Carried out by researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, the study made use of an experimental model to examine the metabolic, cognitive, and microvascular effects of dietary B-vitamin deficiency.
"Metabolic impairments induced by a diet deficient in three B-vitamins -folate, B12 and B6- caused cognitive dysfunction and reductions in brain capillary length and density in our mouse model. The vascular changes occurred in the absence of neurotoxic or degenerative changes," said Aron Troen, PhD, the study's lead author.
He added: "Mice fed a diet deficient in folate and vitamins B12 and B6 demonstrated significant deficits in spatial learning and memory compared with normal mice."
The researchers noticed similar but less pronounced differences between normal mice and a third group of mice that were fed a diet enriched with methionine.
"The B-vitamin-deficient mice also developed plasma homocysteine concentrations that were seven-fold higher than the concentrations observed in mice fed a normal diet," said Troen.
Homocysteine is produced by the breakdown of a dietary protein called methionine. B-vitamins, including folate, vitamin B12, and vitamin B6, are required to convert homocysteine back to methionine, thereby reducing the blood concentration of homocysteine.
Studies have linked elevations in plasma homocysteine with an increased risk for cognitive impairment.
"However, it has not been determined that homocysteine is directly responsible. Based on the findings of our study, we theorize that a deficiency of B-vitamins induces a metabolic disorder that manifests with high homocysteine, as well as cerebral microvascular dysfunction," said Troen.
Irwin Rosenberg, MD, director of the Nutrition and Neurocognition Laboratory at the HNRCA, said: "The elevated levels of homocysteine that were associated with vascular cognitive impairment in the mice in our study are comparable to the levels that are associated in older adults with an increased risk for Alzheimer's disease and cerebrovascular disease, the latter of which manifests with conditions such as stroke and atherosclerosis.
He added: "These findings may indicate that microvascular changes mediate the association between high homocysteine levels and human age-related cognitive decline."