In cross-sectional studies, low levels of folate and vitamin B12 have been associated with poor cognition and dementia. Results are quite controversial and a debate continues in the literature. Still not completely understood are the differential roles of folate and vitamin B12 in memory acquisition and cognitive development. More intriguing and not fully understood is the rule that treating a vitamin B12-deficient patient with folate may exacerbate the neurological consequences of either deficiency. Starting from these quite confusing perspectives, the aim of this study was to define a possible role of vitamin B12 and folate in cognitive disruption. Data were collected among a cohort of people, admitted to the Neurology Clinic of the University of Trieste, in a period between November 1,2000, and November 1, 2002. We examine potential risk factors, concomitant drug-therapies, and cognitive global performance and correlate these parameters with folate and vitamin B 12 serum levels.We discuss the results with an overview of the literature.