Down syndrome and dementia: A randomized, controlled trial of antioxidant supplementation

Randomized, placebo-controlled trial in adults with Down syndrome and Alzheimer-type dementia receiving standard dementia care at two ambulatory clinic sites in California. The antioxidant arm had 29 participants randomized, with 23 evaluated at year 1 and 16 evaluated at year 2.

Oral antioxidant combination: 900 IU alpha-tocopherol, 200 mg ascorbic acid, and 600 mg alpha-lipoic acid daily for 2 years, taken as one capsule at breakfast and two capsules with the evening meal. A standard multivitamin tablet was also given once daily; the regimen was compared with placebo.

Antioxidant supplementation was safe and well tolerated, but it did not improve or stabilize cognitive function compared with placebo over 2 years. The primary cognitive outcome, DMR SOC, was null (slope 0.34 points per 1/2-year; 95% CI -1.39 to 2.07; P = 0.70), with no benefit at 1 year (difference 1.69; 95% CI -2.92 to 6.31; P = 0.47) or 2 years (difference 3.71; 95% CI -4.81 to 12.22; P = 0.39). SIB was also null at 1 year (difference -9.08; 95% CI -23.86 to 5.70; P = 0.23) and 2 years (difference -1.51; 95% CI -13.65 to 10.63; P = 0.81). Most secondary measures were similarly not significant, with isolated mixed signals on some Vineland Adaptive Behavior Scales domains. Overall, the findings support feasibility of dementia trials in Down syndrome but do not show clinical efficacy for this antioxidant regimen.

Small active-arm sample and substantial attrition over time limited power, with only 23 participants evaluated at year 1 and 16 at year 2. The trial was conducted at two California clinic sites, which may limit generalizability. Interpretation is also constrained by reliance on a specific cognitive/functional test battery and the absence of a demonstrated benefit on the primary endpoint.