James A Mastrianni MD, PhD

The treatments for Alzheimer’s disease are quite limited, so the search for adjunctive therapies that delay disease progression or symptoms thereof are highly desired. A daily dose of 2000 IU of vitamin E was previously shown by Sano et al to delay progression of moderate Alzheimer’s disease by ~7 months, but evidence in patients with earlier-stage Alzheimer’s disease was lacking. In addition, 2 years after that landmark study by Sano et al, the routine use of vitamin E in Alzheimer’s disease fell sharply out of favor as a result of a meta-analysis study that concluded that vitamin E doses higher than 400 IU/day were associated with an increased risk of all-cause mortality.¹

A current study by Dysken et al found that a twice-daily dose of 1000 IU of vitamin E resulted in a significant reduction in the rate of functional loss in patients with mild to moderate Alzheimer’s disease, as measured by the Alzheimer Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory.² In addition, the caregiver burden, as measured by the Caregiver Activity Survey (CAS), was reduced in the vitamin E treatment group, but only compared with the memantine group and not the placebo group.

Interestingly, the investigators re-confirmed the lack of efficacy of 20 mg/day memantine in mild Alzheimer’s disease, but also found that this dose negated the beneficial effect of vitamin E, when the two were used in combination. Although vitamin E had no effect on memory as measured by the Mini Mental State questionnaire and Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-cog), the delay in functional decline translated into a 6.2-month delay in disease progression compared with placebo-treated patients.

The Dysken study is important for multiple reasons. First, its findings are consistent with the findings of Sano et al, raising confidence in the data. Second, the benefit of vitamin E is now extended to earlier stages of Alzheimer’s disease. Third, which is also a critical finding regarding the clinical application of these favorable results, the investigators found no elevation in mortality rate in the cohorts receiving vitamin E. Thus, this important study establishes vitamin E as a safe and effective agent that should be routinely considered when treating patients with mild to moderate Alzheimer’s disease.