scholarly journals APOE ε4 and the risk for Alzheimer disease and cognitive decline in African Americans and Yoruba

2014 ◽  
Vol 26 (6) ◽  
pp. 977-985 ◽  
Author(s):  
Hugh C. Hendrie ◽  
Jill Murrell ◽  
Olusegun Baiyewu ◽  
Kathleen A. Lane ◽  
Christianna Purnell ◽  
...  
Keyword(s):  
African Americans ◽  
Cognitive Decline ◽  
Proportional Hazards ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Community Dwelling ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
E4 Allele

ABSTRACTBackground:There is little information on the association of the APOEe4 allele and AD risk in African populations. In previous analyses from the Indianapolis-Ibadan dementia project, we have reported that APOE ε4 increased the risk for Alzheimer's disease (AD) in African Americans but not in Yoruba. This study represents a replication of this earlier work using enriched cohorts and extending the analysis to include cognitive decline.Methods:In this longitudinal study of two community dwelling cohorts of elderly Yoruba and African Americans, APOE genotyping was conducted from blood samples taken on or before 2001 (1,871 African Americans & 2,200 Yoruba). Mean follow up time was 8.5 years for African Americans and 8.8 years for Yoruba. The effects of heterozygosity or homozygosity of ε4 and of the possession of e4 on time to incident AD and on cognitive decline were determined using Cox's proportional hazards regression and mixed effects models.Results:After adjusting for covariates, one or two copies of the APOE ε4 allele were significant risk factors for incident AD (p < 0.0001) and cognitive decline in the African-American population (p < 0001). In the Yoruba, only homozygosity for APOE ε4 was a significant risk factor for AD (p = 0.0002) but not for cognitive decline (p = 0.2346), however, possession of an e4 allele was significant for both incident AD (p = 0.0489) and cognitive decline (p = 0.0425).Conclusions:In this large longitudinal comparative study, APOE ε4 had a significant, but weaker, effect on incident AD and on cognitive decline in Yoruba than in African Americans. The reasons for these differences remain unclear.

scholarly journals Parity and the risk of incident dementia: a COSMIC study

2020 ◽  
Vol 29 ◽  
Author(s):  
J. B. Bae ◽  
D. M. Lipnicki ◽  
J. W. Han ◽  
P. S. Sachdev ◽  
T. H. Kim ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Community Dwelling ◽  
Alzheimer Dementia ◽  
Grand Multiparity ◽  
Incident Dementia

Abstract Aims To investigate the association between parity and the risk of incident dementia in women. Methods We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)). Results Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity. Conclusions Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.

Emotional Loneliness Is Associated With a Risk of Dementia in a General Japanese Older Population: The Hisayama Study

2020 ◽  
Author(s):  
Mao Shibata ◽  
Tomoyuki Ohara ◽  
Masako Hosoi ◽  
Jun Hata ◽  
Daigo Yoshida ◽  
...  
Keyword(s):  
Social Isolation ◽  
Proportional Hazards ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Cox Proportional Hazards ◽  
Community Dwelling ◽  
Physical Factors ◽  
Older Population ◽  
Cox Proportional Hazards Models ◽  
Emotional Loneliness

Abstract Objectives To investigate the association of loneliness and its component subscales with the risk of dementia in a general Japanese older population. Method A total of 1,141 community-dwelling Japanese residents aged ≥65 years without dementia were prospectively followed up for a median 5.0 years. We evaluated any loneliness and its component subscales—namely, social and emotional loneliness—by using the 6-item de Jong Gierveld Loneliness Scale. Cox proportional hazards models were used to estimate hazard ratios (HRs) of each loneliness type on the risk of dementia controlling for demographic factors, lifestyle factors, physical factors, social isolation factors, and depression. Results During the follow-up, 114 participants developed dementia. The age- and sex-adjusted incidence rate of dementia was significantly greater in participants with any loneliness and emotional loneliness than those without. The multivariable-adjusted HRs (95% confidence intervals) of participants with any loneliness and emotional loneliness on incident dementia were 1.61 (1.08–2.40) and 1.65 (1.07–2.54), respectively, as compared to those without. However, there was no significant association between social loneliness and dementia risk. In subgroup analyses of social isolation factors, excess risks of dementia associated with emotional loneliness were observed in participants who had a partner, lived with someone, or rarely communicated with relatives or friends, but such association was not significant in participants who had no partner, lived alone, or frequently communicated with friends or relatives. Discussion The present study suggested that loneliness, especially emotional loneliness, was a significant risk factor for the development of dementia in the general older population in Japan.

Long-term hematologic toxicity of 177Lu-octreotate-capecitabine-temozolomide therapy of GEPNET

2021 ◽  
Author(s):  
Murali Kesavan ◽  
Piyush Grover ◽  
Wei-Sen Lam ◽  
Phillip G Claringbold ◽  
J. Harvey Turner
Keyword(s):  
Cumulative Incidence ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Baseline Risk ◽  
Hematologic Toxicity ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Prospective Phase ◽  
Grade 3

Thirty-seven patients with advanced gastroenteropancreatic neuroendocrine tumors (GEPNETs) were treated on a prospective phase II single-center study with 4 cycles of 7.8 GBq 177Lu-octreotate combined with capecitabine and temozolomide chemotherapy (CAPTEM). Each 8-week cycle combined radiopeptide therapy with 14 days of capecitabine (1500 mg/m2) and 5 days of temozolomide (200 mg/m2). The incidence of grade ≥3 hematologic toxicity was analysed. We found that at a median follow-up of 7-years (range 1-10), 6 (16%) patients developed persistent hematologic toxicity (PHT, defined as sustained grade ≥3 hematologic toxicity beyond 36-months follow up) and 3 (8%) developed MDS/AL with a median time-to-event of 46 and 34-months respectively. Estimated cumulative incidence of MDS/AL was 11% (95% CI: 3.45 to 24.01). Development of PHT was the only significant risk factor for secondary (RR, 16; 95% CI: 2.53 to 99.55; p<0.001). The median PFS was 48 months (95% CI: 40.80-55.20) and median OS was 86 months (95% CI: 56.90-115.13). 21 deaths were recorded, including 13 (62%) due to progressive disease and all 3 (14%) patients with MDS/AL. We conclude that 177Lu-octreotate CAPTEM therapy for GEPNETs is associated with a risk of long-term hematologic toxicity. The rising cumulative incidence of MDS/AL >10% mandates for the long-term monitoring of treated patients. However, time to onset is unpredictable and incidence does not correlate with conventional baseline risk factors. Novel methods are required for stratification of prospective patients based on genetic risk.

scholarly journals Fuchs’ Heterochromic Iridocyclitis in an Italian Tertiary Referral Centre: Epidemiology, Clinical Features, and Prognosis

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Massimo Accorinti ◽  
Giovanni Spinucci ◽  
Maria Pia Pirraglia ◽  
Simone Bruschi ◽  
Francesca Romana Pesci ◽  
...  
Keyword(s):  
Significant Risk ◽  
Significant Risk Factor ◽  
Clinical Findings ◽  
Tertiary Referral Centre ◽  
Blurred Vision ◽  
Visual Prognosis ◽  
Presenting Symptoms ◽  
Significant Incidence ◽  
Keratic Precipitates

Purpose. To study epidemiology, clinical findings and visual prognosis of patients with Fuchs’ Heterochromic Iridocyclitis (FHI).Methods. A retrospective analysis was performed on 158 patients with FHI. Thirty-five patients were observed only once; the remaining 123 had a mean follow-up of 30.7 months (50 of them had a mean follow-up of 63.5 months) and in those we assessed complications, medical and surgical treatment, and long-term visual prognosis.Results. Average age at uveitis diagnosis was 27.2 years and 18.3% of patients were children. Blurred vision (54.5%) and floaters (40.5%) were the most frequent presenting symptoms. Small to medium-sized keratic precipitates (95.6%), iris atrophy (86.8%), and vitreous opacities (91.2%) were the most common signs; the prevalence of cataract and IOP increase was 63.5% and 20.1%, respectively, and their incidence was 0.1 and 0.06 eye/year. Significant risk factor for visual loss was IOP increase at presentation (p=0.02). At final examination 98% of the eye had a visual acuity ≥ 0.6, and topical (p<0.001) and systemic (p<0.001) corticosteroids therapy were used less frequently than before referral.Conclusions. FHI has a good visual prognosis, despite the significant incidence of cataract and glaucoma. A correct and prompt diagnosis might avoid unnecessary therapies and provide excellent visual outcomes.

scholarly journals Circulating metabolomics profiling reveals novel pathways associated with cognitive decline in patients with hypertension

2020 ◽  
Vol 13 ◽  
pp. 175628642094797
Author(s):  
Yuli Huang ◽  
Haoxiao Zheng ◽  
Kuan Tan ◽  
Xiangdong Sun ◽  
Jinshao Ye ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Underlying Mechanism ◽  
Hypertensive Patients ◽  
Benzoate Degradation ◽  
Phenylpropanoid Biosynthesis ◽  
Altered Blood ◽  
State Examination ◽  
Blood Microbiota

Background: Hypertension is a significant risk factor for cardiovascular disease, and it is associated with dementia, including Alzheimer’s disease (AD). Although it may be correlated with AD in terms of symptoms, the link between hypertension and AD pathological biomarkers, and the potential underlying mechanism of hypertension with cognitive decline, are still not well understood. Methods: The Mini-Mental State Examination (MMSE) scores were used to evaluate cognitive function. Enzyme-linked immunosorbent assays were used to examine plasma amyloid-beta (Aβ)40, Aβ42, and tau concentration in hypertensive patients. Metabolomics and metagenomics were performed to identify the significantly changed circulating metabolites and microbiota between healthy individuals and hypertensive patients. Pearson’s correlation was used to examine the association between cognitive indicators and differential metabolites. Results: We found significantly decreased MMSE scores, elevated plasma Aβ40, and decreased Aβ42/Aβ40 ratio in hypertensive patients, which are critically associated with AD pathology. Based on metabolomics, we found that significantly altered metabolites in the plasma of hypertensive patients were enriched in the benzoate degradation and phenylpropanoid biosynthesis pathways, and they were also correlated with changes in MMSE scores and Aβ42/Aβ40 ratio. In addition, metabolomics signaling pathway analysis suggested that microbial metabolism was altered in hypertensive patients. We also identified altered blood microbiota in hypertensive patients compared with the controls. Conclusions: Our study provides a novel metabolic and microbial mechanism, which may underlie the cognitive impairment in hypertensive patients.

Physiological Exophoria Did Not Increase The Incidence of Myopia in Rural School Children in Taiwan

2021 ◽  
Author(s):  
Jui-Hung Hsu ◽  
Li-Ju Lai ◽  
Tao-Hsin Tung ◽  
Wei-Hsiu Hsu
Keyword(s):  
Elementary School ◽  
Logistic Regression ◽  
Elementary School Students ◽  
Multinomial Logistic Regression ◽  
Significant Risk ◽  
Epidemiological Data ◽  
Significant Risk Factor ◽  
Categorical Variables ◽  
School Students

Abstract Purpose:This study evaluated the incidence rate and risk factors for developing myopia in elementary school students in Chiayi, Taiwan.Methods:This prospective cohort study comprised 1816 students without myopia (grades 1 to 5 in Chiayi County). The students underwent a noncycloplegic ocular alignment examinations using an autorefractometer and completed a questionnaires at baseline and at a 1-year follow-up. A univariate logistic regression was used to assess the effects of the categorical variables on new cases of myopia. A multinomial logistic regression was then conducted. A chi-squared test was used to compare new cases of myopia in terms of ocular alignment. A Cox hazard ratio model was then used to validate factors associated with changes in ocular alignment. A P value of <.05 was considered significant.Results: In 370 participants with new cases of myopia out of 1816 participants, a spherical error of −1.51 ± 0.6 diopters was noted at follow-up. The baseline ocular alignment was not a significant risk factor for developing myopia (exophoria vs orthophoria: OR 1.26, 95% CI 0.97-1.62; other vs. orthophoria: OR 1.15, 95% CI 0.73-1.82). However, new cases of myopia (HR 1.36, 95% CI 1.14-1.61), and baseline ocular alignment (exophoria vs orthophoria: HR 3.76, 95% CI 3.20-4.42; other vs orthophoria: HR 3.02, 95% CI 2.05-4.45) were associated with exophoria at follow-up.Conclusions: This study provided epidemiological data on the incidence of myopia in elementary school students in Chiayi, Taiwan. It also demonstrated that physiological exophoria does not predispose patients to developing myopia.

Abstract P322: Myocardial Contraction Fraction is an Independent Predictor of Incident Adverse Cardiovascular Events; The Framingham Heart Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Michael L Chuang ◽  
Philimon Gona ◽  
Connie W Tsao ◽  
Carol J Salton ◽  
Warren J Manning ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Stroke Volume ◽  
Proportional Hazards ◽  
Independent Predictor ◽  
Myocardial Contraction ◽  
Cox Proportional Hazards ◽  
Community Dwelling ◽  
Heart Study ◽  
Myocardial Contraction Fraction

Introduction: Myocardial contraction fraction (MCF) is the ratio of left ventricular (LV) stroke volume to myocardial volume, and thus a measure of LV pumping capacity per unit of myocardium. We sought to determine whether MCF measured using current steady-state free precession (SSFP) cardiac magnetic resonance (CMR) sequences was an independent predictor of incident “hard” cardiovascular disease (CVD) events, defined by myocardial infarction (MI), stroke, unstable angina (UA), hospitalized heart failure (HF) or CVD death in a community dwelling cohort initially free of these CVD events. Methods: 1794 members of the Framingham Heart Study Offspring cohort (aged 65±9 years) underwent CMR between 2002-2006 using a 1.5-Tesla system with contiguous multislice SSFP cine imaging to encompass the left ventricle. MCF was determined from the cine images by a single observer blinded to participant characteristics. We tracked incident hard CVD events over median 6.5-year follow up and used Cox proportional hazards models (adjusted for age, sex, body mass index, systolic blood pressure, diabetes, dyslipidemia, smoking, treatment for hypertension) to determine hazard of hard CVD events per increment (0.10) of MCF. Results: MCF was determined in 1776 (99%) Offspring (835 men). Overall, MCF was greater in women (0.92±0.14 vs. 0.78±0.15 for men), p<0.0001. There were 60 incident hard CVD events during follow up. Incident hard events included 26 MI, 2 UA, 13 stroke, 14 hospitalized HF and 5 CVD deaths. Offspring experiencing an incident event had lower MCF (0.78±0.19 vs. 0.86±0.15 for those free of events), p=0.002. On MV-adjusted Cox proportional hazards analyses, a greater MCF was protective against hard CVD events, HR [95% confidence intervals] = 0.76 [0.63 - 0.93] per 0.10 increment of MCF. Conclusion: Over 6.5-year follow-up, greater MCF is protective against major adverse CVD events, even after adjustment for traditional CVD risk factors in a community dwelling cohort of middle-aged and older predominantly European-descended adults. Determination of MCF requires only knowledge of LV stroke volume and myocardial volume, both of which are routinely determined in a standard CMR examination of the left ventricle, and thus imposes no additional scan-time or analysis burden. While MCF may be clinically useful for prediction of risk for incident hard CVD events, its potential value in younger age groups and other ethnicities remains to be determined.

scholarly journals Novel differences in renal gene expression in a diet-induced obesity model

2018 ◽  
Vol 314 (4) ◽  
pp. F517-F530 ◽  
Author(s):  
Victoria L. Halperin Kuhns ◽  
Jennifer L. Pluznick
Keyword(s):  
Renal Cortex ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Differentially Expressed ◽  
Diet Induced Obesity ◽  
Transcriptional Changes ◽  
Stage Renal Disease ◽  
End Stage ◽  
Upregulated Genes

Obesity is a significant risk factor for both chronic kidney disease and end-stage renal disease. To better understand disease development, we sought to identify novel genes differentially expressed early in disease progression. We first confirmed that mice fed a high-fat (HF) diet exhibit early signs of renal injury including hyperfiltration. We then performed RNA-Seq using renal cortex RNA from C57BL6/J male mice fed either HF or control (Ctrl) diet. We identified 1,134 genes differentially expressed in the cortex on HF vs. Ctrl, of which 31 genes were selected for follow-up analysis. This included the 9 most upregulated, the 11 most downregulated, and 11 genes of interest (primarily sensory receptors and G proteins). Quantitative (q)RT-PCR for these 31 genes was performed on additional male renal cortex and medulla samples, and 11 genes (including all 9 upregulated genes) were selected for further study based on qRT-PCR. We then examined expression of these 11 genes in Ctrl and HF male heart and liver samples, which demonstrated that these changes are relatively specific to the renal cortex. These 11 genes were also examined in female renal cortex, where we found that the expression changes seen in males on a HF diet are not replicated in females, even when the females are started on the diet sooner to match weight gain of the males. In sum, these data demonstrate that in a HF-diet model of early disease, novel transcriptional changes occur that are both sex specific and specific to the renal cortex.

scholarly journals Bi-directional association between epilepsy and dementia

Neurology ◽  
2020 ◽  
Vol 95 (24) ◽  
pp. e3241-e3247 ◽  
Author(s):  
Maria Stefanidou ◽  
Alexa S. Beiser ◽  
Jayandra Jung Himali ◽  
Teng J. Peng ◽  
Orrin Devinsky ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Dementia Risk ◽  
Incident Dementia ◽  
Heart Study ◽  
Allele Status ◽  
Ε4 Allele ◽  
Nested Case Control

ObjectiveTo assess the risk of incident epilepsy among participants with prevalent dementia and the risk of incident dementia among participants with prevalent epilepsy in the Framingham Heart Study (FHS).MethodsWe analyzed prospectively collected data in the Original and Offspring FHS cohorts. To determine the risk of developing epilepsy among participants with dementia and the risk of developing dementia among participants with epilepsy, we used separate, nested, case–control designs and matched each case to 3 age-, sex- and FHS cohort–matched controls. We used Cox proportional hazards regression analysis, adjusting for sex and age. In secondary analysis, we investigated the role of education level and APOE ε4 allele status in modifying the association between epilepsy and dementia.ResultsA total of 4,906 participants had information on epilepsy and dementia and dementia follow-up after age 65. Among 660 participants with dementia and 1,980 dementia-free controls, there were 58 incident epilepsy cases during follow-up. Analysis comparing epilepsy risk among dementia cases vs controls yielded a hazard ratio (HR) of 1.82 (95% confidence interval 1.05–3.16, p = 0.034). Among 43 participants with epilepsy and 129 epilepsy-free controls, there were 51 incident dementia cases. Analysis comparing dementia risk among epilepsy cases vs controls yielded a HR of 1.99 (1.11–3.57, p = 0.021). In this group, among participants with any post–high school education, prevalent epilepsy was associated with a nearly 5-fold risk for developing dementia (HR 4.67 [1.82–12.01], p = 0.001) compared to controls of the same educational attainment.ConclusionsThere is a bi-directional association between epilepsy and dementia. with either condition carrying a nearly 2-fold risk of developing the other when compared to controls.

scholarly journals SURVIVAL ADVANTAGE OF APOE2

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S621-S621
Author(s):  
Sudha Seshadri
Keyword(s):  
Lower Risk ◽  
Large Population ◽  
Population Based ◽  
European Ancestry ◽  
Aggregated Data ◽  
Risk Of Death ◽  
Apoe Ε4 ◽  
Increased Risk ◽  
Ε4 Allele

Abstract Apolipoprotein E is a glycoprotein mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has been associated with higher risk of Alzheimer’s disease and of mortality, but the effect of the less prevalent APOE-ε2 on survival remains elusive. We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six large population-based cohorts to determine the association of APOE-ε2, with survival in the general population. During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P=1.1*10-2), whereas APOE-ε4 carriers were at increased risk (HR 1.17,1.12-1.21; P=2.8*10-16). Risk was lowest for homozygous APOE-ε2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-ε4 (HR 1.52,1.37-1.70). Results did not differ by sex. The association was unaltered after adjustment for baseline LDL or cardiovascular disease. Larger, multiethnic collaborations are ongoing.

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