Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
17
04
2023
accepted:
25
04
2023
medline:
27
7
2023
pubmed:
13
5
2023
entrez:
13
5
2023
Statut:
ppublish
Résumé
The association between markers of vitamin B12 status and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), which precede cognitive impairment, has been investigated by only a few small studies and results have been inconsistent. The aim of this study was to investigate the associations of vitamin B12-related markers with CSF biomarkers of AD and cognitive performance. Data included 462 patients aged 40 to 94 years referred to the Memory Clinic of the Ulm University Hospital, Ulm, Germany. Vitamin B12, holotranscobalamin (HoloTC), homocysteine (tHcy), and methylmalonic acid (MMA) have been measured. CSF values of amyloid β In the multi-adjusted model, higher levels of MMA were associated with raised CSF total-tau values: the odds ratios (ORs) 95% confidence intervals (CIs) were 3.25 (95% CI = 1.35-7.76) for the highest quartile of MMA compared to the lowest. Furthermore, moderately increased MMA were related to lower Aβ Markers of vitamin B12 may be independent predictors of CSF biomarkers of AD and cognitive functioning, with MMA showing the most consistent effects. Randomized controlled trials are needed to determine the importance of vitamin B12 supplementation on slowing structural brain changes and cognitive decline. ANN NEUROL 2023;94:223-231.
Sections du résumé
BACKGROUND
The association between markers of vitamin B12 status and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), which precede cognitive impairment, has been investigated by only a few small studies and results have been inconsistent.
AIM
The aim of this study was to investigate the associations of vitamin B12-related markers with CSF biomarkers of AD and cognitive performance.
METHODS
Data included 462 patients aged 40 to 94 years referred to the Memory Clinic of the Ulm University Hospital, Ulm, Germany. Vitamin B12, holotranscobalamin (HoloTC), homocysteine (tHcy), and methylmalonic acid (MMA) have been measured. CSF values of amyloid β
RESULTS
In the multi-adjusted model, higher levels of MMA were associated with raised CSF total-tau values: the odds ratios (ORs) 95% confidence intervals (CIs) were 3.25 (95% CI = 1.35-7.76) for the highest quartile of MMA compared to the lowest. Furthermore, moderately increased MMA were related to lower Aβ
CONCLUSIONS
Markers of vitamin B12 may be independent predictors of CSF biomarkers of AD and cognitive functioning, with MMA showing the most consistent effects. Randomized controlled trials are needed to determine the importance of vitamin B12 supplementation on slowing structural brain changes and cognitive decline. ANN NEUROL 2023;94:223-231.
Substances chimiques
Vitamin B 12
P6YC3EG204
Amyloid beta-Peptides
0
Biomarkers
0
Methylmalonic Acid
8LL8S712J7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
223-231Informations de copyright
© 2023 American Neurological Association.
Références
Hooshmand B, Mangialasche F, Kalpouzos G, et al. Association of vitamin B12, folate, and sulfur amino acids with brain magnetic resonance imaging measures in older adults: a longitudinal population-based study. JAMA Psychiat 2016;73:606-613.
Vogiatzoglou A, Refsum H, Johnston C, et al. Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology 2008;71:826-832.
Hooshmand B, Solomon A, Kareholt I, et al. Associations between serum homocysteine, holotranscobalamin, folate and cognition in the elderly: a longitudinal study. J Intern Med 2012;271:204-212.
Smith AD, Warren MJ, Refsum H. Vitamin B12. Adv Food Nutr Res 2018;83:215-279.
Zhang C, Luo J, Yuan C, Ding D. Vitamin B12, B6, or folate and cognitive function in community-dwelling older adults: a systematic review and meta-analysis. J Alzheimers Dis 2020;77:781-794.
Scheltens P, De Strooper B, Kivipelto M, et al. Alzheimer's disease. Lancet 2021;397:1577-1590.
Hooshmand B, Polvikoski T, Kivipelto M, et al. Plasma homocysteine, Alzheimer and cerebrovascular pathology: a population-based autopsy study. Brain 2013;136:2707-2716.
Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett 2006;580:2994-3005.
Flicker L, Martins RN, Thomas J, et al. Homocysteine, Alzheimer genes and proteins, and measures of cognition and depression in older men. J Alzheimers Dis 2004;6:329-336.
Obeid R, Kasoha M, Knapp JP, et al. Folate and methylation status in relation to phosphorylated tau protein (181P) and beta-amyloid (1-42) in cerebrospinal fluid. Clin Chem 2007;53:1129-1136.
Irizarry MC, Gurol ME, Raju S, et al. Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease. Neurology 2005;65:1402-1408.
Luchsinger JA, Tang MX, Miller J, et al. Relation of plasma homocysteine to plasma amyloid beta levels. Neurochem Res 2007;32:775-781.
Popp J, Lewczuk P, Linnebank M, et al. Homocysteine metabolism and cerebrospinal fluid markers for Alzheimer's disease. J Alzheimers Dis 2009;18:819-828.
Alexopoulos P, Gunther F, Popp J, et al. Plasma homocysteine and cerebrospinal fluid neurodegeneration biomarkers in mild cognitive impairment and dementia. J Am Geriatr Soc 2009;57:737-739.
Smach MA, Jacob N, Golmard JL, et al. Folate and homocysteine in the cerebrospinal fluid of patients with Alzheimer's disease or dementia: a case control study. Eur Neurol 2011;65:270-278.
Yetley EA, Pfeiffer CM, Phinney KW, et al. Biomarkers of vitamin B-12 status in NHANES: a roundtable summary. Am J Clin Nutr 2011;94:313S-321S.
Morris JC, Heyman A, Mohs RC, et al. The consortium to establish a registry for Alzheimer's disease (CERAD). Part I. clinical and neuropsychological assessment of Alzheimer's disease. Neurology 1989;39:1159-1165.
Frohlich S, Muller K, Voelcker-Rehage C. Normative data for the CERAD-NP for healthy high-agers (80-84 years) and effects of age-typical visual impairment and hearing loss. J Int Neuropsychol Soc 2021;1-13.
Blennow K, Chen C, Cicognola C, et al. Cerebrospinal fluid tau fragment correlates with tau PET: a candidate biomarker for tangle pathology. Brain 2020;143:650-660.
Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 2010;6:131-144.
Xu H, Wang S, Gao F, Li C. Vitamin B6, B9, and B12 intakes and cognitive performance in elders: National Health and nutrition examination survey, 2011-2014. Neuropsychiatr Dis Treat 2022;18:537-553.
Sala I, Belen Sanchez-Saudinos M, Molina-Porcel L, et al. Homocysteine and cognitive impairment. Relation with diagnosis and neuropsychological performance. Dement Geriatr Cogn Disord 2008;26:506-512.
Oikonomidi A, Lewczuk P, Kornhuber J, et al. Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta. J Neurochem 2016;139:324-332.
Dayon L, Guiraud SP, Corthesy J, et al. One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond. Alzheimers Res Ther 2017;9:43.
Hooper C, de Souto BP, Coley N, et al. Cross-sectional associations of Total plasma homocysteine with cortical beta-amyloid independently and as a function of omega 3 polyunsaturated fatty acid status in older adults at risk of dementia. J Nutr Health Aging 2017;21:1075-1080.
Byeon G, Byun MS, Yi D, et al. Synergistic effect of serum homocysteine and diabetes mellitus on brain alterations. J Alzheimers Dis 2021;81:287-295.
Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med 2013;368:149-160.
Sobczynska-Malefora A, Smith AD. Vitamin B-12. Adv Nutr 2022;13:2061-2063.
Hvas AM, Nexo E. Holotranscobalamin-a first choice assay for diagnosing early vitamin B deficiency? J Intern Med 2005;257:289-298.
Green R, Miller JW. Vitamin B12 deficiency. Vitam Horm 2022;119:405-439.
de Almeida LM, Funchal C, Pelaez Pde L, et al. Effect of propionic and methylmalonic acids on the in vitro phosphorylation of intermediate filaments from cerebral cortex of rats during development. Metab Brain Dis 2003;18:207-219.
Obeid R, Schadt A, Dillmann U, et al. Methylation status and neurodegenerative markers in Parkinson disease. Clin Chem 2009;55:1852-1860.
Tangney CC, Aggarwal NT, Li H, et al. Vitamin B12, cognition, and brain MRI measures: a cross-sectional examination. Neurology 2011;77:1276-1282.
Scarmeas N, Anastasiou CA, Yannakoulia M. Nutrition and prevention of cognitive impairment. Lancet Neurol 2018;17:1006-1015.
Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet 2017;390:2673-2734.
Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the lancet commission. Lancet 2020;396:413-446.
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:e12244.
Douaud G, Refsum H, de Jager CA, et al. Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci USA 2013;110:9523-9528.