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. 2013 Nov 1;13(23):1–45.

Table A1. Systematic Reviews of Treatment with B12 for Cognitive Function.

Author, Year Question (Sources Searched/Dates) Studies Where B12 was Part of Treatment Arm Study Included in this EBA? Vitamin B12 Deficient? Cognitive Impairment or Dementia? Duration of Study (Months) Overall Conclusion
Ford and Almeida, 2012 (44) What is the efficacy of treatment with vitamins B12, B6, or folate in slowing cognitive decline among older adults with and without cognitive impairment? (PubMed, PsychINFO, Embase, Cochrane/to 2011) Aisen et al, 2008 (51) No No Yes (mild to moderate AD) 18 No difference in cognitive function whether receiving vitamin B12 supplementation or not
Clarke et al, 2003 (59) No No Yes (mild to moderate dementia) 3
De Jager et al, 2012 (48) No No Yes (mild cognitive impairment) 24
Kwok et al, 2011 (49) No No Yes (mild to moderate AD or vascular dementia) 24
Garcia et al, 2004 (57) No No No 6
Hvas et al, 2004 (58) No Likely (increased MMA implies low B12) Mixed (1/3 cognitive impairment) 3
Eussen et al, 2006 (53) No Yes (100–200 pmol/L) Mixed (40% mild-moderate cognitive impairment); results not stratified for patients with cognitive impairment 6
Ford et al, 2010 (50) No Not reported Unclear 24
Kang et al, 2008 (52) No Not reported Not reported at baseline 60
Seal et al, 2002 (61) No Yes (100–150 pmol/L) Mixed (1/3 cognitive impairment); results not stratified for patients with cognitive impairment 1
Lewerin et al, 2005 (55) No No Unclear 4
McMahon et al, 2006 (54) No Likely (high Hcy implies low B12) No 24
Stott et al, 2005 (56) No No Mixed (mild or moderate cognitive impairment included) 12
Jia et al, 2008 (45) What is effect of nutrient supplementation on cognitive function in people aged ≥ 65 years? (MEDLINE, Embase/ to 2006) De la Fourniere et al, 1997 (63) No (full study in French, N = 11) Yes (< 178 pmol/L) Yes (all AD) Not reported No difference in cognitive function whether receiving vitamin B12 supplementation or not
Kwok et al, 1998 (62) No Yes (< 120 pmol/L) Mixed (20% with dementia); results not stratified for patients with dementia 4
Bryan et al, 2002 (60) No Not reported No 1
Seal et al, 2002 (61) No Yes (100–150 pmol/L) Mixed (1/3 cognitive impairment); results not stratified for patients with cognitive impairment 1
Clarke et al, 2003 (59) No No Yes (mild to moderate dementia) 3
Lewerin et al, 2005 (55) No No Unclear 4
Stott et al, 2005 (56) No No Mixed (mild or moderate cognitive impairment included) 12
Eussen et al, 2006 (53) No Yes (100–200 pmol/L) Mixed (40% mild to moderate cognitive impairment); results not stratified for patients with cognitive impairment 6
McMahon et al, 2006 (54) No Likely (high Hcy implies low B12) No 24
Balk et al, 2007 (46) Does supplementation with vitamins B6, B12, and folic acid prevent or decrease progression of neurologic changes associated with dementia? (MEDLINE, Commonwealth Agricultural Bureau/to 2005) Hvas et al, 2004 (58) No Likely (increased MMA implies low B12) Mixed (1/3 cognitive impairment) 3 No difference in cognitive function whether receiving vitamin B12 supplementation or not
Eussen et al, 2006 (53) No Yes (100–200 pmol/L) Mixed (40% mild-moderate cognitive impairment); results not stratified for patients with cognitive impairment 6
Bryan et al, 2002 (60) No Not reported No 1
Seal et al, 2002 (61) No Yes (100–150 pmol/L) Mixed (1/3 cognitive impairment); results not stratified for patients with cognitive impairment 1
Kwok et al, 1998 (62) No Yes (< 120 pmol/L) Mixed (20% with dementia); results not stratified for patients with dementia 3
Kral et al, 1970 (64) No (outdated) N/A N/A N/A
Malouf and Areosa, 2003 (Cochrane Review) (47) What is effect of vitamin B12 supplementation on cognitive function of demented and elderly healthy people in terms of preventing the onset or progression of cognitive impairment? (MEDLINE, Embase, Cochrane/to 2006) Hvas et al, 2004 (58) No Likely (increased MMA implies low B12) Mixed (1/3 cognitive impairment) 3 No difference in cognitive function whether receiving vitamin B12 supplementation or not
Seal et al, 2002 (61) No Yes (100–150 pmol/L) Mixed (1/3 cognitive impairment); results not stratified for patients with cognitive impairment 1
De la Fourniere et al, 1997 (63) No (full study in French, N = 11) Yes (< 178 pmol/L) Yes (all AD) Not reported

Abbreviations: AD, Alzheimer disease; EBA, evidence-based analysis; Hcy, homocysteine; MMA, methylmalonic acid.