Higher homocysteine associated with thinner cortical gray matter in 803 participants from the Alzheimer's Disease Neuroimaging Initiative

Madsen, Sarah K.; Rajagopalan, Priya; Joshi, Shantanu H.; Toga, Arthur W.; Thompson, Paul M.

doi:10.1016/j.neurobiolaging.2014.01.154

Cited by 56 publications

(39 citation statements)

References 77 publications

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“…We recently reported that older adults with higher homocysteine levels had more pronounced regional brain atrophy (13) and thinner cortical gray matter (14) on MRI. We also found that the C677T variant in MTHFR was associated with smaller regional brain volumes in two independent elderly cohorts with mild cognitive impairment (MCI) (15).…”

Section: Introductionmentioning

confidence: 99%

The C677T Variant in MTHFR Modulates Associations Between Brain Integrity, Mood, and Cognitive Functioning in Old Age

Roussotte

Hou

Narr

et al. 2017

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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Introduction The C677T functional variant in the methylene-tetrahydrofolate reductase (MTHFR) gene leads to reduced enzymatic activity and elevated blood levels of homocysteine. Hyperhomocysteinemia has been linked with higher rates of cardiovascular diseases, cognitive decline, and late-life depression. Methods and Materials Here, 3D magnetic resonance imaging data was analyzed from 738 individuals (age: 75.5 ± 6.8 years; 438 men/300 women) including 173 Alzheimer's patients, 359 subjects with mild cognitive impairment, and 206 healthy older adults, scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Results We found that this variant associates with localized brain atrophy, after controlling for age, sex, and dementia status, in brain regions implicated in both intellectual and emotional functioning, notably the medial orbitofrontal cortices. The medial orbitofrontal cortex is involved in the cognitive modulation of emotional processes, and localized atrophy in this region was previously linked with both cognitive impairment and depressive symptoms. Here, we report that increased plasma homocysteine mediates the association between MTHFR genotype and lower medial orbitofrontal volumes, and that these volumes mediate the association between cognitive decline and depressed mood in this elderly cohort. We additionally show that vitamin B12 deficiency interacts with the C677T variant in the etiology of hyperhomocysteinemia. Conclusion This study sheds light on important relationships between vascular risk factors, age-related cognitive decline, and late-life depression, and represents a significant advance in our understanding of clinically relevant associations relating to MTHFR genotype.

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Section: Introductionmentioning

confidence: 99%

The C677T Variant in MTHFR Modulates Associations Between Brain Integrity, Mood, and Cognitive Functioning in Old Age

Roussotte

Hou

Narr

et al. 2017

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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“…It is directly toxic to neurons and blood vessels and can induce DNA strand breakage, oxidative stress, and apoptosis [11]. The role of HCY as a potential and predictive biomarker in Alzheimer's disease [12], cognitive impairment [13], and autism [14] has been well recognized. Studies in other countries report the same dose-response relationship between homocysteine and vascular disease [15,16].…”

Section: Introductionmentioning

confidence: 99%

Serum Levels of High-sensitivity C-Reactive Protein at Admission Are More Strongly Associated with Poststroke Depression in Acute Ischemic Stroke than Homocysteine Levels

et al. 2015

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Inflammatory processes have fundamental roles in depression. The primary purpose of this study was to assess the serum levels of high-sensitivity C-reactive protein (Hs-CRP) and homocysteine (HCY) at admission to the presence of poststroke depression (PSD). From December 2012 to December 2013, first-ever acute ischemic stroke patients who were admitted to the hospital within the first 24 h after stroke onset were consecutively recruited and followed up for 6 months. Serum levels of Hs-CRP and HCY were tested at admission. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for depression at 6 months after stroke. Ninety-five patients (42.0%) showed depression (major + minor) at 6 months after admission, and in 69 patients (30.5%), this depression was classified as major. In the 69 patients with major depression, our results showed significantly higher Hs-CRP and HCY levels at admission than patients without major depression. After adjusting all other possible covariates, Hs-CRP and HCY still were independent predicators of PSD with adjusted OR of 1.332 (95% CI, 1.230-1.452; P < 0.001) and 1.138 (95% CI, 1.072-1.274; P < 0.001), respectively. The area under the receiver operating characteristic curve values of Hs-CRP and HCY were 0.765 (95% CI, 0.701-0.9825) and 0.684 (95% CI, 0.610-0.757) for PSD, respectively. The prognostic accuracy of combined model (HCY and Hs-CRP) was higher compared to those biomarkers alone and other markers. Elevated serum levels of Hs-CRP and HCY at admission were found to be associated with depression 6 months after stroke, suggesting that these alterations might participate in the pathophysiology of depression symptoms in stroke patients.

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“…Brain neuroimaging revealed an association between elevated tHcy and lower subcortical brain volumes and cortical thickness, volume, and surface area in elderly people [60]. Vitamin B treatment has been shown to slow brain volume shrinkage [61], prevent atrophy of gray matter [62], and slow cognitive decline in people with mild cognitive impairment [63], an effect that was not confirmed by all studies [64].…”

Section: Folate Aging and Populationattributable Risk Of Diseasesmentioning

confidence: 99%

Folate status and health: challenges and opportunities

Obeid¹,

Oexle

Rißmann

et al. 2016

Journal of Perinatal Medicine

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Abstract:Each year approximately 2400 pregnancies develop folic acid-preventable spina bifida and anencephaly in Europe. Currently, 70% of all affected pregnancies are terminated after prenatal diagnosis. The prevalence of neural tube defects (NTDs) has been significantly lowered in more than 70 countries worldwide by applying fortification with folic acid. Periconceptional supplementation of folic acid also reduces the risk of congenital heart diseases, preterm birth, low birth weight, and health problems associated with child mortality and morbidity. All European governments failed to issue folic acid fortification of centrally processed and widely eaten foods in order to prevent NTDs and other unwanted birth outcomes. The estimated average dietary intake of folate in Germany is 200 μg dietary folate equivalents (DFE)/day. More than half of German women of reproductive age do not consume sufficient dietary folate to achieve optimal serum or red blood cell folate concentrations ( > 18 or 1000 nmol/L, respectively) necessary to prevent spina bifida and anencephaly. To date, targeted supplementation is recommended in Europe, but this approach failed to reduce the rate of NTDs during the last 10 years. Public health centers for prenatal care and fortification with folic acid in Europe are urgently needed. Only such an action will sufficiently improve folate status, prevent at least 50% of the NTD cases, reduce child mortality and morbidity, and alleviate other health problems associated with low folate such as anemia.

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Higher homocysteine associated with thinner cortical gray matter in 803 participants from the Alzheimer's Disease Neuroimaging Initiative

Cited by 56 publications

References 77 publications

The C677T Variant in MTHFR Modulates Associations Between Brain Integrity, Mood, and Cognitive Functioning in Old Age

The C677T Variant in MTHFR Modulates Associations Between Brain Integrity, Mood, and Cognitive Functioning in Old Age

Serum Levels of High-sensitivity C-Reactive Protein at Admission Are More Strongly Associated with Poststroke Depression in Acute Ischemic Stroke than Homocysteine Levels

Folate status and health: challenges and opportunities

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