Vitamin E in Aging Persons with Down Syndrome: A Randomized, Placebo-controlled Clinical Trial

Overview

Journal Neurology

Specialty Neurology

Date 2016 May 11

PMID 27164691

Citations 24

Authors

Mary Sano

Paul S Aisen

Howard F Andrews

Wei-Yann Tsai

Florence Lai

Arthur J Dalton

Affiliations

Soon will be listed here.

Abstract

Objective: To determine whether vitamin E would slow the progression of cognitive deterioration and dementia in aging persons with Down syndrome (DS).

Methods: A randomized, double-blind controlled clinical trial was conducted at 21 clinical sites, and researchers trained in research procedures recruited adults with DS older than 50 years to participate. Participants were randomly assigned to receive 1,000 IU of vitamin E orally twice daily for 3 years or identical placebo. The primary outcome was change on the Brief Praxis Test (BPT). Secondary outcomes included incident dementia and measures of clinical global change, cognition, function, and behavior.

Results: A total of 337 individuals were randomized, 168 to vitamin E and 169 to placebo. Both groups demonstrated deterioration on the BPT with no difference between drug and placebo. At baseline, 26% were diagnosed with dementia and there was an overall rate of incident dementia of 11%/year with no difference between groups. There was no effect on the secondary outcome measures. Though numerically higher in the treatment group, there was no difference in the number of adverse events (p = 0.079) and deaths (p = 0.086) between groups.

Conclusions: Vitamin E did not slow the progression of cognitive deterioration in older individuals with DS.

Classification Of Evidence: This study provides Class II evidence that vitamin E does not significantly slow the progression of cognitive deterioration in aging persons with DS.

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References

Brugge K, Nichols S, Saitoh T, Trauner D . Correlations of glutathione peroxidase activity with memory impairment in adults with Down syndrome. Biol Psychiatry. 2000; 46(12):1682-9. DOI: 10.1016/s0006-3223(99)00026-8. View

Bruce A, Malfroy B, Baudry M . beta-Amyloid toxicity in organotypic hippocampal cultures: protection by EUK-8, a synthetic catalytic free radical scavenger. Proc Natl Acad Sci U S A. 1996; 93(6):2312-6. PMC: 39792. DOI: 10.1073/pnas.93.6.2312. View

Mann D, YATES P, Marcyniuk B . Alzheimer's presenile dementia, senile dementia of Alzheimer type and Down's syndrome in middle age form an age related continuum of pathological changes. Neuropathol Appl Neurobiol. 1984; 10(3):185-207. DOI: 10.1111/j.1365-2990.1984.tb00351.x. View

Busciglio J, Pelsman A, Wong C, Pigino G, Yuan M, Mori H . Altered metabolism of the amyloid beta precursor protein is associated with mitochondrial dysfunction in Down's syndrome. Neuron. 2002; 33(5):677-88. DOI: 10.1016/s0896-6273(02)00604-9. View

Sano M, Ernesto C, Thomas R, Klauber M, Schafer K, Grundman M . A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med. 1997; 336(17):1216-22. DOI: 10.1056/NEJM199704243361704. View

Dysken M, Sano M, Asthana S, Vertrees J, Pallaki M, Llorente M . Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA. 2014; 311(1):33-44. PMC: 4109898. DOI: 10.1001/jama.2013.282834. View

Lott I, Doran E, Nguyen V, Tournay A, Movsesyan N, Gillen D . Down syndrome and dementia: seizures and cognitive decline. J Alzheimers Dis. 2012; 29(1):177-85. PMC: 3406603. DOI: 10.3233/JAD-2012-111613. View

Janicki M, Dalton A . Prevalence of dementia and impact on intellectual disability services. Ment Retard. 2000; 38(3):276-88. DOI: 10.1352/0047-6765(2000)038<0276:PODAIO>2.0.CO;2. View

Schupf N, Kapell D, Lee J, Zigman W, Canto B, Tycko B . Onset of dementia is associated with apolipoprotein E epsilon4 in Down's syndrome. Ann Neurol. 1996; 40(5):799-801. DOI: 10.1002/ana.410400518. View

10.

Smith M, Perry G, Richey P, Sayre L, Anderson V, Beal M . Oxidative damage in Alzheimer's. Nature. 1996; 382(6587):120-1. DOI: 10.1038/382120b0. View

11.

Markesbery W, Lovell M . Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease. Neurobiol Aging. 1998; 19(1):33-6. DOI: 10.1016/s0197-4580(98)00009-8. View

12.

Pratico D, Iuliano L, Amerio G, Tang L, Rokach J, Sabatino G . Down's syndrome is associated with increased 8,12-iso-iPF2alpha-VI levels: evidence for enhanced lipid peroxidation in vivo. Ann Neurol. 2000; 48(5):795-8. View

13.

Kishnani P, Sommer B, Handen B, Seltzer B, Capone G, Spiridigliozzi G . The efficacy, safety, and tolerability of donepezil for the treatment of young adults with Down syndrome. Am J Med Genet A. 2009; 149A(8):1641-54. DOI: 10.1002/ajmg.a.32953. View

14.

Wisniewski K, Wisniewski H, Wen G . Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann Neurol. 1985; 17(3):278-82. DOI: 10.1002/ana.410170310. View

15.

Tyrrell J, Cosgrave M, McCarron M, McPherson J, Calvert J, Kelly A . Dementia in people with Down's syndrome. Int J Geriatr Psychiatry. 2001; 16(12):1168-74. DOI: 10.1002/gps.502. View

16.

Lai F, Williams R . A prospective study of Alzheimer disease in Down syndrome. Arch Neurol. 1989; 46(8):849-53. DOI: 10.1001/archneur.1989.00520440031017. View

17.

Galasko D, Peskind E, Clark C, Quinn J, Ringman J, Jicha G . Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol. 2012; 69(7):836-41. PMC: 3661272. DOI: 10.1001/archneurol.2012.85. View

18.

Miller 3rd E, Pastor-Barriuso R, Dalal D, Riemersma R, Appel L, Guallar E . Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2004; 142(1):37-46. DOI: 10.7326/0003-4819-142-1-200501040-00110. View

19.

Zigman W, Schupf N, SERSEN E, Silverman W . Prevalence of dementia in adults with and without Down syndrome. Am J Ment Retard. 1996; 100(4):403-12. View

20.

Petersen R, Thomas R, Grundman M, Bennett D, Doody R, Ferris S . Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005; 352(23):2379-88. DOI: 10.1056/NEJMoa050151. View