Sleep mediates the association between homocysteine and oxidative status in mild cognitive impairment

Sanchez-Espinosa, Mayely P.; Atienza, Mercedes; Cantero, José L.

doi:10.1038/s41598-017-08292-4

Cited by 17 publications

(17 citation statements)

References 55 publications

(58 reference statements)

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“…Consequently, lower intake of these B vitamins and elevated serum Hcy level are linked to altered DNA methylation patterns, which has been observed in AD patients [18]. As a neurotoxin, an increased level of Hcy has also been shown to affect redox signaling pathways in neurons by generating reactive oxygen species (ROS) and decreasing endogenous antioxidants [19]. It is therefore of interest to see whether DNA methylation patterns in redox-related genes could modulate cognitive impairment conferred by B vitamin deficiency and hyperhomocysteinemia.…”

Section: Introductionmentioning

confidence: 99%

Dietary intakes and biomarker patterns of folate, vitamin B6, and vitamin B12 can be associated with cognitive impairment by hypermethylation of redox-related genes NUDT15 and TXNRD1

Feng

Zhang

et al. 2019

Clin Epigenet

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Background B vitamins in the one-carbon metabolism pathway (folate, vitamin B6, and vitamin B12) have been implicated in DNA methylation, and their deficiency may contribute to cognitive decline through increased homocysteine (Hcy) levels and subsequent oxidative damage. The aim of this study was to investigate whether B vitamin deficiency and increased Hcy could interact with DNA methylation of oxidative-related genes and exacerbate cognitive impairment. Methods Participants were selected from a large cohort study entitled the Effects and Mechanism Investigation of Cholesterol and Oxysterol on Alzheimer’s disease (EMCOA) study. We included 2533 participants who completed a selection of comprehensive cognitive tests and a semiquantitative food frequency questionnaire (FFQ) and were followed for an average of 2.3 years. The longitudinal effects of B vitamin intake on cognitive decline were examined using linear mixed-effect models. Seven mild cognitive impairment (MCI) patients, in the predementia stage of Alzheimer’s disease (AD), and fivev healthy controls were selected for the discovery of genome-wide differentially methylated CpG sites. Candidate oxidative stress-related genes significantly correlated with serum levels of B vitamins were selected for validation in 102 MCI patients and 68 controls. The correlations between DNA methylation levels and serum concentrations of B vitamins and oxidative biomarkers were analyzed with Spearman’s correlation. The interactive effects of DNA methylation and B vitamins on cognitive performance were further evaluated by multiple linear regression. Results In the prospective analysis, inadequate dietary intake of vitamin B12 was significantly associated with accelerated cognitive decline, whereas adequate folate, vitamin B6, and vitamin B12 intakes were significantly associated with better cognitive reserve. In the case-control analysis, the DNA methylation levels of NUDT15 and TXNRD1 were examined, and significantly hypermethylated sites were identified in MCI patients. Significant correlations of hypermethylated sites with serum levels of folate, homocysteine (Hcy), and oxidative biomarkers were observed, and interactive effects of B vitamins and hypermethylated sites were significantly associated with cognitive performance. Conclusion Adequate dietary folate at baseline predicted a better cognitive reserve, while decreased serum levels of B vitamins may contribute to cognitive impairment by affecting methylation levels of specific redox-related genes. Trial registration EMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610 Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

Dietary intakes and biomarker patterns of folate, vitamin B6, and vitamin B12 can be associated with cognitive impairment by hypermethylation of redox-related genes NUDT15 and TXNRD1

Feng

Zhang

et al. 2019

Clin Epigenet

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“…Another study investigated 21 healthy older adults and 21 individuals with mild cognitive impairment and found that shorter sleep duration may contribute to elevated homocysteine levels and oxidative stress. 24 The other animal study found that sleep deprivation may reduce rather than enhance homocysteine levels in rats. 25 However, no related evidence was collected in human studies.…”

Section: Discussionmentioning

confidence: 97%

Short Sleep Duration Is Associated With Increased Serum Homocysteine: Insights From a National Survey

Chen

Winkelman

Mao

et al. 2019

Journal of Clinical Sleep Medicine

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Study Objectives: Both short sleep duration and increased serum homocysteine levels are associated with cardiovascular events. However, research on the relationship between sleep duration and serum homocysteine levels is sparse. The aim of this study is to examine the association between sleep duration and serum homocysteine levels from a national database. Methods: In total, 4,480 eligible participants older than 20 years who had serum homocysteine data and reported sleep duration were enrolled from the US National Health and Nutrition Examination Survey of 2005 to 2006. The association between sleep duration and serum homocysteine levels was analyzed using multivariate regression models for covariate adjustment. Results: Serum homocysteine level was lowest in individuals with a sleep duration of 7 hours and increased in those with both shorter and longer selfreported total sleep time (groups were categorized into ≤ 5 hours, 6 hours, 7 hours, 8 hours, and ≥ 9 hours). After adjustment for covariates, those in the group sleeping ≤ 5 hours had significantly higher serum homocysteine levels than the reference group (sleep duration of 7 hours). In subgroup analyses by sex, body mass index (BMI), and ethnicity, the association between short sleep duration (≤ 5 hours) and higher serum homocysteine levels persisted in women, individuals with obesity (BMI ≥ 30 kg/m 2 ), and non-Hispanic whites. Conclusions: This study highlighted that short sleep duration was associated with higher serum homocysteine levels in women, individuals with obesity (BMI ≥ 30 kg/m 2 ), and non-Hispanic whites; this finding might suggest increased vulnerability to cardiovascular risk or other atherothrombotic events in these groups in the context of short sleep.

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“…Few studies examined the association between TAC and cognitive impairment in older adults. For instance, one study has suggested that lower level of TAC was independently correlated with less grey matter in the middle temporal lobe in patients with mild cognitive impairment 65 . Another study supported this finding, revealing a considerably lower brain metabolic rate in the inferior and temporal lobes of patients with weak cognitive function when compared to a matched healthy group 66 .…”

Section: Discussionmentioning

confidence: 99%

Associations between vitamin E, oxidative stress markers, total homocysteine levels, and physical activity or cognitive capacity in older adults

Alghadir

Gabr

Anwer

et al. 2021

Sci Rep

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This study examined the associations between vitamin E, oxidative stress markers, total homocysteine levels, and physical activity or cognitive capacity in older adults. One hundred and six older adults (62 men, 44 women) within the age range of 56–81 years participated. The Global Physical Activity Questionnaire and the Loewenstein Occupational Therapy Cognitive Assessment were used to assess physical activity and cognitive function, respectively. Vitamin E (e.g., α-tocopherol and γ-tocopherol), oxidative stress markers (e.g., total antioxidant capacity and nitric oxide), and total homocysteine were estimated. There were significant associations between physical activity (high versus moderate versus poor) and all biomarkers (all p = 0.000, and p = 0.010 for γ-tocopherol). While total homocysteine and total antioxidant capacity were significantly associated with cognitive capacity (p = 0.000), vitamin E levels (e.g., α-tocopherol and γ-tocopherol) and nitric oxide (p = 0.354, 0.103 and 0.060, respectively) were not related to cognitive capacity in older adults. This study concludes that physical activity was associated with Vitamin E, oxidative stress markers, total homocysteine, and cognitive capacity in older adults. Although cognitive capacity was associated with total homocysteine and total antioxidant capacity, it was unrelated to vitamin E levels and nitric oxide in older adults.

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Sleep mediates the association between homocysteine and oxidative status in mild cognitive impairment

Cited by 17 publications

References 55 publications

Dietary intakes and biomarker patterns of folate, vitamin B6, and vitamin B12 can be associated with cognitive impairment by hypermethylation of redox-related genes NUDT15 and TXNRD1

Dietary intakes and biomarker patterns of folate, vitamin B6, and vitamin B12 can be associated with cognitive impairment by hypermethylation of redox-related genes NUDT15 and TXNRD1

Short Sleep Duration Is Associated With Increased Serum Homocysteine: Insights From a National Survey

Associations between vitamin E, oxidative stress markers, total homocysteine levels, and physical activity or cognitive capacity in older adults

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