Patterns of cognitive function in middle-aged and elderly Chinese adults—findings from the EMCOA study

An, Yu; Feng, Liang; Zhang, Xiaona; Wang, Ying; Wang, Yushan; Tao, Lingwei; Lu, Yanhui; Qin, Zike; Xiao, Rong

doi:10.1186/s13195-018-0421-8

Cited by 18 publications

(19 citation statements)

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“…Participants between the ages of 50 and 70 years were selected from a large-scale community-based study entitled the Effects and Mechanism investigation of Cholesterol and Oxysterol on Alzheimer’s disease (EMCOA) study, an ongoing multicenter epidemiological survey funded by the State Key Program of National Natural Science Foundation of China [20]. This study was registered at the Chinese Clinical Trial Registry as ChiCTR-OOC-17011882.…”

Section: Methodsmentioning

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: Methodsmentioning

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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“…A similar conclusion has been arrived by Li and Singh 20 : elderly women displayed faster rate of cognitive decline and more severe cognitive deterioration than elderly men. Additionally, closely related with our study population, An et al 21 inspected the cognitive patterns among the middle-aged and elder Chinese people, specifically considering sex differentiation. They reported that females tend to have verbal memory advantages over their male counterparts independent of age.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, males tend to have more intact cognition in general, with better functions in attention, execution, and processing speed. The disparities in cognition exhibited between the two sex groups have not been fully disclosed, but are considered to be the aftermath of differences in years of educations among that generation of the elderly Chinese population 19,21 .…”

Section: Discussionmentioning

confidence: 99%

Genetic and non-genetic factors associated with the phenotype of exceptional longevity & normal cognition

Han

Chen

Yao

et al. 2020

Sci Rep

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In this study, we split 2156 individuals from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) data into two groups, establishing a phenotype of exceptional longevity & normal cognition versus cognitive impairment. We conducted a genome-wide association study (GWAS) to identify significant genetic variants and biological pathways that are associated with cognitive impairment and used these results to construct polygenic risk scores. We elucidated the important and robust factors, both genetic and non-genetic, in predicting the phenotype, using several machine learning models. The GWAS identified 28 significant SNPs at p-value $$< 3 \times 10^{-5}$$ < 3 × 10 - 5 significance level and we pinpointed four genes, ESR1, PHB, RYR3, GRIK2, that are associated with the phenotype though immunological systems, brain function, metabolic pathways, inflammation and diet in the CLHLS cohort. Using both genetic and non-genetic factors, four machine learning models have close prediction results for the phenotype measured in Area Under the Curve: random forest (0.782), XGBoost (0.781), support vector machine with linear kernel (0.780), and $$\ell _2$$ ℓ 2 penalized logistic regression (0.780). The top four important and congruent features in predicting the phenotype identified by these four models are: polygenic risk score, sex, age, and education.

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“…A two-stage case-control study design was performed for metabolomic analyses: an initial discovery batch (MCI = 75; Control = 70) to identify free oxysterol pro les for MCI diagnosis, which were further validated in the validation batch (MCI = 178; Control = 178). Both MCI cases and controls were from the same source population of the EMCOA study, a prospective, multicenter, observational cohort study of cognitive health in middle-aged and elderly Chinese aged 50-70 years [23]. Demographical information, medical history of chronic diseases, a broad range of neuropsychological tests and dietary surveys of all participants were collected.…”

Section: Study Design and Populationmentioning

confidence: 99%

Altered Circulating Free Oxysterols in Mild Cognitive Impairment: Relationship to Diet, Lipids and Genetics

An¹,

Yu²,

Zhang³

et al. 2020

Preprint

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BackgroundOxysterols, products of cholesterol oxidation, seem dysregulated in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). However, little is known about serum free oxysterol (biologically active form) profiles for MCI.MethodsSerum free oxysterol profiles were measured by ultra-performance liquid chromatography-mass spectrometry in discovery (n = 145) and validation batch (n = 356), both of which were constituted with cognitively normal individuals and MCI patients. We assessed associations of oxysterols with demographics, cognition, diet, lipids and genetics.Results27-Hydroxycholesterol and 7α-hydroxy-3-oxo-4-cholestenoic acid could distinguish MCI from control with good performance in both discovery batch (AUC = 0.80) and validation batch (AUC = 0.71). MCI status could affect correlation patterns among oxysterols, cognition and lipids. Genetic variants in APOE, CYP27A1, CYP46A1 showed inverse associations with cognition and lipids/oxysterol levels while CYP7A1 showed consistent associations.ConclusionsWe identify for the first time an altered free oxysterol profile and report associations with genetic variants in MCI using two-step case-control studies.Trial registration: EMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610

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Patterns of cognitive function in middle-aged and elderly Chinese adults—findings from the EMCOA study

Cited by 18 publications

References 56 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

Genetic and non-genetic factors associated with the phenotype of exceptional longevity & normal cognition

Altered Circulating Free Oxysterols in Mild Cognitive Impairment: Relationship to Diet, Lipids and Genetics

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