High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: A randomized controlled trial

JAMA

Volumn 300, Issue 15, 2008, Pages 1774-1783

  Aisen, Paul S ^a   Schneider, Lon S ^c   Sano, Mary ^d   Diaz Arrastia, Ramon ^e   Van Dyck, Christopher H ^f   Weiner, Myron F ^e   Bottiglieri, Teodoro ^g   Jin, Shelia ^b   Stokes, Karen T ^a   Thomas, Ronald G ^a,b   Thal, Leon J ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^d MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^f YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g BAYLOR UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYANOCOBALAMIN; FOLIC ACID; HOMOCYSTEINE; PLACEBO; PYRIDOXINE; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); VITAMIN B COMPLEX;

AGED; ALZHEIMER DISEASE; AMINO ACID BLOOD LEVEL; ARTHRALGIA; ARTICLE; BLURRED VISION; CLINICAL FEATURE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DEPRESSION; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DYSPNEA; FEMALE; FOLLOW UP; HEADACHE; HUMAN; HYPERHIDROSIS; JOINT SWELLING; MAJOR CLINICAL STUDY; MALE; MENTAL DETERIORATION; MULTICENTER STUDY; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RATING SCALE; RESTLESSNESS; TREATMENT OUTCOME; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; VITAMIN SUPPLEMENTATION; BLOOD; COGNITION; COGNITIVE DEFECT; DIET SUPPLEMENTATION; GENETICS; PATHOPHYSIOLOGY; PSYCHOLOGICAL RATING SCALE;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; COGNITION; COGNITION DISORDERS; DIETARY SUPPLEMENTS; FEMALE; FOLIC ACID; HOMOCYSTEINE; HUMANS; MALE; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); PSYCHIATRIC STATUS RATING SCALES; VITAMIN B 12; VITAMIN B 6; VITAMIN B COMPLEX;

EID: 54049106963     PISSN: 00987484     EISSN: 15383598     Source Type: Journal    
DOI: 10.1001/jama.300.15.1774     Document Type: Article

References (40)

1. Aisen PS. The development of anti-amyloid therapy for Alzheimer's disease: from secretase modulators to polymerisation inhibitors. CNS Drugs. 2005;19(12):989-996.
2. Fillit HM, Refolo LM. Tau and Alzheimer's disease: the long road to anti-tangle therapeutics. J Mol Neurosci. 2002;19(3):249-250.
3. Longo FM, Massa SM. Neuroprotective strategies in Alzheimer's disease. NeuroRx. 2004;1(1):117-127.
4. Kruman II, Culmsee C, Chan SL, et al. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci. 2000;20(18):6920-6926.
5. Kruman II, Kumaravel TS, Lohani A, et al. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. J Neurosci. 2002;22(5):1752-1762.
6. Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev. 2003;(4):CD004514.
7. Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006;5(11):949-960.
8. Wright CB, Paik MC, Brown TR, et al. Total homocysteine is associated with white matter hyperintensity volume: the Northern Manhattan Study. Stroke. 2005;36(6):1207-1211.
9. Selhub J. The many facets of hyperhomocysteinemia: studies from the Framingham cohorts. J Nutr. 2006;136(6)(suppl):1726S-1730S.
10. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol. 1998;55(11):1449-1455.
11. Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002;346(7):476-483.
12. Irizarry MC, Gurol ME, Raju S, et al. Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease. Neurology. 2005;65(9):1402-1408.
13. Luchsinger JA, Tang MX, Miller J, Green R, Mehta PD, Mayeux R. Relation of plasma homocysteine to plasma amyloid beta levels. Neurochem Res. 2007;32(4-5):775-781.
14. Flicker L, Martins RN, Thomas J, et al. B-vitamins reduce plasma levels of beta amyloid [published ahead of print 2006 November 20, 2006]. Neurobiol Aging. 2008;29(2):303-305.
15. Homocysteine Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ. 1998;316(7135):894-898.
16. Aisen PS, Egelko S, Andrews H, et al. A pilot study of vitamins to lower plasma homocysteine levels in Alzheimer disease. Am J Geriatr Psychiatry. 2003;11(2):246-249.
17. Balk EM, Raman G, Tatsioni A, Chung M, Lau J, Rosenberg IH. Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials. Arch Intern Med. 2007;167(1):21-30.
18. Durga J, van Boxtel MP, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007;369(9557):208- 216.
19. McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med. 2006;354(26):2764-2772.
20. Sun Y, Lu CJ, Chien KL, Chen ST, Chen RC. Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients. Clin Ther. 2007;29(10):2204-2214.
21. Connelly PJ, Prentice NP, Cousland G, Bonham J. A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease. Int J Geriatr Psychiatry. 2008;23(2):155-160.
22. Nilsson K, Gustafson L, Hultberg B. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. Int J Geriatr Psychiatry. 2001;16(6):609-614.
23. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group. Neurology. 1984;34(7):939-944.
24. Folstein MF, Folstein SE, McHugh PR. 'Mini-mental state': a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-198.
25. Schaumburg H, Kaplan J, Windebank A, et al. Sensory neuropathy from pyridoxine abuse: a new mega-vitamin syndrome. N Engl J Med. 1983;309(8):445-448.
26. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984;141(11):1356-1364.
27. Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993;43(11):2412-2414.
28. Galasko D, Bennett D, Sano M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. Alzheimer Dis Assoc Disord. 1997;11(suppl 2):S33-S39.
29. Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997;48(5)(suppl 6):S10-S16.
30. Logsdon RG, Gibbons LE, McCurry SM, Teri L. Quality of life in Alzheimer's disease: patient and caregiver reports. J Ment Health Aging. 1999;5:21-32.
31. Aisen PS, Schafer KA, Grundman M, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA. 2003;289(21):2819-2826.
32. Ubbink JB, Vermaak WJ, Bennett JM, Becker PJ, van Staden DA, Bissbort S. The prevalence of homocysteinemia and hypercholesterolemia in angiographically defined coronary heart disease. Klin Wochenschr. 1991;69(12):527-534.
33. Bisp MR, Bor MV, Heinsvig EM, Kall MA, Nexo E. Determination of vitamin B6 vitamers and pyridoxic acid in plasma: development and evaluation of a high-performance liquid chromatographic assay. Anal Biochem. 2002;305(1):82-89.
34. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10(1):111-113.
35. Zeger SL, Liang KY. Longitudinal data analysis for discrete and continuous outcomes. Biometrics. 1986;42(1):121-130.
36. Aisen PS, Davis KL, Berg JD, et al. A randomized controlled trial of prednisone in Alzheimer's disease: Alzheimer's Disease Cooperative Study. Neurology. 2000;54(3):588-593.
37. Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med. 1999;340(19):1449-1454.
38. O'Suilleabhain PE, Sung V, Hernandez C, et al. Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations. Arch Neurol. 2004;61(6):865-868.
39. Folstein M, Liu T, Peter I, et al. The homocysteine hypothesis of depression. Am J Psychiatry. 2007;164(6):861-867.
40. Fava M. Augmenting antidepressants with folate: a clinical perspective. J Clin Psychiatry. 2007;68(suppl 10):4-7.