TY - JOUR

T1 - Vitamin B12 concentration, memory performance, and hippocampal structure in patients with mild cognitive impairment

AU - Köbe, Theresa

AU - Witte, A Veronica

AU - Schnelle, Ariane

AU - Grittner, Ulrike

AU - Tesky, Valentina A

AU - Pantel, Johannes

AU - Schuchardt, Jan Philipp

AU - Hahn, Andreas

AU - Bohlken, Jens

AU - Rujescu, Dan

AU - Flöel, Agnes

N1 - Funding Information: Supported by the Deutsche Forschungsgemeinschaft (grants Fl 379-8/1, Fl 379-10/1; Fl 379-11/1, and DFG-Exc 257) and the Bundesministerium für Bildung und Forschung (grants FKZ 0315673A, 01EO0801, 01GQ1424A, and 01GQ1420B).

PY - 2016/4

Y1 - 2016/4

N2 - BACKGROUND: Low-normal concentrations of vitamin B-12 (VitB12) may be associated with worse cognition. However, previous evidence has been mixed, and the underlying mechanisms remain unclear.OBJECTIVE: We determined whether serum VitB12 concentrations within the normal range were linked to memory functions and related neuronal structures in patients with mild cognitive impairment (MCI).DESIGN: In a cross-sectional design, we assessed 100 amnestic MCI patients (52 women; age range: 50-80 y) with low- and high-normal VitB12 concentration (median split: 304 pmol/L) for memory functions with the use of the Auditory Verbal Learning Test. MRI was performed at 3 tesla (n= 86) for the estimation of the volume and microstructure of the hippocampus and its subfields as indicated by the mean diffusivity on diffusion-weighted images. With the use of a mediation analysis, we examined whether the relation between VitB12 and memory performance was partially explained by volume or microstructure.RESULTS: MCI patients with low-normal VitB12 showed a significantly poorer learning ability (P= 0.014) and recognition performance (P= 0.008) than did patients with high-normal VitB12. Also, the microstructure integrity of the hippocampus was lower in patients with low-normal VitB12, mainly in the cornu ammonis 4 and dentate gyrus region (P= 0.029), which partially mediated the effect of VitB12 on memory performance (32-48%). Adjustments for age, sex, education, apolipoprotein E e4 status, and total homocysteine, folate, and creatinine did not attenuate the effects.CONCLUSIONS: Low VitB12 concentrations within the normal range are associated with poorer memory performance, which is an effect that is partially mediated by the reduced microstructural integrity of the hippocampus. Future interventional trials are needed to assess whether supplementation of VitB12 may improve cognition in MCI patients even in the absence of clinically manifested VitB12 deficiency. This trial was registered at clinicaltrials.gov as NCT01219244.

AB - BACKGROUND: Low-normal concentrations of vitamin B-12 (VitB12) may be associated with worse cognition. However, previous evidence has been mixed, and the underlying mechanisms remain unclear.OBJECTIVE: We determined whether serum VitB12 concentrations within the normal range were linked to memory functions and related neuronal structures in patients with mild cognitive impairment (MCI).DESIGN: In a cross-sectional design, we assessed 100 amnestic MCI patients (52 women; age range: 50-80 y) with low- and high-normal VitB12 concentration (median split: 304 pmol/L) for memory functions with the use of the Auditory Verbal Learning Test. MRI was performed at 3 tesla (n= 86) for the estimation of the volume and microstructure of the hippocampus and its subfields as indicated by the mean diffusivity on diffusion-weighted images. With the use of a mediation analysis, we examined whether the relation between VitB12 and memory performance was partially explained by volume or microstructure.RESULTS: MCI patients with low-normal VitB12 showed a significantly poorer learning ability (P= 0.014) and recognition performance (P= 0.008) than did patients with high-normal VitB12. Also, the microstructure integrity of the hippocampus was lower in patients with low-normal VitB12, mainly in the cornu ammonis 4 and dentate gyrus region (P= 0.029), which partially mediated the effect of VitB12 on memory performance (32-48%). Adjustments for age, sex, education, apolipoprotein E e4 status, and total homocysteine, folate, and creatinine did not attenuate the effects.CONCLUSIONS: Low VitB12 concentrations within the normal range are associated with poorer memory performance, which is an effect that is partially mediated by the reduced microstructural integrity of the hippocampus. Future interventional trials are needed to assess whether supplementation of VitB12 may improve cognition in MCI patients even in the absence of clinically manifested VitB12 deficiency. This trial was registered at clinicaltrials.gov as NCT01219244.

KW - Aged

KW - Aged, 80 and over

KW - Apolipoprotein E4/blood

KW - Cognition/drug effects

KW - Cognitive Dysfunction/blood

KW - Creatinine/blood

KW - Cross-Sectional Studies

KW - Female

KW - Folic Acid/blood

KW - Genotyping Techniques

KW - Hippocampus/drug effects

KW - Homocysteine/blood

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Memory/drug effects

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Verbal Learning/drug effects

KW - Vitamin B 12/administration & dosage

KW - Mean diffusivity

KW - Vitamin B-12

KW - MCI

KW - Episodic memory

KW - Hippocampus

UR - http://www.scopus.com/inward/record.url?scp=84962700567&partnerID=8YFLogxK

U2 - 10.3945/ajcn.115.116970

DO - 10.3945/ajcn.115.116970

M3 - Article

C2 - 26912492

VL - 103

SP - 1045

EP - 1054

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

SN - 0002-9165

IS - 4

ER -