Milde vitamine B12 deficiëntie en het cognitief functioneren van ouderen : de effectiviteit van orale supplementen

Cobalamin deficiency is common in older people and has been recognised as a possible cause for several clinical manifestations such as anaemia and cognitive impairment. Markers for cobalamin deficiency include increased concentrations of plasma total homocysteine (tHcy) and methylmalonic acid (MMA), and decreased concentrations of holotranscobalamin (holoTC). Cross sectional analysis in this thesis confirmed that impaired cognitive performance was associated with relatively unfavourable concentrations of markers for cobalamin status. These results are in line with findings from previous cross-sectional and prospective studies and suggest a role for cobalamin status in cognitive function, in particular because cobalamin deficiency is highly prevalent in old age. According to our recruitment activities it appeared that 26.6% of the older people had mild cobalamin deficiency, which we defined as low to low-normal cobalamin concentrations in combination with increased MMA concentrations. Normalizing mild cobalamin deficiency, defined as a decrease of respectively 80% to 90% of the estimated maximum reduction in plasma MMA concentrations, could be achieved by supplementing daily oral doses of 647 mg to 1032 mg crystalline cobalamin. The main purpose of our research was to investigate whether daily supplementation with such a high dose of oral cobalamin alone or in combination with folic acid has beneficial effects on cognitive function in people aged 70 years or older with mild cobalamin deficiency. We did this in a double-blind, placebo-controlled trial with a relatively large number of carefully selected participants, and an extensive assessment of cognitive function. In total, 195 individuals were randomized to receive either 1,000 μg cobalamin, or 1,000 μg cobalamin + 400 μg folic acid, or placebo for 24 weeks. Markers for cobalamin status and cognitive function were assessed before and after 24 weeks of treatment. Assessment of cognitive function included the domains of attention, construction, sensomotor speed, memory and executive function. Cobalamin status did not change in the placebo group, whereas oral cobalamin supplementation corrected mild cobalamin deficiency. Improvement in one domain (memory function) was observed in all treatment groups, and was greater in the placebo group than in the group who received cobalamin alone ( P = 0.0036). Oral supplementation with cobalamin alone or in combination with folic acid for 24 weeks was not associated with improvements in other cognitive functions. Blood collection after cessation of oral cobalamin supplementation showed that adequate cobalamin status may maintain for a period of up to 5 months after cessation. Despite the null finding of this trial, recent studies provide clues for future research in improving cognitive function