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Published in: Drugs & Aging 5/2019

01-05-2019 | Folic Acid | Systematic Review

Effect of Vitamin B Supplementation on Cognitive Function in the Elderly: A Systematic Review and Meta-Analysis

Authors: Andrew H. Ford, Osvaldo P. Almeida

Published in: Drugs & Aging | Issue 5/2019

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Abstract

Background

Vitamin B deficiency and elevated total plasma homocysteine have been associated with cognitive impairment and dementia in later life, although it is unknown if treatment with these vitamins improves cognitive outcomes.

Objectives

The objectives of this study were to examine the efficacy of treatment with vitamin B12, vitamin B6, or folic acid in slowing cognitive decline amongst older adults with and without cognitive impairment.

Methods

We summarized findings from previous systematic reviews of clinical trials and performed a new systematic review and meta-analysis of 31 English-language, randomized placebo-controlled trials of B-vitamin supplementation of individuals with and without existing cognitive impairment.

Results

Previous reviews have generally reported no effect of B vitamins on cognitive function in older adults with or without cognitive impairment at study entry, although these vitamins effectively lowered total plasma homocysteine levels in participants. Ten randomized placebo-controlled trials of 1925 participants with pre-existing cognitive impairment and 21 trials of 15,104 participants without cognitive impairment have been completed to date but these generally confirmed findings from previous reviews with the exception of two trials that showed a modest but clinically uncertain benefit for vitamins in people with elevated plasma homocysteine. B-vitamin supplementation did not show an improvement in Mini-Mental State Examination scores for individuals with (mean difference 0.16, 95% confidence interval − 0.18 to 0.51) and without (mean difference 0.04, 95% confidence interval − 0.10 to 0.18) cognitive impairment compared to placebo.

Conclusions

Raised total plasma homocysteine is associated with an increased risk of cognitive impairment and dementia, although available evidence from randomized controlled trials shows no obvious cognitive benefit of lowering homocysteine using B vitamins. Existing trials vary greatly in the type of supplementation, population sampled, study quality, and duration of treatment, thereby making it difficult to draw firm conclusions from existing data. Findings should therefore be viewed in the context of the limitations of the available data and the lack of evidence of effect should not necessarily be interpreted as evidence of no effect.
Literature
1.
go back to reference Wu YT, Beiser AS, Breteler MMB, et al. The changing prevalence and incidence of dementia over time: current evidence. Nat Rev Neurol. 2017;13(6):327–39.CrossRefPubMed Wu YT, Beiser AS, Breteler MMB, et al. The changing prevalence and incidence of dementia over time: current evidence. Nat Rev Neurol. 2017;13(6):327–39.CrossRefPubMed
3.
go back to reference Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673–4.CrossRefPubMed Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673–4.CrossRefPubMed
4.
go back to reference Droller H, Dossett JA. Vitamin B12 levels in senile dementia and confusional states. Geriatrics. 1959;14(6):367–73.PubMed Droller H, Dossett JA. Vitamin B12 levels in senile dementia and confusional states. Geriatrics. 1959;14(6):367–73.PubMed
5.
go back to reference Woltman HW. Brain changes associated with pernicious anemia. Arch Intern Med. 1918;XXI(6):791–843.CrossRef Woltman HW. Brain changes associated with pernicious anemia. Arch Intern Med. 1918;XXI(6):791–843.CrossRef
6.
go back to reference Goebels N, Soyka M. Dementia associated with vitamin B(12) deficiency: presentation of two cases and review of the literature. J Neuropsychiatry Clin Neurosci. 2000;12(3):389–94.CrossRefPubMed Goebels N, Soyka M. Dementia associated with vitamin B(12) deficiency: presentation of two cases and review of the literature. J Neuropsychiatry Clin Neurosci. 2000;12(3):389–94.CrossRefPubMed
7.
go back to reference Ford AH, Flicker L, Hankey GJ, et al. Homocysteine, methylenetetrahydrofolate reductase C677T polymorphism and cognitive impairment: the health in men study. Mol Psychiatry. 2012;17(5):559–66.CrossRefPubMed Ford AH, Flicker L, Hankey GJ, et al. Homocysteine, methylenetetrahydrofolate reductase C677T polymorphism and cognitive impairment: the health in men study. Mol Psychiatry. 2012;17(5):559–66.CrossRefPubMed
8.
go back to reference Smith AD. The worldwide challenge of the dementias: a role for B vitamins and homocysteine? Food Nutr Bull. 2008;29(2 Suppl.):S143–72.CrossRefPubMed Smith AD. The worldwide challenge of the dementias: a role for B vitamins and homocysteine? Food Nutr Bull. 2008;29(2 Suppl.):S143–72.CrossRefPubMed
9.
go back to reference Van Dam F, Van Gool WA. Hyperhomocysteinemia and Alzheimer’s disease: a systematic review. Arch Gerontol Geriatr. 2009;48(3):425–30.CrossRefPubMed Van Dam F, Van Gool WA. Hyperhomocysteinemia and Alzheimer’s disease: a systematic review. Arch Gerontol Geriatr. 2009;48(3):425–30.CrossRefPubMed
10.
go back to reference Homocysteine Lowering Trialists’ Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists’ Collaboration. BMJ. 1998;316(7135):894–8.CrossRef Homocysteine Lowering Trialists’ Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists’ Collaboration. BMJ. 1998;316(7135):894–8.CrossRef
11.
go back to reference Ford AH, Almeida OP. Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. J Alzheimers Dis. 2012;29(1):133–49.CrossRefPubMed Ford AH, Almeida OP. Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. J Alzheimers Dis. 2012;29(1):133–49.CrossRefPubMed
12.
go back to reference 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):189–98.CrossRefPubMed 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):189–98.CrossRefPubMed
13.
14.
go back to reference Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev. 2003;4:CD004514. Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev. 2003;4:CD004514.
15.
go back to reference Malouf R, Areosa Sastre A. Vitamin B12 for cognition. Cochrane Database Syst Rev. 2003;3:CD004326. Malouf R, Areosa Sastre A. Vitamin B12 for cognition. Cochrane Database Syst Rev. 2003;3:CD004326.
16.
go back to reference Malouf R, Grimley Evans J. The effect of vitamin B6 on cognition. Cochrane Database Syst Rev. 2003;4:CD004393. Malouf R, Grimley Evans J. The effect of vitamin B6 on cognition. Cochrane Database Syst Rev. 2003;4:CD004393.
17.
go back to reference Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev. 2008;(4):CD004514. Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev. 2008;(4):CD004514.
18.
go back to reference Wald DS, Kasturiratne A, Simmonds M. Effect of folic acid, with or without other B vitamins, on cognitive decline: meta-analysis of randomized trials. Am J Med. 2010;123(6):522.e2–527.e2.CrossRef Wald DS, Kasturiratne A, Simmonds M. Effect of folic acid, with or without other B vitamins, on cognitive decline: meta-analysis of randomized trials. Am J Med. 2010;123(6):522.e2–527.e2.CrossRef
19.
go back to reference 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):208–16.CrossRefPubMed 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):208–16.CrossRefPubMed
20.
go back to reference Clarke R, Bennett D, Parish S, et al. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. Am J Clin Nutr. 2014;100(2):657–66.CrossRefPubMedPubMedCentral Clarke R, Bennett D, Parish S, et al. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. Am J Clin Nutr. 2014;100(2):657–66.CrossRefPubMedPubMedCentral
21.
go back to reference Li MM, Yu JT, Wang HF, et al. Efficacy of vitamins B supplementation on mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis. Curr Alzheimer Res. 2014;11(9):844–52.PubMed Li MM, Yu JT, Wang HF, et al. Efficacy of vitamins B supplementation on mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis. Curr Alzheimer Res. 2014;11(9):844–52.PubMed
22.
go back to reference Zhang DM, Ye JX, Mu JS, Cui XP. Efficacy of vtamin B supplementation on cognition in elderly patients with cognitive-related diseases. J Geriatr Psychiatry Neurol. 2017;30(1):50–9.CrossRefPubMed Zhang DM, Ye JX, Mu JS, Cui XP. Efficacy of vtamin B supplementation on cognition in elderly patients with cognitive-related diseases. J Geriatr Psychiatry Neurol. 2017;30(1):50–9.CrossRefPubMed
24.
go back to reference Hankey GJ, Ford AH, Yi Q, et al. Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis. Stroke. 2013;44(8):2232–9.CrossRefPubMed Hankey GJ, Ford AH, Yi Q, et al. Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis. Stroke. 2013;44(8):2232–9.CrossRefPubMed
25.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
26.
go back to reference Clarke R, Harrison G, Richards S. Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia. J Intern Med. 2003;254(1):67–75.CrossRefPubMed Clarke R, Harrison G, Richards S. Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia. J Intern Med. 2003;254(1):67–75.CrossRefPubMed
27.
go back to reference 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):155–60.CrossRefPubMed 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):155–60.CrossRefPubMed
28.
go back to reference Kwok T, Lee J, Law CB, et al. A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people. Clin Nutr. 2011;30(3):297–302.CrossRefPubMed Kwok T, Lee J, Law CB, et al. A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people. Clin Nutr. 2011;30(3):297–302.CrossRefPubMed
29.
go back to reference Sommer BR, Hoff AL, Costa M. Folic acid supplementation in dementia: a preliminary report. J Geriatr Psychiatry Neurol. 2003;16(3):156–9.CrossRefPubMed Sommer BR, Hoff AL, Costa M. Folic acid supplementation in dementia: a preliminary report. J Geriatr Psychiatry Neurol. 2003;16(3):156–9.CrossRefPubMed
30.
go back to reference Fioravanti M, Ferrario E, Massaia M, et al. Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits. Arch Gerontol Geriatr. 1998;26(1):1–13.CrossRefPubMed Fioravanti M, Ferrario E, Massaia M, et al. Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits. Arch Gerontol Geriatr. 1998;26(1):1–13.CrossRefPubMed
31.
go back to reference de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. 2012;27(6):592–600.CrossRefPubMed de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. 2012;27(6):592–600.CrossRefPubMed
32.
go back to reference Ting SKS, Earnest A, Li H, et al. B vitamins and cognition in subjects with small vessel disease: a substudy of VITATOPS, a randomized, placebo-controlled trial. J Neurol Sci. 2017;379:124–6.CrossRefPubMed Ting SKS, Earnest A, Li H, et al. B vitamins and cognition in subjects with small vessel disease: a substudy of VITATOPS, a randomized, placebo-controlled trial. J Neurol Sci. 2017;379:124–6.CrossRefPubMed
33.
go back to reference van Uffelen JG, Chinapaw MJ, van Mechelen W, Hopman-Rock M. Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial. Br J Sports Med. 2008;42(5):344–51.CrossRefPubMed van Uffelen JG, Chinapaw MJ, van Mechelen W, Hopman-Rock M. Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial. Br J Sports Med. 2008;42(5):344–51.CrossRefPubMed
34.
go back to reference Bryan J, Calvaresi E, Hughes D. Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages. J Nutr. 2002;132(6):1345–56.CrossRefPubMed Bryan J, Calvaresi E, Hughes D. Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages. J Nutr. 2002;132(6):1345–56.CrossRefPubMed
35.
go back to reference Cheng D, Kong H, Pang W, et al. B vitamin supplementation improves cognitive function in the middle aged and elderly with hyperhomocysteinemia. Nutr Neurosci. 2016;19(10):461–6.CrossRefPubMed Cheng D, Kong H, Pang W, et al. B vitamin supplementation improves cognitive function in the middle aged and elderly with hyperhomocysteinemia. Nutr Neurosci. 2016;19(10):461–6.CrossRefPubMed
36.
go back to reference Deijen JB, van der Beek EJ, Orlebeke JF, van den Berg H. Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance and mental effort. Psychopharmacology. 1992;109(4):489–96.CrossRefPubMed Deijen JB, van der Beek EJ, Orlebeke JF, van den Berg H. Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance and mental effort. Psychopharmacology. 1992;109(4):489–96.CrossRefPubMed
37.
go back to reference Eussen SJ, de Groot LC, Joosten LW, et al. Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial. Am J Clin Nutr. 2006;84(2):361–70.CrossRefPubMed Eussen SJ, de Groot LC, Joosten LW, et al. Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial. Am J Clin Nutr. 2006;84(2):361–70.CrossRefPubMed
38.
go back to reference Ford AH, Flicker L, Alfonso H, et al. Vitamins B(12), B(6), and folic acid for cognition in older men. Neurology. 2010;75(17):1540–7.CrossRefPubMed Ford AH, Flicker L, Alfonso H, et al. Vitamins B(12), B(6), and folic acid for cognition in older men. Neurology. 2010;75(17):1540–7.CrossRefPubMed
39.
go back to reference Hvas AM, Juul S, Lauritzen L, Nexo E, Ellegaard J. No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. J Affect Disord. 2004;81(3):269–73.CrossRefPubMed Hvas AM, Juul S, Lauritzen L, Nexo E, Ellegaard J. No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. J Affect Disord. 2004;81(3):269–73.CrossRefPubMed
40.
go back to reference Kang JH, Cook N, Manson J, et al. A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am J Clin Nutr. 2008;88(6):1602–10.CrossRefPubMed Kang JH, Cook N, Manson J, et al. A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am J Clin Nutr. 2008;88(6):1602–10.CrossRefPubMed
41.
go back to reference Lewerin C, Matousek M, Steen G, et al. Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo-controlled randomized study. Am J Clin Nutr. 2005;81(5):1155–62.CrossRefPubMed Lewerin C, Matousek M, Steen G, et al. Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo-controlled randomized study. Am J Clin Nutr. 2005;81(5):1155–62.CrossRefPubMed
42.
go back to reference McMahon JA, Green TJ, Skeaff CM, et al. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med. 2006;354(26):2764–72.CrossRefPubMed McMahon JA, Green TJ, Skeaff CM, et al. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med. 2006;354(26):2764–72.CrossRefPubMed
43.
go back to reference Pathansali R, Mangoni AA, Creagh-Brown B, et al. Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects. Arch Gerontol Geriatr. 2006;43(1):127–37.CrossRefPubMed Pathansali R, Mangoni AA, Creagh-Brown B, et al. Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects. Arch Gerontol Geriatr. 2006;43(1):127–37.CrossRefPubMed
44.
go back to reference Walker JG, Batterham PJ, Mackinnon AJ, et al. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms: the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr. 2012;95(1):194–203.CrossRefPubMed Walker JG, Batterham PJ, Mackinnon AJ, et al. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms: the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr. 2012;95(1):194–203.CrossRefPubMed
45.
go back to reference Andreeva VA, Kesse-Guyot E, Barberger-Gateau P, et al. Cognitive function after supplementation with B vitamins and long-chain omega-3 fatty acids: ancillary findings from the SU.FOL.OM3 randomized trial. Am J Clin Nutr. 2011;94(1):278–86. Andreeva VA, Kesse-Guyot E, Barberger-Gateau P, et al. Cognitive function after supplementation with B vitamins and long-chain omega-3 fatty acids: ancillary findings from the SU.FOL.OM3 randomized trial. Am J Clin Nutr. 2011;94(1):278–86.
46.
go back to reference Brady CB, Gaziano JM, Cxypoliski RA, et al. Homocysteine lowering and cognition in CKD: the Veterans Affairs homocysteine study. Am J Kidney Dis. 2009;54(3):440–9.CrossRefPubMedPubMedCentral Brady CB, Gaziano JM, Cxypoliski RA, et al. Homocysteine lowering and cognition in CKD: the Veterans Affairs homocysteine study. Am J Kidney Dis. 2009;54(3):440–9.CrossRefPubMedPubMedCentral
47.
go back to reference Dangour AD, Allen E, Clarke R, et al. Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial. Am J Clin Nutr. 2015;102(3):639–47.CrossRefPubMedPubMedCentral Dangour AD, Allen E, Clarke R, et al. Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial. Am J Clin Nutr. 2015;102(3):639–47.CrossRefPubMedPubMedCentral
48.
go back to reference Kwok T, Lee J, Ma RC, et al. A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12. Clin Nutr. 2017;36(6):1509–15.CrossRefPubMed Kwok T, Lee J, Ma RC, et al. A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12. Clin Nutr. 2017;36(6):1509–15.CrossRefPubMed
49.
go back to reference Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354(15):1567–77.CrossRefPubMed Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354(15):1567–77.CrossRefPubMed
50.
go back to reference Seal EC, Metz J, Flicker L, Melny J. A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. J Am Geriatr Soc. 2002;50(1):146–51.CrossRefPubMed Seal EC, Metz J, Flicker L, Melny J. A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. J Am Geriatr Soc. 2002;50(1):146–51.CrossRefPubMed
51.
go back to reference Stott DJ, MacIntosh G, Lowe GD, et al. Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease. Am J Clin Nutr. 2005;82(6):1320–6.CrossRefPubMed Stott DJ, MacIntosh G, Lowe GD, et al. Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease. Am J Clin Nutr. 2005;82(6):1320–6.CrossRefPubMed
52.
go back to reference Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group, Armitage JM, Bowman L, Clarke RJ, Wallendszus K, Bulbulia R, et al. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA. 2010;303(24):2486–94. Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group, Armitage JM, Bowman L, Clarke RJ, Wallendszus K, Bulbulia R, et al. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA. 2010;303(24):2486–94.
53.
go back to reference Garcia A, Pulman K, Zanibbi K, et al. Cobalamin reduces homocysteine in older adults on folic acid-fortified diet: a pilot, double-blind, randomized, placebo-controlled trial. J Am Geriatr Soc. 2004;52(8):1410–2.CrossRefPubMed Garcia A, Pulman K, Zanibbi K, et al. Cobalamin reduces homocysteine in older adults on folic acid-fortified diet: a pilot, double-blind, randomized, placebo-controlled trial. J Am Geriatr Soc. 2004;52(8):1410–2.CrossRefPubMed
55.
56.
go back to reference Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010;5(9):e12244.CrossRefPubMedPubMedCentral Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010;5(9):e12244.CrossRefPubMedPubMedCentral
57.
go back to reference Group VTS. B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol. 2010;9(9):855–65.CrossRef Group VTS. B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol. 2010;9(9):855–65.CrossRef
58.
go back to reference Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett. 2006;580(13):2994–3005.CrossRefPubMed Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett. 2006;580(13):2994–3005.CrossRefPubMed
59.
go back to reference Vafai SB, Stock JB. Protein phosphatase 2A methylation: a link between elevated plasma homocysteine and Alzheimer’s disease. FEBS Lett. 2002;518(1–3):1–4.CrossRefPubMed Vafai SB, Stock JB. Protein phosphatase 2A methylation: a link between elevated plasma homocysteine and Alzheimer’s disease. FEBS Lett. 2002;518(1–3):1–4.CrossRefPubMed
60.
go back to reference Sai X, Kawamura Y, Kokame K, et al. Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein. J Biol Chem. 2002;277(15):12915–20.CrossRefPubMed Sai X, Kawamura Y, Kokame K, et al. Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein. J Biol Chem. 2002;277(15):12915–20.CrossRefPubMed
61.
go back to reference Xu D, Neville R, Finkel T. Homocysteine accelerates endothelial cell senescence. FEBS Lett. 2000;470(1):20–4.CrossRefPubMed Xu D, Neville R, Finkel T. Homocysteine accelerates endothelial cell senescence. FEBS Lett. 2000;470(1):20–4.CrossRefPubMed
62.
go back to reference Orentreich N, Matias JR, DeFelice A, Zimmerman JA. Low methionine ingestion by rats extends life span. J Nutr. 1993;123(2):269–74.PubMed Orentreich N, Matias JR, DeFelice A, Zimmerman JA. Low methionine ingestion by rats extends life span. J Nutr. 1993;123(2):269–74.PubMed
63.
go back to reference Smith AD, Refsum H. Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr. 2016;36:211–39.CrossRefPubMed Smith AD, Refsum H. Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr. 2016;36:211–39.CrossRefPubMed
64.
go back to reference Ho RC, Cheung MW, Fu E, et al. Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression. Am J Geriatr Psychiatry. 2011;19(7):607–17.CrossRefPubMed Ho RC, Cheung MW, Fu E, et al. Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression. Am J Geriatr Psychiatry. 2011;19(7):607–17.CrossRefPubMed
65.
go back to reference 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):111–3.CrossRefPubMed 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):111–3.CrossRefPubMed
66.
go back to reference Ford AH, Flicker L, Alfonso H, et al. Plasma homocysteine and MTHFRC677T polymorphism as risk factors for incident dementia. J Neurol Neurosurg Psychiatry. 2012;83(1):70–5.CrossRefPubMed Ford AH, Flicker L, Alfonso H, et al. Plasma homocysteine and MTHFRC677T polymorphism as risk factors for incident dementia. J Neurol Neurosurg Psychiatry. 2012;83(1):70–5.CrossRefPubMed
67.
go back to reference Hu Q, Teng W, Li J, Hao F, Wang N. Homocysteine and Alzheimer’s disease: evidence for a causal link from Mendelian randomization. J Alzheimers Dis. 2016;52(2):747–56.CrossRefPubMed Hu Q, Teng W, Li J, Hao F, Wang N. Homocysteine and Alzheimer’s disease: evidence for a causal link from Mendelian randomization. J Alzheimers Dis. 2016;52(2):747–56.CrossRefPubMed
68.
go back to reference Holmes MV, Newcombe P, Hubacek JA, et al. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet. 2011;378(9791):584–94.CrossRefPubMedPubMedCentral Holmes MV, Newcombe P, Hubacek JA, et al. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet. 2011;378(9791):584–94.CrossRefPubMedPubMedCentral
Metadata
Title
Effect of Vitamin B Supplementation on Cognitive Function in the Elderly: A Systematic Review and Meta-Analysis
Authors
Andrew H. Ford
Osvaldo P. Almeida
Publication date
01-05-2019
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 5/2019
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.1007/s40266-019-00649-w

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