Dataset Information

Mortality in Patients With Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.

ABSTRACT:

Background and objectives

To determine the risk of mortality and causes of death in persons with late-onset epilepsy (LOE) compared to those without epilepsy in a community-based sample, adjusting for demographics and comorbid conditions.

Methods

This is an analysis of the prospective Atherosclerosis Risk in Communities study, initiated in 1987-1989 among 15,792 mostly Black and White men and women in 4 US communities. We used Centers for Medicare & Medicaid Services fee-for-service claims codes to identify cases of incident epilepsy starting at or after age 67. We used Cox proportional hazards analysis to identify the hazard of mortality associated with LOE and to adjust for demographics and vascular risk factors. We used death certificate data to identify dates and causes of death.

Results

Analyses included 9,090 participants, of whom 678 developed LOE during median 11.5 years of follow-up after age 67. Participants who developed LOE were at an increased hazard of mortality compared to those who did not, with adjusted hazard ratio 2.39 (95% confidence interval 2.12-2.71). We observed excess mortality due to stroke, dementia, neurologic conditions, and end-stage renal disease in participants with compared to without LOE. Only 4 deaths (1.1%) were directly attributed to seizure-related causes.

Conclusions

Persons who develop LOE are at increased risk of death compared to those without epilepsy, even after adjusting for comorbidities. The majority of this excess mortality is due to stroke and dementia.

SUBMITTER: Johnson EL

PROVIDER: S-EPMC8456359 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Mortality in Patients With Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.

Johnson Emily L EL Krauss Gregory L GL Kucharska-Newton Anna A Lam Alice D AD Sarkis Rani R Gottesman Rebecca F RF

Neurology 20210719 11

<h4>Background and objectives</h4>To determine the risk of mortality and causes of death in persons with late-onset epilepsy (LOE) compared to those without epilepsy in a community-based sample, adjusting for demographics and comorbid conditions.<h4>Methods</h4>This is an analysis of the prospective Atherosclerosis Risk in Communities study, initiated in 1987-1989 among 15,792 mostly Black and White men and women in 4 US communities. We used Centers for Medicare & Medicaid Services fee-for-servi ...[more]

PMID: 34282048

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Project description:IntroductionCognitive phenotyping is a widely used approach to characterize the heterogeneity of deficits in patients with a range of neurological disorders but has only recently been applied to patients with epilepsy. In this study, we identify cognitive phenotypes in older adults with late-onset epilepsy (LOE) and examine their demographic, clinical, and vascular profiles. Further, we examine whether specific phenotypes pose an increased risk for progressive cognitive decline.MethodsParticipants were part of the Atherosclerosis Risk in Communities Study (ARIC), a prospective longitudinal community-based cohort study of 15,792 individuals initially enrolled in 1987-1989. LOE was identified from linked Centers for Medicare and Medicaid Services claims data. Ninety-one participants with LOE completed comprehensive testing either prior to or after seizure onset as part of a larger cohort in the ARIC Neurocognitive Study in either 2011-2013 or 2016-2017 (follow-up mean = 4.9 years). Cognitive phenotypes in individuals with LOE were derived by calculating test-level impairments for each participant (i.e., ≤1 SD below cognitively normal participants on measures of language, memory, and executive function/processing speed); and then assigning participants to phenotypes if they were impaired on at least two tests within a domain. The total number of impaired domains was used to determine the cognitive phenotypes (i.e., Minimal/No Impairment, Single Domain, or Multidomain).ResultsAt our baseline (Visit 5), 36.3% met criteria for Minimal/No Impairment, 35% for Single Domain Impairment (with executive functioning/ processing speed impaired in 53.6%), and 28.7% for Multidomain Impairment. The Minimal/No Impairment group had higher education and occupational complexity. There were no differences in clinical or vascular risk factors across phenotypes. Of those participants with longitudinal data (Visit 6; n = 24), 62.5% declined (i.e., progressed to a more impaired phenotype) and 37.5% remained stable. Those who remained stable were more highly educated compared to those that declined.DiscussionOur results demonstrate the presence of identifiable cognitive phenotypes in older adults with LOE. These results also highlight the high prevalence of cognitive impairments across domains, with deficits in executive function/processing speed the most common isolated impairment. We also demonstrate that higher education was associated with a Minimal/No Impairment phenotype and lower risk for cognitive decline over time.

Project description:ImportanceThe incidence of epilepsy is higher in older age than at any other period of life. Stroke, dementia, and hypertension are associated with late-onset epilepsy; however, the role of other vascular and lifestyle factors remains unclear.ObjectiveTo identify midlife vascular and lifestyle risk factors for late-onset epilepsy.Design, setting, and participantsThe Atherosclerosis Risk in Communities (ARIC) study is a prospective cohort study of 15 792 participants followed up since 1987 to 1989 with in-person visits, telephone calls, and surveillance of hospitalizations (10 974 invited without completing enrollment). The ARIC is a multicenter study with participants selected from 4 US communities. This study included 10 420 black or white participants from ARIC with at least 2 years of Medicare fee-for-service coverage and without missing baseline data. Data were analyzed betweeen April 2017 and May 2018.ExposuresDemographic, vascular, lifestyle, and other possible epilepsy risk factors measured at baseline (age 45-64 years) were evaluated in multivariable survival models including demographics, vascular risk factors, and lifestyle risk factors.Main outcomes and measuresTime to development of late-onset epilepsy (2 or more International Classification of Diseases, Ninth Revision codes for epilepsy or seizures starting at 60 years or older in any claim [hospitalization or outpatient Medicare through 2013]), with first code for seizures after at least 2 years without code for seizures.ResultsOf the 10 420 total participants (5878 women [56.4%] and 2794 black participants [26.8%]; median age 55 years at first visit), 596 participants developed late-onset epilepsy (3.33 per 1000 person-years). The incidence was higher in black than in white participants (4.71; 95% CI, 4.12-5.40 vs 2.88; 95% CI, 2.60-3.18 per 1000 person-years). In multivariable analysis, baseline hypertension (hazard ratio [HR], 1.30; 95% CI, 1.09-1.55), diabetes (HR, 1.45; 95% CI, 1.17-1.80), smoking (HR, 1.09; 95% CI, 1.01-1.17), apolipoprotein E ε4 genotype (1 allele HR, 1.22; 95% CI, 1.02-1.45; 2 alleles HR, 1.95; 95% CI, 1.35-2.81), and incident stroke (HR, 3.38; 95% CI, 2.78-4.10) and dementia (HR, 2.56; 95% CI, 2.11-3.12) were associated with an increased risk of late-onset epilepsy, while higher levels of physical activity (HR, 0.90; 95% CI, 0.83-0.98) and moderate alcohol intake (HR, 0.72; 95% CI, 0.57-0.90) were associated with a lower risk. Results were similar after censoring individuals with stroke or dementia.Conclusions and relevancePotentially modifiable risk factors in midlife and the APOE ε4 genotype were positively associated with risk of developing late-onset epilepsy. Although stroke and dementia were both associated with late-onset epilepsy, vascular and lifestyle risk factors were significant even in the absence of stroke or dementia.

Project description:BackgroundGrowing evidence suggests that the Arg16Arg genotype of the beta-2 adrenergic receptor gene may be associated with adverse effects of beta-agonist therapy. We sought to examine the association of beta-agonist use and the Arg16Gly polymorphism with lung function and mortality among participants in the Atherosclerosis Risk in Communities study.Methodology and principal findingsWe genotyped study participants and analyzed the association of the Arg16Gly polymorphism and beta-agonist use with lung function at baseline and clinical examination three years later and with all-cause mortality during 10 years of follow-up. Lung function was characterized by percent-predicted forced expiratory volume in 1 second. Associations were examined separately for blacks and whites. Black beta-agonist users with the Arg/Arg genotype had better lung function at baseline and at the second clinical visit than those with Arg/Gly and Gly/Gly genotypes. Adjusted mean percent-predicted FEV(1) was 21% higher in Arg/Arg subjects compared to Gly/Gly at baseline (p = 0.01) and 20% higher than Gly/Gly at visit 2 (p = 0.01). Arg/Gly subjects had adjusted percent-predicted FEV(1) 17% lower than Arg/Arg at baseline but were similar to Arg/Arg subjects at visit 2. Although black beta-agonist users with the Arg/Arg genotype appeared to have better crude survival rates, the association between genotype and all-cause mortality was inconclusive. We found no difference in lung function or mortality by genotype among blacks who did not use beta-agonists or among whites, regardless of beta-agonist use.ConclusionsBlack beta-agonist users with the ADRB2 Arg16Arg genotype had better lung function, and, possibly, better overall survival compared to black beta-agonist users with the Gly16Gly genotype. Our findings highlight the need for additional studies of sufficient size and statistical power to allow examination of outcomes among beta-agonist users of different races and genotypes.

Project description:<p>The Atherosclerosis Risk in Communities (ARIC) Study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a prospective epidemiologic study conducted in four U.S. communities. The four communities are Forsyth County, NC; Jackson, MS; the northwest suburbs of Minneapolis, MN; and Washington County, MD. ARIC is designed to investigate the etiology and natural history of atherosclerosis, the etiology of clinical atherosclerotic diseases, and variation in cardiovascular risk factors, medical care and disease by race, gender, location, and date.</p> <p>ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community. A total of 15,792 participants received an extensive examination, including medical, social, and demographic data. These participants were reexamined every three years with the first screen (baseline) occurring in 1987-89, the second in 1990-92, the third in 1993-95, and the fourth and last exam was in 1996-98. Follow-up occurs yearly by telephone to maintain contact with participants and to assess health status of the cohort.</p> <p>In the Community Surveillance Component, currently ongoing, these four communities are investigated to determine the community-wide occurrence of hospitalized myocardial infarction and coronary heart disease deaths in men and women aged 35-84 years. Hospitalized stroke is investigated in cohort participants only. Starting in 2006, the study conducts community surveillance of inpatient (ages 55 years and older) and outpatient heart failure (ages 65 years and older) for heart failure events beginning in 2005.</p> <p>ARIC is currently funded through January 31, 2012.</p> <p>This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to atherosclerosis and cardiovascular disease through large-scale genome-wide association studies of well-characterized cohorts of adults in four defined populations. Genotyping was performed at the Broad Institute of MIT and Harvard, a GENEVA genotyping center. Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.</p>

Project description:BackgroundPublic health recommendations on the benefits and harms of moderate alcohol intake require a thorough and unbiased understanding of all potential effects of various levels and patterns of alcohol consumption. We seek to evaluate the associations between patterns of current and past alcohol consumption with hospitalizations and mortality.MethodsData came from a prospective cohort of 12,327 adults (56% women, 78% white, mean age 60 years) participating in the Atherosclerosis Risk in Communities study visit 3 (1993 to 1995). Current and past alcohol consumption was based on self-report. Hospitalizations and mortality were ascertained through December 31, 2017. Negative binomial and Cox proportional hazards regressions were used.Results24.8% of the study population reported never drinking, 48.3% reported currently drinking without a history of heavy drinking, 4.2% reported currently drinking with a history of heavy drinking, 19.2% reported being former drinkers without a history of heavy drinking, and 3.4% reported being former drinkers with a history of heavy drinking. Compared to those who reported drinking ≤1 to 7 drinks/wk, never drinkers (incident rate ratio [IRR]: 1.21 (95% confidence interval 1.13, 1.29) and former drinkers with (IRR: 1.43 [1.26, 1.63]) or without (IRR: 1.21 [1.13, 1.30]) a history of heavy drinking had a positive association with all-cause hospitalization (p < 0.001). Those who reported drinking ≤1 to 7 drinks/wk had the lowest all-cause mortality rate (19.2 per 1,000 person-years [18.4, 20.1]) and former drinkers with a history of heavy drinking had the highest (43.7 per 1,000 person-years [39.0, 49.1]).ConclusionsThe positive associations with hospitalization and mortality were stronger among never and former drinkers compared to those who consume ≤1 to 7 drinks/wk. Former drinkers with a history of heavy drinking had a stronger positive association with adverse health outcomes than former drinkers without a history of heavy drinking, highlighting the impact of this pattern of alcohol consumption.

Dataset Information

Mortality in Patients With Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.

Background and objectives

Methods

Results

Conclusions

Publications

Mortality in Patients With Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.

Similar Datasets

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