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High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial.
JAMA 2008; 300(15):1774-83JAMA

Abstract

CONTEXT

Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B(6) and B(12). Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline.

OBJECTIVE

To determine the efficacy and safety of B vitamin supplementation in the treatment of AD.

DESIGN, SETTING, AND PATIENTS

A multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B(6), and vitamin B(12) supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B(12), and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States.

INTERVENTION

Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B(6), 1 mg/d of vitamin B(12)] and 40% treated with identical placebo); duration of treatment was 18 months.

MAIN OUTCOME MEASURE

Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog).

RESULTS

A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], -2.42 [3.35] in active treatment group vs -0.86 [2.59] in placebo group; P < .001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-cog score during 18 months (0.372 points per month for placebo group vs 0.401 points per month for active treatment group, P = .52; 95% confidence interval of rate difference, -0.06 to 0.12; based on the intention-to-treat generalized estimating equations model), or on any secondary measures. A higher quantity of adverse events involving depression was observed in the group treated with vitamin supplements.

CONCLUSION

This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT00056225.

Authors+Show Affiliations

Department of Neurosciences, University of California, San Diego, 9500 Gilman Dr, M/C 0949, La Jolla, CA 92093, USA. paisen@ucsd.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18854539

Citation

Aisen, Paul S., et al. "High-dose B Vitamin Supplementation and Cognitive Decline in Alzheimer Disease: a Randomized Controlled Trial." JAMA, vol. 300, no. 15, 2008, pp. 1774-83.
Aisen PS, Schneider LS, Sano M, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008;300(15):1774-83.
Aisen, P. S., Schneider, L. S., Sano, M., Diaz-Arrastia, R., van Dyck, C. H., Weiner, M. F., ... Thal, L. J. (2008). High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA, 300(15), pp. 1774-83. doi:10.1001/jama.300.15.1774.
Aisen PS, et al. High-dose B Vitamin Supplementation and Cognitive Decline in Alzheimer Disease: a Randomized Controlled Trial. JAMA. 2008 Oct 15;300(15):1774-83. PubMed PMID: 18854539.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. AU - Aisen,Paul S, AU - Schneider,Lon S, AU - Sano,Mary, AU - Diaz-Arrastia,Ramon, AU - van Dyck,Christopher H, AU - Weiner,Myron F, AU - Bottiglieri,Teodoro, AU - Jin,Shelia, AU - Stokes,Karen T, AU - Thomas,Ronald G, AU - Thal,Leon J, AU - ,, PY - 2008/10/16/pubmed PY - 2008/10/22/medline PY - 2008/10/16/entrez SP - 1774 EP - 83 JF - JAMA JO - JAMA VL - 300 IS - 15 N2 - CONTEXT: Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B(6) and B(12). Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline. OBJECTIVE: To determine the efficacy and safety of B vitamin supplementation in the treatment of AD. DESIGN, SETTING, AND PATIENTS: A multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B(6), and vitamin B(12) supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B(12), and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States. INTERVENTION: Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B(6), 1 mg/d of vitamin B(12)] and 40% treated with identical placebo); duration of treatment was 18 months. MAIN OUTCOME MEASURE: Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). RESULTS: A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], -2.42 [3.35] in active treatment group vs -0.86 [2.59] in placebo group; P < .001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-cog score during 18 months (0.372 points per month for placebo group vs 0.401 points per month for active treatment group, P = .52; 95% confidence interval of rate difference, -0.06 to 0.12; based on the intention-to-treat generalized estimating equations model), or on any secondary measures. A higher quantity of adverse events involving depression was observed in the group treated with vitamin supplements. CONCLUSION: This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056225. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/18854539/High_dose_B_vitamin_supplementation_and_cognitive_decline_in_Alzheimer_disease:_a_randomized_controlled_trial_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.300.15.1774 DB - PRIME DP - Unbound Medicine ER -