Serum Vitamin B12, and Related MTRR and Cubilin Genotypes, Predict Neural Outcomes across the AD Spectrum.

Epidemiological studies show mixed findings for serum vitamin B12 and both cognitive and regional volume outcomes. No studies to date have comprehensively examined, in non-supplemented individuals, serum B12 level associations with neurodegeneration, hypometabolism, and cognition across the Alzheimer's disease (AD) spectrum. Serum vitamin B12 was assayed from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL). Voxel-wise analyses regressed B12 levels against regional gray matter (GM) volume and glucose metabolism (p<.05, family-wise corrected). For ADNI GM, there were 39 cognitively normal (CN), 73 mild cognitive impairment (MCI), and 31 AD participants. For AIBL GM, there were 311 CN, 59 MCI, and 31 AD participants. Covariates were age, sex, baseline diagnosis, APOE4 status, and Body Mass Index (BMI). In ADNI, higher B12 was negatively associated with GM in the right precuneus and bilateral frontal gyri. When diagnostic groups were examined separately, only participants with MCI or above an established cutoff for CSF total tau showed such associations. In AIBL, higher B12 was associated with more grey matter in the right amygdala and right superior temporal pole, which largely seemed to be driven by CN participants that constituted most of the sample. Our results suggest that B12 may show different patterns of association based on clinical status and, for ADNI, AD CSF biomarkers. Accounting for these factors may clarify the relationship between B12 with neural outcomes in late-life.