- Click here for explanation of classification scheme.

To assess the efficacy of vitamin E in the treatment of Alzheimer's disease and prevention of progression of mild cognitive impairment to Alzheimer's disease. 

All unconfounded, double blind, randomized trials in which treatment with vitamin E at any dose was compared with placebo for patients with Alzheimer's disease or mild cognitive impairment were included.

Trials in which allocation to treatment was not randomized, or in which treatment allocation was not concealed were excluded.

Recruitment

• The Cochrane Dementia and Cognitive Improvement's Specialized Register was searched on January 8, 2007 using the following terms: vitamin E, vitamin-E, alpha-tocopherol
• The CDCIG Register contains records from major health care databases and ongoing trial databases and is updated regularly. 

Design

Systematic review 

Blinding used

Included trials were double-blind 

Intervention

Treatment with vitamin E at any dose compared with placebo

Statistical Analysis

• Two reviewers independently applied the selection criteria, assessed study quality, extracted and analyzed the data
• For each outcome measure data were sought on every patient randomized, and where such data were not available, an analysis of patients who completed treatment was conducted
• For continuous or ordinal variables, two possible approaches were taken to analyze the data
• For binary variables, the Peto method of the typical odds ratio was used
• The null hypothesis tested was that for any of the outcomes vitamin E has no effect compared with placebo.

Timing of Measurements 

Not applicable

Dependent Variables

• Global severity of dementia
• Time to development of possible Alzheimer's disease from mild cognitive impairment
• Global deterioration
• Cognitive function
• Behavioral disturbance
• Mood
• Activities of daily living
• Caregiver burden
• Quality of life
• Permanent physical disability
• Institutionalization
• Death.

Independent Variables

Vitamin E or placebo

Control Variables

 

• Initial N: Only two studies met inclusion criteria, original search results not reported
• Attrition (final N): Only two studies met inclusion criteria
  • One study of Alzheimer's disease, Sano, 1996, which had 341 subjects with probably Alzheimer's disease
  • One study of mild cognitive impairment, Petersen, 2005, which had 769 participants, 257 in the vitamin E group, 259 in the placebo group, and a third Donepezil group of 253 subjects not included in the review
• Age: Not reported
• Ethnicity: Not reported
• Other relevant demographics: Not reported
• Anthropometrics: Not reported
• Location: United States and Canada.

 

Key Findings

• The primary outcome used in the Alzheimer's disease study was survival time to the first of four endpoints:
  • Death
  • Institutionalization
  • Loss of two out of three basic activities of daily living
  • Severe dementia (defined as a global Clinical Dementia Rating of 3)
• The investigators reported the total numbers in each group who reached the primary endpoint within two years for participants completing the study; there appeared to be some benefit from vitamin E with fewer participants reaching endpoint: 58% (45 out of 77 completers) compared with 74% (58 out of 78 completers, a Peto odds ratio of 0.49 (95% confidence interval: 0.25 to 0.96).
• However, more participants taking vitamin E suffered a fall (12 out of 77 compared with four out of 78; odds ratio=3.07, 95% confidence interval: 1.09 to 8.62).
• It was not possible to interpret the reported results for specific endpoints or for secondary outcomes of cognition, dependence, behavioral disturbance and activities of daily living
• The primary outcome in the mild cognitive impairment study was the time to progression from mild cognitive impairment to possible or probable Alzheimer's disease
• A total of 214 of the 769 participants had progression to dementia, with 212 being classified as having possible or probable Alzheimer's disease
• There was no significant difference in the probability of progression from mild cognitive impairment to Alzheimer's disease between the vitamin E group and the placebo group
• There was no significant difference between the placebo group and the vitamin E group in adverse events
• Five subjects died in each group and 72 discontinued treatment in the vitamin E group and 66 in the placebo group. 

To date, only one randomized controlled trial has assessed the efficacy of vitamin E in the treatment of Alzheimer's disease patients and only one assessed the role of vitamin E in patients with mild cognitive impairment. In the vitamin E study for moderately severe Alzheimer's disease patients, a lower number of those taking vitamin E declined to incapacity over a two-year period compared with the placebo group, however, Alzheimer's disease patients taking vitamin E experienced a greater number of falls. In the mild cognitive impairment study, vitamin E (2,000 IU daily) produced no significant difference in the rate of progression to Alzheimer's disease compared to the placebo group.

There is no evidence of efficacy of vitamin E in the prevention or treatment of people with Alzheimer's disease or mild cognitive impairment. More research is needed to identify the role of vitamin E, if any, in the management of cognitive impairment.

Other:

Not reported

Only two studies met inclusion criteria.