~ Low Folate Ups Cognitive Impairment and Dementia Risk

A study published in the July 2004 issue of the American Journal of Clinical Nutrition (http://www.ajcn.org/) found an association between low levels of the B vitamin folate and an increased risk of mild cognitive impairment, vascular dementia and Alzheimer’s disease. Folate, among other dietary factors, helps prevent the formation of homocysteine, an amino acid whose elevation has been linked with the development of cardiovascular disease. This study adds to a growing body of evidence suggesting that caradiovascular risk factors are involved in dementia, including Alzheimer’s disease.

The researchers measured blood levels of homocysteine, folate and vitamin B12 in 81 subjects with mild cognitive impairment, 92 subjects with dementia and 55 older individuals who were not cognitively impaired. Of the 92 individuals with dementia, 74 were diagnosed with Alzheimer’s disease and 18 were diagnosed with vascular dementia.

It was discovered that participants with mild cognitive impairment and dementia had significantly lower serum folate levels than the control group. Participants whose folate levels were in the lowest third of all subjects had three times the risk of mild cognitive impairment than those whose levels were in the top third. Subjects with dementia also had higher homocysteine levels, while no difference was found for vitamin B12 levels. Elevated homocysteine levels were found to exist in a greater proportion of subjects with increased disease severity, being found in 31 percent of the controls, 42 percent of those mild cognitive impairment, and 56 percent of those with dementia.

The study was the first attempt to analyze vitamin B12, folate and homocysteine concentrations in subjects with clinically defined mild cognitive impairment. The results suggest that low folate levels may be an early risk factor for the condition which in turn is a strong risk factor for the development of dementia or Alzheimer’s disease.

With the publishing of the Women’s Health Initiative findings concerning the increased risk of reduced cognitive function experienced by women taking estrogen replacement therapy, the question arises if the increased need for folate created by taking estrogen could be involved in this risk.


Recent studies show that people with dementia of the Alzheimer's type have elevated levels of homocysteine in their blood. At an international scientific conference held in The Netherlands the week of April 27, 1998, a team of scientists unveiled findings showing a definitive link between elevated homocysteine and Alzheimer's disease. The scientists advocated that people have their blood tested for homocysteine in order to determine how much folic acid should be taken to drop homocysteine levels to the safe range.

While the scientists speculated that Alzheimer's disease could be avoided if people reduced their homocysteine levels, it has not yet been determined whether homocysteine itself contributes to Alzheimer's disease. A more likely explanation is that elevated homocysteine is an indication of the severe disruption in the methylation pathway that occurs in the brains of Alzheimer's patients. It has been reported that people with Alzheimer's disease have virtually no S-adenosylmethionine (SAMe) in their brains. SAMe is required for DNA methylation (maintenance and repair) of brain cells. Thus, while homocysteine itself may not cause Alzheimer's disease, it appears to represent an important measurable biomarker of a methylation deficit that could cause Alzheimer's and a host of other degenerative diseases.

Research reported at Tufts University in 1995 documented the same finding linking elevated homocysteine and Alzheimer's disease and recommended supplementation with folic acid and vitamin B12. It should be noted that dementia can be caused by a deficiency of vitamin B12, folic acid, and other nutrients, so another reason people with dementia of the Alzheimer's type have elevated homocysteine levels could be that they are suffering from a common vitamin deficiency. Numerous studies conducted on the elderly show that deficiencies of folic acid, vitamin B12, and other nutrients are epidemic in elderly people who do not take vitamin supplements. Since both elevated homocysteine and vitamin deficiencies have been linked to dementia, the best approach to preventing and treating dementia (including Alzheimer's dementia) would appear to be testing the blood for elevated homocysteine and taking methylation enhancing nutrients such as folic acid, TMG, and vitamin B12.

Those with a family history of heart disease, stroke, or Alzheimer's disease are at a particular risk for elevated homocysteine. Elevated homocysteine has also been linked to complications in diabetes, lupus, and other chronic diseases. While many people have assumed that because they are taking vitamin supplements, their homocysteine levels will be in a safe range, The Life Extension Foundation has discovered that this might not always be the case.

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