Vitamin E

The study was conducted to determine if vitamin E (alpha-tocopherol) could improve cognitive function in patients with nasopharyngeal carcinoma and temporal lobe radionecrosis.

Participants were administered 1,000 IU of vitamin E twice daily for one year. Assessments were conducted prior to the initiation of vitamin E dispensal and after the completion of one year of treatment.

• The total number of study participants was 29.
• There were 19 participants in the treatment group and 10 in the control group.
• Participants had stable nasopharyngeal cancer without recurrence for more than five years. They had no mental, speech, or psychiatric problems.  
• The control group was matched for age, education, radiation dose, amount of time since radiation, and lesion volume.
• The mean age of the treatment group was 57.95 ± 9.32 years.
• The mean age of the control group was 57.1 ± 13.91 years. 
• The control group was 50% male and 50% female.
• The treatment group was 75% male and 25% female.

The study was a single-site project at the neurology clinic of Queen Elizabeth Hospital in Hong Kong.

The study employed a pre- and post-test design with a treatment and control group.

• Cantonese version of the Mini-Mental State Examination (MMSE) for global cognitive functioning
• Chinese version of the Category Fluency Test for expressive language ability
• Hong Kong List Learning Test (HKLLT) for verbal memory
• Visual Reproduction subtest of the Wechsler Memory Scale III (WMS-VR) for visual memory
• Computerized reaction time test, developed by author A. Chan, for sustained attention
• Computerized Cognitive Flexibility Test, developed by author A. Chan, for cognitive flexibility
• Questionnaire on cognitive function. The questionnaire had 8 subjective items assessing attention, reading, writing, memory, visual motor ability, expressive ability, planning, and computation skills. Scores ranged from 8 to 40, points with higher scores indicating better perceived performance.

There was no significant difference in cognitive performance at baseline between the two groups. In the treatment group, there was significant improvement from baseline on

• global cognition as measured by the MMSE (p = 0.035)
• verbal memory as measured by the HKLLT (p = 0.036) 
• visual memory as measured by the WMS-VR (p = 0.007), including immediate recall (p = 0.001) and 30-minute delayed recall (p = 0.000).

Improved executive function was also measured in the treatment group, as seen in average reaction times (p = 0.001) and scores on the Cognitive Flexibility Test (p = 0.04); these improvements were not found in the treatment group. No significant differences were found in sustained attention for either group. There was a slight, but not statistically significant, increase in participant ratings after one year of treatment for the treatment group. The control group reported a slight worsening of function on their subjective ratings (p = ns).

Vitamin E may be a promising complementary intervention for improvement in verbal and visual memory, global cognitive function, and cognitive flexibility.

• The study had a small sample size.
• There was no randomization, blinding, or placebo.
• Gender may have impacted some test results, as there are known gender differences in neuropsychological test performance. The treatment group had three times more men than women.

The study was conducted to test oral donepezil and oral vitamin E in patients with small-cell lung cancer after completion of all cancer therapy and prophylactic cranial irradiation.

A randomization procedure was conducted after participant stratification in the following ways.

• Baseline cognitive function on the Mini-Mental State Examination (MMSE) placed participants in three impairment groups: normal, mild to moderate, and severe.  
• Participants were categorized by age into two groups, 60 years or younger or older than 60 years.

The treatment group received 5 mg/day of oral donepezil, which increased to 10 mg/day after one month of therapy if tolerated well. Treatment group participants also received 1000 IU/day of oral vitamin E. The control group was given an identical oral placebo. Assessments were performed at study enrollment, one month, and every three months until cancer recurrence or treatment failure.

• The total number of participants enrolled over 15 months was 9.
• There were 4 participants in the treatment group and 5 participants in the control group.  
• All participants had a diagnosis of small-cell lung cancer.
• All participants had a limited disease status and similar prophylatic carnial irradiation.  
• All participants had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2.
• The mean age of the treatment group was 67, with a range of 65–69.
• The mean age of the control group mean was 67, with a range of 60–76.
• The treatment group was 100% male; the control group was 80% male and 20% female.

The study took place at the North Central Cancer Treatment Group and the Mayo Clinic.

The study was a double-blind, placebo-controlled trial.

• The Mini-Mental State Examination (MMSE) was used to measure global cognitive functioning. A three-point drop indicated treatment failure.
• A five-point drop on the Blessed Dementia Scale indicated treatment failure.
• The Common Terminology Criteria for Adverse Version 2.0 was also used. 

There were no notable differences in cognitive stability, adverse events, or quality of life between treatment arms. Only one patient, who received donepezil and vitamin E, manifested a three-point drop in cognitive scores as measured by the MMSE. There was a slight trend of increased gastrointestinal side effects among patients treated with donepezil and vitamin E.

The median time spent in the study was 42 or 69 days for the treatment or control group, respectively.

Due to low enrollment and retention, the effect of oral doses of vitamin E and donepezil on cognitive function could not be determined. 

• The study had a small sample size.
• Inclusion criteria seriously limited eligibility and enrollment.
• Participant withdrawal tended to occur sooner in the study for those receiving the medication intervention than among those in the control group. No explanation for subject withdrawals was provided.