The Contribution of Genetic Factors to Cognitive Impairment and Dementia: Apolipoprotein E Gene, Gene Interactions, and Polygenic Risk

Fan, Jialing; Wan, Tao; Li, Xin; Li, He; Zhang, Junying; Wei, Dongfeng; Chen, Yaojing; Zhang, Zhanjun

doi:10.3390/ijms20051177

Cited by 48 publications

(29 citation statements)

References 197 publications

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“…The candidate gene most strongly and consistently associated with a higher risk of developing late‐onset dementia is the apolipoprotein E ( APOE ) gene, which codes for a protein involved in metabolism of fat and cholesterol 24 . Genome‐wide association studies (GWAS) have also identified other genetic variants that may have a role in the risk of dementia such as CLU , CR1 , PICALM , BIN1 , ABCA7 , MS4A , CD33 , EPHA1 , and CD2AP , which are thought to be involved in the regulation of inflammation and immunity, intermediate metabolism, or cell trafficking 25,26 …”

Section: Introductionmentioning

confidence: 99%

How can population‐based studies best be utilized to reduce the global impact of dementia? Recommendations for researchers, funders, and policymakers

Stephan

Siervo

Brayne

2020

Alzheimer's & Dementia

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In the last two decades, there has been in-depth investigation into understanding the pathogenesis, epidemiological profiling, and clinical characterization of dementia. However, these investigations have not led to successful interventions to prevent, delay, or reverse the pathological processes underlying dementia. Recent findings of a decrease in dementia risk in high-income countries such as the UK, USA and the Netherlands highlight that dementia, at least in some cases, is preventable. This article includes a synthesis of current knowledge on dementia epidemiology, biological underpinnings, risk factors, and current prevention programs, with the aim to set the path for research, funding, and policy initiatives to address the global public health challenge of how to prevent dementia or reduce risk within the framework of population-based studies. We advocate for development of novel approaches for intelligent data synthesis that go well beyond single approaches to enable powerful risk stratification analyses. An integrated approach is needed where researchers, funders, policymakers, and stakeholders contribute to and work together to formulate effective strategies for the global monitoring and development of population-based risk reduction, treatment, and prevention programs for dementia.

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Section: Introductionmentioning

confidence: 99%

How can population‐based studies best be utilized to reduce the global impact of dementia? Recommendations for researchers, funders, and policymakers

Stephan

Siervo

Brayne

2020

Alzheimer's & Dementia

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“…These results indicated that the cognitive impairment in mice was speci cally caused by abnormal peripheral blood lipids but not by the expression of APOE in the brain. In AD, accelerated cognitive decline and abnormal internal environment, structure, and function of the brain were also found in APOE ε4 carriers [83]. Leon et al compiled "The Role of APOE in Cerebrovascular…”

Section: Discussionmentioning

confidence: 99%

Association of Lipoprotein and Thyroid Hormones With Cognitive Dysfunction in Patients With Systemic Lupus Erythematosus

Kong

Zhou

et al. 2020

Preprint

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Background: Neuropsychiatric systemic lupus erythematosus (NPSLE) occurs up to 75% of adult SLE patients, and is one of the major causes of death in SLE patients. Cognitive dysfunction is a typical clinical feature of NPSLE, which seriously affects the quality of life of patients. Dyslipidemia and thyroid disease, which were prevalent in SLE patients, both related to the neuropsychiatric disturbances, including significant psychiatric and cognitive disturbance. This study aimed to investigate whether cognitive dysfunction in patients with systemic lupus erythematosus (SLE) was related to the expression of serum thyroid hormone and lipoproteins.Methods: A total of 121 patients with SLE and 65 healthy controls (HCs) at Nanjing Drum Tower Hospital completed a cognitive function test, then 81 SLE patients were divided into high cognition (n=33) group and low cognition group (n=48). The differences in clinical and laboratory tests and the correlations between IgG, IgM, albumin, T3, and T4 levels and cognitive function were analyzed. The enzyme-linked immunosorbent assay was used to determine the serum levels of 4 lipoproteins (APOE, APOA1, IGF-1, and IGFBP7) in 81 patients.Results: Patients with SLE were less educated with abnormal cognitive function compared with HCs. The levels of albumin, T3 (P < 0.05), and T4 decreased in low-cognition patients, while D-dimer, anti-dsDNA antibody, and IgM levels increased. The serum IgG and IgM levels showed a significant negative correlation with partial cognitive function. The serum T3 and T4 levels positively correlated with cognition. The expression of APOE, APOA1, IGF-1, and IGFBP7 showed no difference between the high- and low-cognition groups. However, the serum APOE level negatively correlated with Line Orientation, APOA1 positively correlated with Coding, and IGFBP7 negatively correlated with Graphic copy (P < 0.05), and IGF-1 had no correlation with any cognitive functions.Conclusions: Thyroid hormones (T3 and T4) and lipoproteins (APOE, APOA1, and IGFBP7) were associated with cognitive dysfunction in SLE. Whether T3 and T4 can be used in clinical practice as the biomarkers of cognitive dysfunction in SLE needs further exploration.

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“…Declines of certain cognitive abilities are common complications of aging and identifying risk factors for cognitive decline is essential to search for therapeutic interventions. Known risk factors for cognitive decline include older age, lower education, and genes such as apolipoprotein E ( APOE ) that plays an important role in the risk for Alzheimer’s disease ( Fan et al, 2019 ). APOE is involved in the transport of cholesterol and other lipids between cellular structures ( Mahley, 1988 ).…”

Section: Introductionmentioning

confidence: 99%

Studying the Interplay Between Apolipoprotein E and Education on Cognitive Decline in Centenarians Using Bayesian Beta Regression

et al. 2021

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Apolipoprotein E (APOE) is an important risk factor for cognitive decline and Alzheimer’s disease in aging individuals. Among the 3 known alleles of this gene: e2, e3, and e4, the e4 allele is associated with faster cognitive decline and increased risk for Alzheimer’s and dementia, while the e2 allele has a positive effect on longevity, and possibly on preservation of cognitive function. Education also has an important effect on cognition and longevity but the interplay between APOE and education is not well-characterized. Previous studies of the effect of APOE on cognitive decline often used linear regression with the normality assumption, which may not be appropriate for analyzing bounded and skewed neuropsychological test scores. In this paper, we applied Bayesian beta regression to assess the effect of APOE alleles on cognitive decline in a cohort of centenarians with longitudinal assessment of their cognitive function. The analysis confirmed the negative association between older age and cognition and the beneficial effect of education that persists even at the extreme of human lifespan in carriers of the e3 allele. In addition, the analysis showed an association between APOE and cognition that is modified by education. Surprisingly, an antagonistic interaction existed between higher education and APOE alleles, suggesting that education may reduce the positive effect of APOE e2 and increase the negative effect of APOE e4 at extreme old age.

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The Contribution of Genetic Factors to Cognitive Impairment and Dementia: Apolipoprotein E Gene, Gene Interactions, and Polygenic Risk

Cited by 48 publications

References 197 publications

How can population‐based studies best be utilized to reduce the global impact of dementia? Recommendations for researchers, funders, and policymakers

How can population‐based studies best be utilized to reduce the global impact of dementia? Recommendations for researchers, funders, and policymakers

Association of Lipoprotein and Thyroid Hormones With Cognitive Dysfunction in Patients With Systemic Lupus Erythematosus

Studying the Interplay Between Apolipoprotein E and Education on Cognitive Decline in Centenarians Using Bayesian Beta Regression

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