Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance

Babak Hooshmand; Franziska Appold; Patrick Fissler; Robert Perneczky; Markus Otto; Hayrettin Tumani; Miia Kivipelto; Christine A F von Arnim

doi:10.1002/ana.26673

Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance

Babak Hooshmand
, Franziska Appold
, Patrick Fissler
, Robert Perneczky
, Markus Otto
, Hayrettin Tumani
, Miia Kivipelto
, Christine A F von Arnim

Karolinska Institute and Karolinska University Hospital
University Hospital of Ulm
University Hospital Munich (LMU)
University Hospital Halle (Saale)
Vanderbilt University Medical Center

Research output: Contribution to journal › Original Article › peer-review

Abstract

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 β42 (Aβ42 ) and total-tau have been assessed in 227 participants. CERAD battery was administered to examine the cognitive status, and different domains were derived. Regression models were used to investigate the associations.

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 Aβ42 levels: the ORs and 95% CIs were 3.06 (95% CI = 1.22-7.67) for the third quartile of MMA compared to the lowest. All B12 indicators except B12 itself were related to several cognitive domains, such as episodic memory and executive functioning.

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.

Original language	English
Pages (from-to)	223-231
Number of pages	9
Journal	ANNALS OF NEUROLOGY
Volume	94
Issue number	2
DOIs	https://doi.org/10.1002/ana.26673
Publication status	Published - Aug 2023

Keywords

Humans
Vitamin B 12
Alzheimer Disease/diagnosis
Amyloid beta-Peptides
Vitamin B 12 Deficiency/complications
Biomarkers
Cognition
Cognitive Dysfunction/diagnosis
Methylmalonic Acid

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10.1002/ana.26673

Cite this

Hooshmand, B., Appold, F., Fissler, P., Perneczky, R., Otto, M., Tumani, H., Kivipelto, M., & von Arnim, C. A. F. (2023). Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance. ANNALS OF NEUROLOGY , 94(2), 223-231. https://doi.org/10.1002/ana.26673

Hooshmand, Babak ; Appold, Franziska ; Fissler, Patrick et al. / Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance. In: ANNALS OF NEUROLOGY 2023 ; Vol. 94, No. 2. pp. 223-231.

@article{9845512257604285a288a96c0ea369f6,

title = "Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance",

abstract = "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 β42 (Aβ42 ) and total-tau have been assessed in 227 participants. CERAD battery was administered to examine the cognitive status, and different domains were derived. Regression models were used to investigate the associations.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 Aβ42 levels: the ORs and 95\% CIs were 3.06 (95\% CI = 1.22-7.67) for the third quartile of MMA compared to the lowest. All B12 indicators except B12 itself were related to several cognitive domains, such as episodic memory and executive functioning.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.",

keywords = "Humans, Vitamin B 12, Alzheimer Disease/diagnosis, Amyloid beta-Peptides, Vitamin B 12 Deficiency/complications, Biomarkers, Cognition, Cognitive Dysfunction/diagnosis, Methylmalonic Acid",

author = "Babak Hooshmand and Franziska Appold and Patrick Fissler and Robert Perneczky and Markus Otto and Hayrettin Tumani and Miia Kivipelto and \{von Arnim\}, \{Christine A F\}",

note = "Lehr-kH Psychiatric Services Thurgau, M{\"u}nsterlingen, Switzerland",

year = "2023",

month = aug,

doi = "10.1002/ana.26673",

language = "English",

volume = "94",

pages = "223--231",

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}

Hooshmand, B, Appold, F, Fissler, P, Perneczky, R, Otto, M, Tumani, H, Kivipelto, M & von Arnim, CAF 2023, 'Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance', ANNALS OF NEUROLOGY , vol. 94, no. 2, pp. 223-231. https://doi.org/10.1002/ana.26673

Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance. / Hooshmand, Babak; Appold, Franziska; Fissler, Patrick et al.
In: ANNALS OF NEUROLOGY , Vol. 94, No. 2, 08.2023, p. 223-231.

Research output: Contribution to journal › Original Article › peer-review

TY - JOUR

T1 - Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance

AU - Hooshmand, Babak

AU - Appold, Franziska

AU - Fissler, Patrick

AU - Perneczky, Robert

AU - Otto, Markus

AU - Tumani, Hayrettin

AU - Kivipelto, Miia

AU - von Arnim, Christine A F

N1 - Lehr-kH Psychiatric Services Thurgau, Münsterlingen, Switzerland

PY - 2023/8

Y1 - 2023/8

N2 - 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 β42 (Aβ42 ) and total-tau have been assessed in 227 participants. CERAD battery was administered to examine the cognitive status, and different domains were derived. Regression models were used to investigate the associations.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 Aβ42 levels: the ORs and 95% CIs were 3.06 (95% CI = 1.22-7.67) for the third quartile of MMA compared to the lowest. All B12 indicators except B12 itself were related to several cognitive domains, such as episodic memory and executive functioning.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.

AB - 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 β42 (Aβ42 ) and total-tau have been assessed in 227 participants. CERAD battery was administered to examine the cognitive status, and different domains were derived. Regression models were used to investigate the associations.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 Aβ42 levels: the ORs and 95% CIs were 3.06 (95% CI = 1.22-7.67) for the third quartile of MMA compared to the lowest. All B12 indicators except B12 itself were related to several cognitive domains, such as episodic memory and executive functioning.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.

KW - Humans

KW - Vitamin B 12

KW - Alzheimer Disease/diagnosis

KW - Amyloid beta-Peptides

KW - Vitamin B 12 Deficiency/complications

KW - Biomarkers

KW - Cognition

KW - Cognitive Dysfunction/diagnosis

KW - Methylmalonic Acid

U2 - 10.1002/ana.26673

DO - 10.1002/ana.26673

M3 - Original Article

C2 - 37177814

SN - 0364-5134

VL - 94

SP - 223

EP - 231

JO - ANNALS OF NEUROLOGY

JF - ANNALS OF NEUROLOGY

IS - 2

ER -

Hooshmand B, Appold F, Fissler P, Perneczky R, Otto M, Tumani H et al. Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance. ANNALS OF NEUROLOGY . 2023 Aug;94(2):223-231. doi: 10.1002/ana.26673

Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance

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