Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun Study

Snowdon, David A.; Tully, Christine L.; Smith, Charles D.; Riley, Kathryn; Markesbery, William R.

doi:10.1093/ajcn/71.4.993

Cited by 244 publications

(146 citation statements)

References 26 publications

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“…Nonhomocysteine mechanisms involving methylation reactions in the brain [42] have also been postulated to explain the association between folate intake and AD development. Of interest, 2 studies have associated atrophy in different areas of the brain to serum folate levels [43] or homocysteine levels [27], but the mechanisms for these results are not known.…”

Section: Discussionmentioning

confidence: 99%

Reduced risk of Alzheimer's disease with high folate intake: The Baltimore Longitudinal Study of Aging

Corrada

Kawas

Hallfrisch

et al. 2005

Alzheimer's & Dementia

135

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Background-Study findings have suggested an association between Alzheimer's disease (AD) risk and several vitamins and have speculated about their use as preventive agents. Here, we examine whether total intake (intake from diet plus supplements) of antioxidant vitamins (E, C, carotenoids) and B vitamins (folate, B 6 , and B 12 ) is associated with a reduced risk of AD.Methods-Participants were 579 nondemented elderly volunteers from the Baltimore Longitudinal Study of Aging who completed dietary diaries and recorded supplement intake for a 7-day period. Cox regression was used to estimate the relative risk (RR) of AD associated with total vitamin intake categorized into levels above or below the Recommended Dietary Allowance (RDA).Results-After a mean follow-up of 9.3 years, AD developed in 57 participants. Higher intake of folate (RR, 0.41; 95% confidence interval [CI], 0.22 to 0.76), vitamin E (RR, 0.56; 95% CI, 0.30 to 1.06), and vitamin B 6 (RR, 0.41; 95% CI, 0.20 to 0.84) were associated individually with a decreased risk of AD after adjusting for age, gender, education, and caloric intake. When these 3 vitamins were analyzed together, only total intake of folate at or above the RDA (RR, 0.45; 95% CI, 0.21 to 0.97) was associated with a significant decreased risk of AD. No association was found between total intake of vitamins C, carotenoids, or vitamin B 12 and risk of AD.Conclusions-These findings suggest that total intake of folate at or above the RDA is associated with a reduced risk of AD. Additional studies are necessary to further investigate whether folate or other(s) unmeasured factor(s) may be responsible for this reduction in risk.

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Section: Discussionmentioning

confidence: 99%

Reduced risk of Alzheimer's disease with high folate intake: The Baltimore Longitudinal Study of Aging

Corrada

Kawas

Hallfrisch

et al. 2005

Alzheimer's & Dementia

135

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“…People with neurodegenerative diseases have higher levels of circulating tHcy and people with Alzheimer's disease (AD) that have higher baseline levels of tHcy show a more rapid progression of the disease over a three year period (Clarke et al, 1998). In addition, serum folate levels are negatively correlated with severity of post-mortem cerebral atrophy in AD patients (Snowdon et al, 2000). These effects have prompted speculation that greater intake of B vitamins may reduce the risk or reverse some of the deleterious symptoms associated with high tHcy and dementia.…”

Section: Introductionmentioning

confidence: 99%

“…Neuroimaging methods that allow for a non-invasive investigation of brain morphology and function provide another means to study the effects of B vitamin intake and tHcy in aged individuals. For example, higher levels of tHcy is related to more advanced atrophy of the medial temporal lobe in people with AD, and the rate of atrophy over a three year period is more rapid in those with higher tHcy levels at the initial assessment (Snowdon et al, 2000). Both hippocampal width (Williams et al, 2002) and volume (Bleich et al, 2003), and anterior lateral ventricle-brain ratios (Sachdev et al, 2002), are inversely related to tHcy levels.…”

Section: Introductionmentioning

confidence: 99%

Greater intake of vitamins B6 and B12 spares gray matter in healthy elderly: A voxel-based morphometry study

et al. 2008

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Previous studies have reported that high concentrations of homocysteine and lower concentrations of vitamin B6, B12, and folate increase the risk for cognitive decline and pathology in aging populations. In this cross-sectional study, high-resolution magnetic resonance imaging (MRI) scans and a 3-day food diary were collected on 32 community-dwelling adults between the ages of 59 and 79. We examined the relation between vitamin B6, B12, and folate intake on cortical volume using an optimized voxel-based morphometry (VBM) method and global gray and white matter volume after correcting for age, sex, body mass index, calorie intake, and education. All participants met or surpassed the recommended daily intake for these vitamins. In the VBM analysis, we found that adults with greater vitamin B6 intake had greater gray matter volume along the medial wall, anterior cingulate cortex, medial parietal cortex, middle temporal gyrus, and superior frontal gyrus, whereas people with greater B12 intake had greater volume in the left and right superior parietal sulcus. These effects were driven by vitamin supplementation and were negated when only examining vitamin intake from diet. Folate had no effect on brain volume. Furthermore, there was no relationship between vitamin B6, B12, or folate intake on global brain volume measures, indicating that VBM methods are more sensitive for detecting localized differences in gray matter volume than global measures. These results are discussed in relation to a growing literature on vitamin intake on agerelated neurocognitive deterioration.

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“…I nadequate dietary levels of the vitamin folate can lead to megaloblastic anemia, birth defects, impaired cognitive development, and increased risk of cardiovascular disease and cancer (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). The March of Dimes has stated that inadequate intake of folate before pregnancy is the most common cause of birth defects, including neural tube defects (NTDs) such as spina bifida and anencephaly.…”

mentioning

confidence: 99%

Enhancement of folates in plants through metabolic engineering

Hossain

Rosenberg

Selhub

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

118

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Humans depend on plants as a major source of dietary folates. Inadequate dietary levels of the vitamin folate can lead to megaloblastic anemia, birth defects, impaired cognitive development, and increased risk of cardiovascular disease and cancer. The biofortification of folate levels in food crops is a target for metabolic engineering. Folates are synthesized de novo from pterins and para-amino benzoic acid, which are subsequently combined to form dihydropteroate, the direct precursor to dihydrofolate. We postulated that GTP cyclohydrolase-1, which catalyzes the first committed step in pterin biosynthesis, was a rate-limiting step in pterin synthesis in plants and, therefore, in folate synthesis. On this basis, we proposed that the expression of an unregulated bacterial GTP cyclohydrolase-1 in plants would increase pterin biosynthesis with a concomitant enhancement of folate levels. The folE gene encoding GTP cyclohydrolase-1 was cloned from Escherichia coli and introduced into Arabidopsis thaliana through plant transformation. The expression of bacterial GTP cyclohydrolase-1 in transgenic Arabidopsis resulted in a 1,250-fold and 2-to 4-fold enhancement of pterins and folates, respectively. These results helped to identify other potential factors regulating folate synthesis, suggesting ways to further enhance folate levels in food crops.

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Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun Study

Cited by 244 publications

References 26 publications

Reduced risk of Alzheimer's disease with high folate intake: The Baltimore Longitudinal Study of Aging

Reduced risk of Alzheimer's disease with high folate intake: The Baltimore Longitudinal Study of Aging

Greater intake of vitamins B6 and B12 spares gray matter in healthy elderly: A voxel-based morphometry study

Enhancement of folates in plants through metabolic engineering

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