Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer’s Disease by Vitamin E and Selenium Trial (PREADViSE)

Abstract

IMPORTANCEOxidative stress is an established dementia pathway, but it is unknown if the use of antioxidant supplements can prevent dementia.OBJECTIVE To determine if antioxidant supplements (vitamin E or selenium) used alone or in combination can prevent dementia in asymptomatic older men. DESIGN, SETTING, AND PARTICIPANTSThe Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADViSE) trial began as a double-blind randomized clinical trial in May 2002, which transformed into a cohort study from September 2009 to May 2015. The PREADViSE trial was ancillary to the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized clinical trial of the same antioxidant supplements for preventing prostate cancer, which closed in 2009 owing to findings from a futility analysis. The PREADViSE trial recruited 7540 men, of whom 3786 continued into the cohort study. Participants were at least 60 years old at study entry and were enrolled at 130 SELECT sites, and Cox proportional hazards models were used in a modified intent-to-treat analysis to compare hazard rates among the study arms. INTERVENTIONSParticipants were randomized to vitamin E, selenium, vitamin E and selenium, or placebo. While taking study supplements, enrolled men visited their SELECT site and were evaluated for dementia using a 2-stage screen. During the cohort study, men were contacted by telephone and assessed using an enhanced 2-stage cognitive screen. In both phases, men were encouraged to visit their physician if the screen results indicated possible cognitive impairment.MAIN OUTCOMES AND MEASURES Dementia case ascertainment relied on a consensus review of the cognitive screens and medical records for men with suspected dementia who visited their physician for an evaluation or by review of all available information, including a functional assessment screen. RESULTSThe mean (SD) baseline age of the 7540 participants was 67.5 (5.3) years, with 3936 (52.2%) reporting a college education or better, 754 (10.0%) reporting black race, and 505 (6.7%) reporting Hispanic ethnicity. Dementia incidence (325 of 7338 men [4.4%]) was not different among the 4 study arms. A Cox model, which adjusted incidence for participant demographic information and baseline self-reported comorbidities, yielded hazard ratios of 0.88 (95% CI, 0.64-1.20) for vitamin E, 0.83 (0.60-1.13) for selenium, and 1.00 (0.75-1.35) for the combination compared with placebo.CONCLUSIONS AND RELEVANCE Neither supplement prevented dementia. To our knowledge, this is the first study to investigate the long-term association of antioxidant supplement use and dementia incidence among asymptomatic men.

Aiding the discovery of new treatments for dementia by uncovering unknown benefits of existing medications

“…Pharmacoepidemiology and observational research has played a role historically in the identification of potential therapeutic targets for disease-modifying treatments to treat dementia. In t' Veld et al conducted a large populationbased cohort study and examined an association between nonsteroidal anti-inflammatory drug use and the reduced risk of dementia and AD [10], and others have used similar study designs to detect potential protective effects and/or risks of antihypertensive medications [11,12], antioxidants [13], and hormone therapies [14]. These large prospective observational studies are useful for studying specific treatments of interest, but they are expensive and cannot be easily scaled to study many exposures.…”

Can Antioxidant Supplement Prevent Dementia?

“…Additionally, a Cox model shows that hazard ratios for incident dementia is 0.88 (95% CI, 0.64-1.20) for vitamin E, 0.83 (95% CI, 0.60-1.13) for selenium, and 1.00 (95% CI, 0.75-1.35) for vitamin E combined with selenium compared with placebo. This study indicates that vitamin E and selenium cannot prevent dementia [2].…”

“…In addition, this study indicates that the use of vitamin E or vitamin C supplements alone, with multivitamins alone, or with vitamin B-complex supplements cannot lower the risk of Alzheimer disease [1,2].…”

The effect of physical activity, pharmacologic interventions, over-the-counter supplements and cognitive training in preventing Alzheimer’s disease, mild cognitive impairment and related dementias: an overview

“…Trys ty ri mai (n = 12 830), ku riø truk më -nuo 9 iki 10 me tø, ty rë ga li mà vi ta mi no E áta kà ADRD ser ga mu mui, kas dien var to jant nuo 270 iki 400 mg. Ty ri muo se da ly va vo nor ma liø kog ni ty vi niø ge bë ji mø vy rai [64] ir mo te rys [65,66]. Ty ri me, ku ria me da ly va vo vy rai, nu sta ty ta, kad, ly ginant su pla ce bo gru pe, vi ta mi no E var to ji mas ne da rë jokios áta kos ti ki my bei su sirg ti de men ci ja.…”