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Vitamin B-12 concentration, memory performance, and hippocampal structure in patients with mild cognitive impairment
Theresa Köbe1, A Veronica Witte2, Ariane Schnelle1
1Department of Neurology, NeuroCure Cluster of Excellence.
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.
Insights
Low vitamin B-12 (VitB12) levels within the normal range are linked to poorer memory in mild cognitive impairment (MCI) patients. This cognitive decline is partly due to reduced hippocampal microstructure integrity.
Area of Science:
- Neurology
- Nutritional Neuroscience
Background:
- Suboptimal vitamin B-12 (VitB12) levels may impact cognition, but evidence is inconsistent.
- Mechanisms linking low-normal VitB12 to cognitive function require clarification.
Purpose of the Study:
- To investigate the association between serum VitB12 concentrations within the normal range and memory functions in mild cognitive impairment (MCI) patients.
- To explore the relationship between VitB12 levels and hippocampal structure in MCI.
Main Methods:
- Cross-sectional study of 100 MCI patients, divided by median split of serum VitB12 (304 pmol/L).
- Memory assessed using the Auditory Verbal Learning Test.
- Hippocampal volume and microstructure (mean diffusivity) evaluated using 3-tesla MRI in 86 patients.
- Mediation analysis examined if hippocampal integrity mediated the VitB12-memory relationship.
Main Results:
- MCI patients with low-normal VitB12 exhibited significantly poorer learning (P=0.014) and recognition (P=0.008) compared to high-normal VitB12 group.
- Lower hippocampal microstructure integrity, particularly in cornu ammonis 4 and dentate gyrus, was observed in the low-normal VitB12 group (P=0.029).
- Hippocampal microstructure partially mediated the effect of VitB12 on memory performance (32-48%), independent of covariates.
Conclusions:
- Low-normal serum VitB12 concentrations are associated with impaired memory performance in MCI.
- Reduced hippocampal microstructural integrity partially explains this association.
- Further interventional studies are warranted to determine if VitB12 supplementation can enhance cognition in MCI patients without overt deficiency.
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