B VITAMINS MAY BE VITAL TO THE BRAIN
Elevated levels of homocysteine may cause brain atrophy and vascular disease and therefore may be related to the development of dementia and possibly Alzheimer's disease, according to two studies in the May 28 Neurology. About 5% to 7% of the population has mildly elevated levels of homocysteine.
"This is exciting information, because homocysteine levels can be reduced by taking the vitamins B6, B12, and folic acid," said James F. Toole, MD, Professor of Neurology at Wake Forest University School of Medicine in Winston-Salem, North Carolina, and author of an accompanying editorial. He is currently leading a study to examine if vitamin supplementation to lower homocysteine levels can reduce the risk of stroke. Taking vitamins to lower homocysteine levels may also reduce the risk of Alzheimer's disease and other dementia, he believes.
BRAIN ATROPHY ASSOCIATION FOUND
The relationship between high homocysteine levels and brain atrophy was examined in 36 healthy community volunteers (mean age, 71.6; range, 59 to 85 years; 18 men and 18 women) with a mean education level of 12 years and no history of cerebrovascular disease. The researchers hypothesized that "the high homocysteine levels, combined with the increased risk for cerebrovascular disease and possibly neurodegeneration, should manifest in the brains of otherwise healthy elderly individuals in the form of brain atrophy and small vessel disease detectable on MRI [magnetic resonance imaging]." Indeed, the study found that elderly people who had greater brain atrophy were twice as likely to have high homocysteine levels as were those with less atrophy, according to lead author Perminder Sachdev, MD, PhD, Professor of Neuropsychiatry, University of New South Wales in Sydney, Australia.
At the time of assessment, subjects were not taking folate, vitamin B12, or vitamin B6; they underwent a battery of neuropsychological tests and MRI. It was determined that mean total homocysteine level was not significantly correlated with folate levels but was correlated with creatinine levels. Also, homocysteine levels did have a significant relationship with anterior and midsection entricle?brain ratios, although not with cortical atrophy.
SIGNIFICANT CORRELATION IN A SMALL SAMPLE
The authors acknowledged that the sample size was small but noted that the significant correlation between homocysteine levels and an index of brain atrophy in a healthy elderly population is intriguing. The fact that ventricular dilatation and not cortical atrophy was best correlated with homocysteine levels suggested that the measure possibly reflected loss of white matter.
Although the researchers wrote that they "cannot conclude that high homocysteine levels caused brain atrophy," they did speculate on possible mechanisms. While the lack of association between homocysteine levels and white matter hyperintensities makes it unlikely that MRI-visible microangiopathy was a mediating factor, the authors "cannot rule out the possibility that MRI-invisible microangiopathy was related to ventricular dilatation seen in [their] subjects." They allowed that it is possible that homocysteine has a neurotoxic effect or, conversely, may promote neuronal apoptosis. "The association of hyperhomocysteinemia with cerebral atrophy is a possible explanation for its proposal as a risk factor for Alzheimer's disease," they concluded.
VASCULAR DISEASE ALSO SEEN
People with hyperhomocysteinemia were also 10 times more likely to have vascular disease, a study from the University of California, Davis, School of Medicine in Sacramento revealed. The finding was based on a study of 43 people with Alzheimer's disease who were recruited during outpatient visits to the university's Alzheimer's Disease Center and 37 healthy controls who were studied for homocysteine level and B vitamin status.
The patients with Alzheimer's disease underwent testing to exclude other causes of dementia as well as brain imaging (CT or MRI) to determine the presence or absence of cerebral infarction. Of the 43 study participants with a diagnosis of possible or probable Alzheimer's disease, 11 had a coexisting vascular disease such as stroke, myocardial infarction, angina, congestive heart failure, coronary artery disease, transient ischemic attack, or evidence of lacunar or cortical brain infarcts. Of the 37 control subjects without a diagnosis of Alzheimer's disease, 15 had evidence of vascular disease.
Mean plasma homocysteine concentration was higher in the subjects with vascular disease?whether in the Alzheimer's disease group or the control group?than in the subjects without vascular disease, it was reported. No significant effect of Alzheimer's disease on plasma homocysteine concentration was observed.
HIGH HOMOCYSTEINE RELATED TO VASCULAR DISEASE?
"The study didn’t find a relationship between high homocysteine levels and Alzheimer's disease per se?as has been reported previously?but rather suggests that in studies that did demonstrate this association, the effect may be mediated by vascular diseases," said lead author Joshua W. Miller, PhD, Assistant Adjunct Professor in the Department of Pathology. The patients with Alzheimer's disease were also found to be 12 times more likely to have low levels of vitamin B6 than the controls.
The primary conclusion to be drawn from the findings, the authors wrote, is that elevated homocysteine in Alzheimer's disease is not the direct cause or result of Alzheimer's disease pathology or its consequences, either physiologic or behavioral. Instead, they believe, it is related to the well-documented association with vascular disease. It remains to be determined if hyperhomocysteinemia contributes to or is associated with more severe dementia or an accelerated rate of cognitive decline in patients with Alzheimer's disease, they said.
The most effective means for lowering plasma homocysteine is B vitamin supplementation (a combination of folate, vitamin B12, and vitamin B6), the researchers maintain. Based on previous findings as well as their own, Dr. Miller's group believes that a therapeutic effect of vitamin B6 supplementation may be postulated for patients with Alzheimer's disease.
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