AGS 2009: High-Dose Vitamin E Slows Functional Decline in Alzheimer's Disease

Kathleen Louden

May 05, 2009

May 5, 2009 (Chicago, Illinois) — Patients with Alzheimer's disease who receive high-dose vitamin E combined with a cholinesterase inhibitor have less long-term deterioration in their ability to perform activities of daily living than those who do not receive vitamin E, a new study found. The results were presented here at the American Geriatrics Society (AGS) Annual Scientific Meeting.

Treatment benefit increased with time over 5 years, the authors report. This result may explain why some previous studies of vitamin E in patients with Alzheimer's disease showed no effect at only 1 year, lead author Michael Flaherty said in an interview with Medscape Internal Medicine. Mr. Flaherty performed the research during a research fellowship at Massachusetts General Hospital in Boston and is now a second-year medical student at the University of New England College of Osteopathic Medicine in Biddeford, Massachusetts.

"Many neurologists continue to prescribe vitamin E for their Alzheimer's patients, but whether it slows progression of dementia is unclear," Mr. Flaherty said. "We found out there is promise for vitamin E in this disease."

The clinical-effectiveness study enrolled 540 patients with probable Alzheimer's disease (324 women) who had a mean age of nearly 74 years. All were receiving 1 of the following cholinesterase inhibitors: donepezil, rivastigmine, or galantamine (800 to 1000 U twice daily). In addition, 208 patients received vitamin E (800 to 2000 IU/day); 49 received anti-inflammatory medications, mainly nonsteroidal anti-inflammatory drugs, but no vitamin E; 177 patients received both vitamin E and anti-inflammatory drugs; and 106 received neither.

Long-Term Benefits

Every 6 months, the patients had a cognitive assessment using the Blessed Dementia Scale's Information-Memory-Concentration subscale and an evaluation of their function with the Weintraub Activities of Daily Living (ADL) Scale. The mean follow-up was 3.1 years. The authors annually calculated Cohen's d effect sizes for 5 years based on mixed-effects regression analyses.

Vitamin E treatment showed small to medium effect sizes in slowing functional decline, the abstract reports. For vitamin E, the ADL Cohen's d significantly increased, from 0.20 in year 1 (P = .02) to 0.42 by year 5 (P < .001).

Anti-inflammatory drugs showed a small effect size in slowing cognitive decline, with the Cohen's d for the dementia scale going from 0.12 in year 1 to 0.22 by year 5 (P = .006).

The study did not assess safety. Mr. Flaherty said further studies are needed to determine the risks and benefits of high-dose vitamin E and anti-inflammatory treatment, as well as the appropriate doses.

Safety a Concern

However, because some studies have shown an increased risk for death with vitamin E doses greater than 400 IU/day, high-dose vitamin E therapy for Alzheimer's disease fell out of favor a few years ago, according to an expert on Alzheimer's disease. That expert, Sharon Brangman, MD, director of the Central New York Alzheimer's Disease Center and chief of the Division of Geriatric Medicine at SUNY Upstate Medical University in Syracuse, told Medscape Internal Medicine in a phone interview, "We don't know if the benefit is worth the risks of high-dose vitamin E. We suggest taking no more than 400 IU per day."

Dr. Brangman, who is president-elect of AGS and who was not involved with the study, said: "I don't think this study alone gives enough information to drive clinical therapy. We need more research."

However, she added that most research on therapies for Alzheimer's disease is focusing on new agents, such as "amyloid busters."

This study was funded by the National Institutes of Health, Massachusetts Alzheimer's Disease Research Center, and the American Federation for Aging Research. Mr. Flaherty has disclosed no relevant financial relationships, but 1 of his coauthors, Alireza Atri, MD, PhD, from Massachusetts General Hospital in Boston, reported receiving payment for lectures or consulting from Eisai, Forest, Merck, Novartis, and Pfizer. Dr. Brangman has disclosed no relevant financial relationships.

American Geriatrics Society (AGS) 2009: Abstract A117. Presented April 30, 2009.

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