1. Based on this double-blind randomized, controlled trial which evolved into a cohort study, asymptomatic men taking vitamin E, selenium or a combination of the two did not have decreased risk of dementia as compared to men taking placebo.
2. When the study transitioned from a randomized, controlled trial to a cohort study, there was a significant reduction in the size of the study population and supplement exposure decreased, which may have resulted in an under-powered study.
Evidence Rating Level: 2 (Good)
Study Rundown: Basic science research has suggested that oxidative stress plays a role in the development of dementia, however it is unclear if antioxidant supplements help to decrease the risk of dementia. This study, which was initially a double-blind RCT which then transitioned into a cohort study, aimed to determine if antioxidant supplements, vitamin E and selenium used alone or in combination, could decrease the risk of dementia in asymptomatic older men.
The incidence of dementia was 4.4%. However, men receiving vitamin E or selenium or both did not have a lower risk of dementia as compared to men taking placebo. All men were followed for 5.4 years but a subset of men were followed for an additional 6 years. Strengths of this study included an initial study population that was large and the randomized design, however at the time of change to a cohort design, there was a significant decrease in the size of the study population, exposure to the antioxidants, and there was reduced patient-years of follow up. All of this under-powered the study. Additionally, a positive result on the dementia screening tool did not always lead participants to follow up appropriately, which may have led to under-diagnosis of the disease. Lastly, the effects of earlier and longer administration of the studied antioxidants may be required to see appropriate effects.
Relevant Reading: Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment
In-Depth [prospective cohort]: This randomized trial was initially a part of a parent study SELECT (double-blind RCT to determine the effectiveness of antioxidant supplementation in preventing prostate cancer). The PREADViSE Trial (Prevention of Alzheimer’s Disease by Vitamin E and Selenium) included a subset from the SELECT trial of men 60 years and older without dementia between 2002 and 2008. These men also did not have any history of serious head injury or substance abuse. SELECT was supposed to continue until 2012, however in 2008 SELECT was stopped due to findings from a futility analysis. The PREADViSE trial continued as a cohort study where 56.6% of the original sample continued into the cohort. The original 7,540 men were randomized into four groups: vitamin E only, selenium only, both vitamin E and selenium or placebo. All participants were followed for 5.4 years to determine the development of dementia using a 2-stage screen. The men who continued in the PREADViSE cohort were followed for an additional 6 years. Cox proportional hazards models and modified intention-to-treat was used for statistical analysis.
Dementia incidence was 4.4% (325 of 7338 men) and risk of dementia was not significantly different between the four study arms: vitamin E hazard ratio (HR) 0.88 (95% CI 0.64-1.20), selenium HR 0.83 (95% 0.60-1.13) and combination of vitamin E and selenium HR 1.00 (95% CI 0.75-1.35) as compared to placebo. These hazard ratios were adjusted for participant demographic information and baseline self-reported comorbidities.
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