Other Agents

Vitamin E (alpha-tocopherol)

This agent is not currently US-FDA approved for the prevention or treatment of AD.

Proposed Mechanism of Action in AD
Prevents neuronal cell damage by inactivating toxic free radicals (antioxidant) in the CNS.

What is the Evidence?
A recently published observational study¹⁸ determined that in a large cohort of Japanese-American men, a significant protective effect was found for vascular dementia in men who had reported taking both vitamin E and C supplements (odds ratio [OR], 0.12). They also appeared to be protected against mixed or other types of dementia (OR, 0.31). No protective effect was found for Alzheimer's dementia (OR, 1.81).

From the most often cited study by Sano and colleagues¹⁹, it was concluded that in patients with moderately severe impairment from Alzheimer's disease, treatment with selegiline or high dose Vitamin E slowed the progression to primary endpoints - death, institutionalization, loss of the ability to perform basic activities of daily living, or severe dementia. A total of 341 patients received the selegiline 10 mg/day, Vitamin E, 2000 IU/day, both selegiline and Vitamin E, or placebo for two years under double blind conditions. There was delayed progression to outcome in the treatment groups (placebo 440 days, selegiline 655 days, Vitamin E 670 days, combined treatment 585 days). A common criticism of this study is covariate analysis had to be used before a treatment effect could be demonstrated because the placebo and active treatment groups had significantly different baseline MMSE scores. Because of Vitamin E's numerical, but not statistically significant advantage over selegiline in this study, favorable adverse effect profile, and considerably lesser cost, it is considered to be the preferred treatment.

Most Common Adverse Effects
High doses of Vitamin E have been associated with increased clotting time, easy bleeding and bruising. Due to the increased risk of bleeding, concomitant use with warfarin or NSAIDs may be problematic.