Vitamin E doesn't slow progression to Alzheimer's disease
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* David Spurgeon

Vitamin E, a widely used early intervention for Alzheimer's disease, had no effect on 769 patients with mild cognitive impairment enrolled in a three year randomised placebo controlled doubleblind study published online on 13 April by the *New England Journal of Medicine* (www.nejm.org, doi:10.1056/NEJMoa050151). The study also showed that although donepezil (Aricept)showed no slowing of the rate of progression of the disease after three years compared with placebo, the drug was associated with a lower rate of progression during the first 12 months of treatment. Patients with an apolipoprotein E allele, which is a risk factor for Alzheimer's disease, showed a significant effect at one, two, and three years.

Results of the study, from the Alzheimer's Disease Cooperative Study Group, and an accompanying editorial by Deborah Blacker of Massachusetts General Hospital and Harvard University ([dx.doi.org/10.1056/NEJMe058086](http://dx.doi.org/10.1056/NEJMe058086)) were given early release to coincide with presentation at the American Academyof Neurology meeting in Miami, Florida. They will appear in the journal on 9 June.

Dr Blacker said that the implications of the study for primary care medicine and for public health were enormous. She also said that the trial represents “a major step forward in the literature on trials of treatment for mild cognitive impairment.” The biggest news is the disappointing lack of efficacy of vitamin E, but the news about donepezil “does leave us with some hope.”

The findings come just a few weeks after the National Institute for Clinical Excellence published draft guidance on the treatment of Alzheimer's disease, saying that donepezil should no longer be prescribed on the NHS for new patients. The guidance said, however, that patients already receiving the drug could continue to do so. The guidance produced a storm of protest (*BMJ* 2005;330:495, 5 Mar).

Alzheimer's disease developed in 212 of the 769 patients enrolled in the study. The overall rate of progression from mild cognitive impairment to early Alzheimer's disease was 16% a year. Probability of progression to Alzheimer's disease did not differ significantly from the placebo group in the vitamin E group (hazard ratio 1.02, 95% confidence interval 0.74 to 1.41) or in the donepezil group (0.80, 0.57 to 1.13) in the three years of treatment.

Analyses of the treatment effects at six month intervals showed that compared with the treatment group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first year of the study (P=0.04), a finding supported by secondary outcome measures. Amongcarriers of one or more apolipoprotein E e4 alleles, the benefit of donepezil was evident throughout the three year follow-up. But there were insufficient data to warrant recommending apolipoprotein E genotyping in people with mild cognitive impairment.

Dr Blacker said that lessons from the study are firstly that symptoms of memory loss in older people should be taken seriously because they may be the beginnings of Alzheimer's disease. Secondly, donepezil may offer some benefit, but it will be quite limited and transient. And, thirdly and most importantly, early intervention with vitamin E does not delay the onset of Alzheimer's disease. Despite this, Dr Blacker expects that current studies of a wide range of agents aimed at halting or delaying the advance of pathologic brain lesions could show some effect.