,” the investigators wrote. “A delay in progression was sustained throughout most of the trial, with delays at 1, 2, 3, and 4 years of 10.6, 8.7, 9.3, and 1.8 months, respectively.”

The placebo group also declined more than both the memantine and combination groups, but those differences were not statistically significant. However, there was a significant negative treatment interaction between vitamin E and memantine, with patients who took the combination performing worse than patients taking either intervention alone.

No between-group differences were observed in the rate of cognitive decline or neuropsychiatric symptoms. Patients in the vitamin E group did require about two hours less of caregiver time per day, compared with those on memantine, but that difference was not statistically significant, with a confidence interval of 0.63 to 3.71.

Despite being statistically nonsignificant, the reduction in caregiver time was clinically meaningful and could have “a major effect on informal and direct medical costs,” said the authors. “The loss of the ability to perform ADLs is associated not only with increased caregiver burden, but also with nursing home placement.”

Any “infection or infestation” was the only category of adverse events reported significantly more commonly in both the memantine and combination groups. The most common, occurring in at least 5% more of treated than placebo patients, were falls, bleeding, pneumonia, and urinary tract infections.

Annual mortality was similar among the groups: 7% for the vitamin E group, 11% for the memantine group, and 9% for both the combination and placebo groups.

Michele G. Sullivan

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