What is the role of antioxidants in the treatment of Alzheimer disease (AD) in Down syndrome (DS)?

Updated: Nov 13, 2019
  • Author: Norberto Alvarez, MD; Chief Editor: Jasvinder Chawla, MD, MBA  more...
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Answer

Data suggest that free radicals may contribute to neurodegeneration in AD, but clinical trials have not consistently shown antioxidants to be efficacious. Several studies have addressed this issue, few of them in persons with DS.

A study of the use of lipoic acid in persons with DS failed to show any clinical impact. [129] A Cochrane report also found no evidence of benefit and suggested that lipoic acid should not be recommended for the treatment of dementia. [130]

Administration of acetyl-L-carnitine to improve visual memory and attention was reported in the only study done in persons with DS. This effect was not seen in a control group of persons with mental deficiency but no DS, suggesting some specificity. [131] Other studies in persons with mild cognitive impairment and AD also showed some improvement. Acetyl-L-carnitine was given to 40 individuals with DS in a double-blind protocol for 6 months, but it yielded no benefit in persons with DS. [132] At present, routine use of this medication is not recommended.

A 2-year randomized, double-blind, placebo-controlled trial assessed daily oral antioxidant supplementation (900 IU of alpha-tocopherol, 200 mg of ascorbic acid, and 600 mg of alpha-lipoic acid) in 53 persons with DS and dementia. [133] Although supplementation was safe, it yielded no improvement with respect to cognitive function or stabilization of cognitive decline.

Increased antioxidant effects in cells in patients with AD may improve some symptoms; however, a Cochrane meta-analysis found no evidence to support the use of melatonin in persons with dementia. [134]

Some studies suggested that diets containing high amounts of vitamin E could prevent dementia [135] ; however, other studies disagree. [136] A Cochrane review also found no solid evidence for the use of vitamin E in AD but identified enough benefit to justify further studies. [137]

Vitamins B-6, B-12, and folic acid are cofactors in the metabolism of homocysteine that might accumulate if there is a deficiency of these vitamins. A high level of homocysteine is a risk factor for the development of AD. Administration of 5 mg/day of folic acid, either alone or in combination with 5 mg/day of vitamin B-6 or 100 μg of B-12 (or both; see folic acid/cyanocobalamin/pyridoxine), decreased the blood levels of homocysteine in persons with DS. [138] No other studies have evaluated the use of these vitamins in persons with DS. In general, the evidence available does not demonstrate a beneficial effectofthesevitaminsin the prevention or treatment of AD.

The herbal product ginkgo biloba is probably the most commonly used alternative treatment for the prevention of age-related cognitive decline. [139] The information available is still controversial, with studies showing some mild benefit and others failing to show any positive change. [140] The only study of gingko involving 2 teenagers with DS showed some benefits in social and academic skills. [141]

Curcumin is an herb that is used to preserve food; it is widely consumed in India and might be related to the lower incidence of AD in India. Curcumin is a potent antioxidant and anti-inflammatory. There is no investigation of the effect of curcumin in persons with DS.

A 2015 meta-analysis failed to show a benefit with antioxidants. [124]


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