Novel Functional, Health, and Genetic Determinants of Cognitive Terminal Decline: Kuakini Honolulu Heart Program/Honolulu-Asia Aging Study

2021 ◽  
Author(s):  
Jennifer A Margrett ◽  
Thomas Schofield ◽  
Peter Martin ◽  
Leonard W Poon ◽  
Kamal Masaki ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Cognitive Abilities ◽  
Genetic Risk ◽  
Latent Class ◽  
Functional Health ◽  
Japanese American ◽  
Genetic Determinants ◽  
Aging Study ◽  
Ε4 Allele ◽  
Prior Stroke

Abstract To investigate inter-individual differences in cognitive terminal decline and identify determinants including functional, health, and genetic risk and protective factors, data from the Honolulu Heart Program/Honolulu-Asia Aging Study, a prospective cohort study of Japanese American men, were analyzed. The sample was recruited in 1965-68 (ages 45-68 years). Longitudinal performance of cognitive abilities and mortality status were assessed from Exam 4 (1991-1994) through June 2014. Latent class analysis revealed two groups: maintainers retained relatively high levels of cognitive functioning until death and decliners demonstrated significant cognitive waning several years prior to death. Maintainers were more likely to have greater education, diagnosed coronary heart disease, and presence of the apolipoprotein E (APOE) ε2 allele and FOXO3 G allele (SNP rs2802292). Decliners were more likely to be older and have prior stroke, Parkinson’s disease, dementia, and greater depressive symptoms at Exam 4, and the APOE ε4 allele. Findings support terminal decline using distance to death as the basis for modeling change. Significant differences were observed between maintainers and decliners 15 years prior to death, a finding much earlier compared to the majority of previous investigations.

Plasma Fibrinogen and Coronary Heart Disease in Elderly Japanese-American Men

1996 ◽  
Vol 16 (2) ◽  
pp. 262-268 ◽  
Author(s):  
Dan S. Sharp ◽  
Robert D. Abbott ◽  
Cecil M. Burchfiel ◽  
Beatriz L. Rodriguez ◽  
Russell P. Tracy ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Plasma Fibrinogen ◽  
Japanese American ◽  
Elderly Japanese

scholarly journals Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach

2014 ◽  
Vol 23 (3) ◽  
pp. 381-387 ◽  
Author(s):  
Jorie Versmissen ◽  
Daniëlla M Oosterveer ◽  
Mojgan Yazdanpanah ◽  
Abbas Dehghan ◽  
Hilma Hólm ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Familial Hypercholesterolemia ◽  
Genetic Risk ◽  
Risk Variants ◽  
Genetic Risk Variants

scholarly journals ApoE4 attenuates autophagy via FoxO3a repression in the brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hee-Young Sohn ◽  
Seong-Ik Kim ◽  
Jee-Yun Park ◽  
Sung-Hye Park ◽  
Young Ho Koh ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Late Onset ◽  
Multiple Roles ◽  
Lipid Transport ◽  
Phosphorylated Tau ◽  
Phosphorylation Level ◽  
Ε4 Allele ◽  
Human Brains ◽  
The Brain ◽  
Novel Therapeutic

AbstractApolipoprotein E (ApoE) plays multiple roles in lipid transport, neuronal signaling, glucose metabolism, mitochondrial function, and inflammation in the brain. It is also associated with neurodegenerative diseases, and its influence differs depending on the isoform. In particular, the ε4 allele of APOE is the highest genetic risk factor for developing late-onset Alzheimer’s disease (AD). However, the mechanism by which ApoE4 contributes to the pathogenesis of AD remains unclear. We investigated the effect of ApoE4 on autophagy in the human brains of ApoE4 carriers. Compared to non-carriers, the expression of FoxO3a regulating autophagy-related genes was significantly reduced in ApoE4 carriers, and the phosphorylation level of FoxO3a at Ser253 increased in ApoE4 carriers, indicating that FoxO3a is considerably repressed in ApoE4 carriers. As a result, the protein expression of FoxO3a downstream genes, such as Atg12, Beclin-1, BNIP3, and PINK1, was significantly decreased, likely leading to dysfunction of both autophagy and mitophagy in ApoE4 carriers. In addition, phosphorylated tau accumulated more in ApoE4 carriers than in non-carriers. Taken together, our results suggest that ApoE4 might attenuate autophagy via the repression of FoxO3a in AD pathogenesis. The regulation of the ApoE4-FoxO3a axis may provide a novel therapeutic target for the prevention and treatment of AD with the APOE4 allele.

scholarly journals Clusters of the Risk Markers and the Pattern of Premature Coronary Heart Disease: An Application of the Latent Class Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Leila Jahangiry ◽  
Mahdieh Abbasalizad Farhangi ◽  
Mahdi Najafi ◽  
Parvin Sarbakhsh
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Latent Class Analysis ◽  
High Probability ◽  
Latent Class ◽  
Class Analysis ◽  
Risk Markers ◽  
History Of ◽  
Opium Addiction ◽  
The Mean

Background: Coronary heart disease (CHD) is the major cause of mortality in the world with a significant impact on the younger population. The aim of this study was to identify prematurity among patients with coronary artery bypass graft surgery (CABG) based on the clustering of CHD risk factors.Methods: Patients were recruited from an existing cohort of candidates for CABG surgery named Tehran Heart Center Coronary Outcome Measurement (THC-COM). A latent class analysis (LCA) model was formed using 11 potential risk factors as binary variables: cigarette smoking, obesity, diabetes, family history of CHD, alcohol use, opium addiction, hypertension, history of stroke, history of myocardial infarction (MI), peripheral vascular disease (PVD), and hyperlipidemia (HLP). We analyzed our data to figure out how the patients are going to be clustered based on their risk factors.Results: For 566 patients who were studied, the mean age (SD) and BMI of patients were 59.1 (8.9) and 27.3 (4.1), respectively. The LCA model fit with two latent classes was statistically significant (G2 = 824.87, df = 21, p < 0.0001). The mean (SD) age of patients for Class I and Class II was 55.66 (8.55) and 60.87 (8.66), respectively. Class I (premature) was characterized by a high probability of smoking, alcohol consumption, opium addiction, and a history of MI (P < 0.05), and class II by a high probability of obesity, diabetes, and hypertension.Conclusion: Latent class analysis calculated two groups of severe CHD with distinct risk markers. The younger group, which is characterized by smoking, addiction, and the history of MI, can be regarded as representative of premature CHD.

Abstract 16508: Effect of Disclosure of Genetic Risk for Coronary Heart Disease on Information Seeking and Information Sharing in a Randomized Clinical Trial (from the MI-GENES Investigators)

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Sherry-Ann Brown ◽  
Hayan Jouni ◽  
Erin Austin ◽  
Tariq Marroush ◽  
Iftikhar Kullo ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Information Sharing ◽  
Risk Score ◽  
Information Seeking ◽  
Genetic Risk ◽  
Heart Attack ◽  
Internet Use ◽  
Risk Disclosure ◽  
Chd Risk

Background: Whether disclosing genetic risk for coronary heart disease (CHD) to individuals influences information seeking and information sharing is not known. Methods: The myocardial infarction genes (MI-GENES) trial randomized participants aged 45-65 years who were at intermediate risk for CHD based on conventional risk factors and not on statins, to receive their conventional risk score (CRS) or their CRS plus a genetic risk score (GRS) based on 28 susceptibility variants. CHD risk was disclosed by a genetic counselor and then discussed with a physician. Surveys to assess information seeking (including internet use and accessing electronic health records (EHR)) were completed before and three and six months after risk disclosure. Information sharing parameters were assessed after risk disclosure. We assessed whether these behaviors differed by GRS disclosure, or by high (≥1.1) or low (<1.1) GRS. Adjustments were made for age, sex, family history of CHD, baseline CRS and GRS, and education. Results were reported as the mean difference (and standard error) in the score for each survey response between the GRS and CRS participants, with significance determined by regression analysis. Results: GRS participants accessed their EHR to obtain information related to their CHD risk more than CRS participants (0.14 ± 0.06, p=0.03). Overall internet use (0.61 ± 0.23, p=0.01), as well as internet use to seek information about heart disease (0.14 ± 0.06, p=0.02) and how genetic factors affect risk of having a heart attack (0.23 ± 0.07, p=0.002), was significantly higher in the GRS participants. GRS participants shared information about heart attack risk with others (0.35 ± 0.13, p=0.007), particularly family members (0.1 ± 0.04, p=0.02), (V4: 0.10 ± 0.05, p=0.05), and their primary care provider (V4: 0.15 ± 0.07, p=0.03) more than CRS participants. Internet use, EHR access, and information sharing did not differ significantly between the high and low GRS groups. Conclusions: Disclosure of GRS for CHD resulted in greater information seeking (including internet use and EHR access) and information sharing by study participants. Disclosure of genetic risk for CHD may help advance patient engagement in precision medicine.

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