Five cross-sectional observational studies were found that matched the criteria of elderly community-dwelling respondents without dementia whose vitamin B12 and MMA levels were examined in relation to their cognition.2,16,23–25 Most studies used a combination of levels of MMA and B12 to define deficiency, and this prevalence ranged from 25% to 43%. All studies showed an association between higher levels of MMA and cognitive impairment; however, in one study, this was part of low B12 definition rather than explicit,25 and in another, the relationship was lost in multivariate analysis.16 Hin et al.24 define cognitive impairment as scoring less than 22 out of 30 on the Mini-Mental State Examination (MMSE).26 Using multiple regression analysis to control for the effects of age, sex, and smoking, they found almost four times the odds of being in the impaired category with an MMA level in the highest versus the lowest quartile (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.7–8.0). The significance of this relationship may be somewhat attenuated because serum creatinine was not taken into account, but significant relationships were also found between impairment and lower levels of holoTC and B12 (OR, 3.0 and 2.2, respectively). Morris et al.25 modeled cognitive impairment as scoring less than 34 on the Digit Symbol Coding test controlling for age, sex, race, education, and creatinine (among others); they found that low B12 and high MMA were associated with impairment (OR, 1.7; 95% CI, 1.01–2.9), but the primary importance of their study lay in the uncovering of the relationships among B12, folate, and cognition, with high levels of folate being protective with normal B12 (OR, 0.4; 95% CI, 0.2–0.9) but conferring five times the level of risk with low B12 (OR, 5.0; 95% CI, 2.7–9.5). Evidence also exists for the influence of high MMA levels on specific cognitive domains. Using regression modeling to allow for confounders, MMA has been associated with poor results on tests of matrix reasoning23 and with problems in tests of language expression, language comprehension, and praxis2; for example, there is a decrease of 3 points (95% CI, 1–5 points) on the language expression component of the cognitive part of the Cambridge Examination for Mental Disorders of the Elderly27 for each additional unit of MMA.2 Although clearly indicative of risk, the evidence above needs to be examined in longitudinal studies to avoid the possibility of reverse causation.