Folate, Vitamin B12, and Serum Total Homocysteine Levels in Confirmed Alzheimer Disease

Clarke, Robert; Smith, A.D.; Jobst, K; Refsum, Helga; Sutton, Lisa; Ueland, Per Magne

doi:10.1001/archneur.55.11.1449

Cited by 1,314 publications

(983 citation statements)

References 41 publications

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“…Supporting this notion are studies that show a relation between vascular disease and AD [37][38][39]. Homocysteine, however, has also been shown to be a risk factor in patients with neuropathologically confirmed AD without significant cerebrovascular disease or atherosclerosis [27]. More recent animal studies [40] provide evidence that folic acid deficiency and homocysteine may be directly related to amyloid toxicity by impairing DNA repair in neurons, which results in sensitization to oxidative damage induced by β-amyloid (a protein that is accumulated in excess in AD brains).…”

Section: Discussionmentioning

confidence: 96%

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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

137

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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: 96%

“…This lower intake, however, could have been caused by dietary changes in cases of AD. Most studies reporting the association between AD and B vitamins have looked at plasma or serum levels, not intake, and most have been small case-control studies [25][26][27][28][29]. Only 2 prospective studies have looked at this association [7,8].…”

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

137

View full text Add to dashboard Cite

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“…OPTIMA initiated in 1988, is a prospective, longitudinal clinico‐pathological study of dementia and aging including CSF collection at multiple time points during clinical follow‐up. All clinical and pathological protocols have been described in detail13 and were approved by the local ethics committee and participants provided informed consent prior to enrollment.…”

Section: Methodsmentioning

confidence: 99%

Alpha‐synuclein RT‐QuIC in the CSF of patients with alpha‐synucleinopathies

Fairfoul

McGuire

Pal

et al. 2016

Ann Clin Transl Neurol

441

288

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We have developed a novel real‐time quaking‐induced conversion RT‐QuIC‐based assay to detect alpha‐synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson's disease patients. This assay can detect alpha‐synuclein aggregation in Dementia with Lewy bodies and Parkinson's disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results. These results suggest that RT‐QuiC analysis of cerebrospinal fluid is potentially useful for the early clinical assessment of patients with alpha‐synucleinopathies.

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“…1) (1) . This longitudinal study compared Hcy levels taken during life from seventy-six cases with a histological diagnosis of 'Alzheimer's disease' made at post mortem with 108 controls without cognitive impairment.…”

Section: Dementiamentioning

confidence: 99%

B-vitamins and prevention of dementia

Clarke

2008

Proc. Nutr. Soc.

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Elevated plasma homocysteine (Hcy) concentrations have been implicated with risk of cognitive impairment and dementia, but it is unclear whether low vitamin B 12 or folate status is responsible for cognitive decline. Most studies reporting associations between cognitive function and Hcy or B-vitamins have used a cross-sectional or case-control design and have been unable to exclude the possibility that such associations are a result of the disease rather than being causal. The Hcy hypothesis of dementia has attracted considerable interest, as Hcy can be easily lowered by folic acid and vitamin B 12 , raising the prospect that B-vitamin supplementation could lower the risk of dementia. While some trials assessing effects on cognitive function have used folic acid alone, vitamin B 12 alone or a combination, few trials have included a sufficient number of participants to provide reliable evidence. An individualpatient-data meta-analysis of all randomised trials of the effects on cognitive function and vascular risk of lowering Hcy with B-vitamins will maximise the power to assess the epidemiologically-predicted differences in risk. Among the twelve large randomised Hcy-lowering trials for prevention of vascular disease, data should be available on about 30 000 participants with cognitive function. The principal investigators of such trials have agreed to combine individual-participant data from their trials after their separate publication.Folate: Vitamin B 12 : Homocysteine: Dementia

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Folate, Vitamin B12, and Serum Total Homocysteine Levels in Confirmed Alzheimer Disease

Cited by 1,314 publications

References 41 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

Alpha‐synuclein RT‐QuIC in the CSF of patients with alpha‐synucleinopathies

B-vitamins and prevention of dementia

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