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Cognitive Performance in

Cognitive Performance in. Vitamin B12 Deficient Vegan Men wit h. 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.

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Cognitive Performance in

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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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