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Cognitive Performance in Vitamin B12 Deficient Vegan Men with Intermediate Hyperhomocysteinaemia

This study investigates cognitive performance in healthy male vegans with low to normal Vitamin B12 levels and hyperhomocysteinaemia. A cross-sectional and double-blind RCT design was used, targeting an age-diverse sample (N=138). Neuropsychological tests were conducted before and after 3 months of B12 supplementation (5mg/day). Results indicated no significant differences in cognitive performance based on Vitamin B12 levels or treatment phase, suggesting that low B12 and intermediate hyperhomocysteinaemia may not be linked to cognitive dysfunction, potentially due to compensatory mechanisms like high folate levels and good cerebrovascular function.

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Cognitive Performance in Vitamin B12 Deficient Vegan Men with Intermediate Hyperhomocysteinaemia

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  1. Cognitive Performance in Vitamin B12 Deficient Vegan Men with Intermediate Hyperhomocysteinaemia Vaughan Bell 1, Zouë Lloyd-Wright 2, Jan Møller 3, Anne-Mette Hvas 3, Ebba Nexø 3, Virginia Ng 2, Steven Williams 2, Tim Key 4, Tom A. B. Sanders 2 1 Cardiff University, 2 Kings College London, 3 Aarhus University Hospital, 4 Oxford University

  2. Aims • Previous studies have typically worked with: • Older adults / demented patients • Inappropriate cognitive tests (e.g. MMSE) • We targeted low / normal B12 vegans • Otherwise healthy, with full age range. • Used cross-sectional / double-blind RCT supplementation design. • Relevant and robust neuropsychological tests. • Comprehensive structural neuroimaging.

  3. Sample Vegan males, N = 138 Three groups No significant differences between groups on age, mean veganism, NART IQ

  4. Homocysteine Baseline total mean = 19.4 μmol/L (22.6) SD = 36.89 SD = 13.38 SD = 2.54 ANOVAp < 0.0005, Pearson r = -.352, p < 0.0005

  5. Design • Phase 1: Baseline assessment • Comparison between B12 groups • Phase 2: Double blind RCT: Four groups • 5mg/day B12 supplementation • Tested again after 3 months • Compared active / placebo

  6. Effect of Supplementation

  7. Cognitive Tests • Tests were chosen to be: • Sensitive to sub-clinical and clinical deficits. • Have known links to functional neuroanatomy. • Well controlled (computer presented) • And for semantic and working memory tasks: • Have varying levels of demand. • Have clear patterns of performance in healthy participants.

  8. Episodic Memory One way ANOVA (B12 Group) Two-way mixed ANOVA (Phase x Treatment) • Free recall • No effect of group (p = 0.94), phase (p = 0.62) • No phase x treatment interaction (p = 0.39) • Single-probe recognition • No effect of group (p = 0.55), phase (p = 0.19) • No phase x treatment interaction (p = 0.22)

  9. Semantic Memory Multi-factorial sentence verification task (Kounios & Holcomb, 1992) ALL BIRDS ARE CROWS NO VEGETABLES ARE HAMMERS • Semantic manipulation: • High / low relatedness • Category / exemplar order • ‘All’ / ‘No’ sentence

  10. Semantic Memory One way ANOVA (B12 Group) Two-way mixed ANOVA (Phase x Treatment) • No main effect of group (p = 0.37) • Main effect for phase (p = 0.004, practice effect) • No phase x treatment interaction (p = 0.90) • All semantic manipulations had expected effect

  11. Working memory n-back task (Braver et al., 1997) • Random letters appear on-screen one by one. • Four conditions: 0, 1, 2 and 3-back • Participants must indicate if the letter on-screen matches the letter n-back. • 33% targets in each condition. • Prefrontal cortex involvement directly related to working memory load.

  12. Working memory Phase 1

  13. Working memory Phase 2

  14. Working memory n-back task (Braver et al., 1997) • 3 way ANOVA: treatment x phase x n-back • Main effect for n-back (p < 0.0005) • No main effect for phase (p = 0.092) • No main effect for treatment (p = 0.586) • No interactions

  15. Neuroimaging 18 males with < 120ng/L for 10+ years, brain / spine scans with 1.5 Telsa structural MRI (T1 / T2 / FLAIR) • 50 yr vegan male with dorsal spinal column demyelination • T2 weighted MRI scan of upper thoracic area. Nakamura and Swanson (2004) Present study

  16. Neuroimaging No evidence of brain / spinal column neuropathology when assessed by a consultant radiologist. No evidence of clinical signs of B12 deficiency (e.g. tingling, fatigue, weakness, confusion)

  17. Very Low B12 Participants • Imaging included 3 participants with very low B12 levels (8, 33 and 38 ng/L) • Cognitive tests showed no obvious deficits

  18. Possible explanation Compensation from excellent cerebrovascular function and high levels of folate UK omnivore male mean No main effect (p = 0.78), no post-hoc differences

  19. Possible explanation • e.g. low folate largely known to be linked to poor cognition in older adults, independent of B12, B6, homocysteine levels (Kado et al., 2005). • Although see Morris et al. (2005).

  20. Conclusions • Low B12 and hyperhomocysteinanemia not necessarily associated with: • Cognitive dysfunction • Neuropathology • Our sample possibly protected by: • high levels of folate • excellent cerebrovascular function

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