Dataset Information

Late-onset epilepsy and 25-year cognitive change: The Atherosclerosis Risk in Communities (ARIC) study.

ABSTRACT:

Objective

To define the association between late-onset epilepsy (LOE) and 25-year change in cognitive performance.

Methods

The Atherosclerosis Risk in Communities (ARIC) study is a multicenter longitudinal cohort study with participants from four U.S. communities. From linked Medicare claims, we identified cases of LOE, defined as ≥2 seizure-related diagnostic codes starting at age ≥67. The ARIC cohort underwent evaluation with in-person visits at intervals of 3-15 years. Cognition was evaluated 4 times over >25 years (including before the onset of seizures) using the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT); a global z-score was also calculated. We compared the longitudinal cognitive changes of participants with and without LOE, adjusting for demographics and LOE risk factors.

Results

From 8033 ARIC participants with midlife cognitive testing and Medicare claims data available (4523 [56%] female, 1392 [17%] Black), we identified 585 cases of LOE. The rate of cognitive decline was increased on all measures in the participants who developed LOE compared to those without LOE. On the measure of global cognition, participants with LOE declined by -0.43 z-score points more over 25 years than did participants without epilepsy (95% confidence interval [CI] -0.59 to -0.27). Prior to the onset of seizures, cognitive decline was more rapid on the DWRT, DSST, and global z-scores in those who would later develop LOE than it was in non-LOE participants. Results were similar after excluding data from participants with dementia.

Significance

Global cognition, verbal memory, executive function, and word fluency declined faster over time in persons developing LOE than without LOE. Declines in cognition preceding LOE suggest these are linked; it will be important to investigate causes for midlife cognitive declines associated with LOE.

SUBMITTER: Johnson EL

PROVIDER: S-EPMC7718433 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:Importance:Vascular risk factors have been associated with cognitive decline. Midlife exposure to these factors may be most important in conferring late-life risk of cognitive impairment. Objectives:To examine Atherosclerosis Risk in Communities (ARIC) participants in midlife and to explore associations between midlife vascular risk factors and 25-year dementia incidence. Design, Setting, and Participants:This prospective cohort investigation of the Atherosclerosis Risk in Communities (ARIC) Study was conducted from 1987-1989 through 2011-2013. The dates of this analysis were April 2015 through August 2016. The setting was ARIC field centers (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). The study comprised 15?744 participants (of whom 27.1% were black and 72.9% white) who were aged 44 to 66 years at baseline. Main Outcomes and Measures:Demographic and vascular risk factors were measured at baseline (obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia) as well as presence of the APOE ?4 genotype. After the baseline visit, participants had 4 additional in-person visits, for a total of 5 in-person visits, hospitalization surveillance, telephone calls, and repeated cognitive evaluations. Most recently, in 2011-2013, through the ARIC Neurocognitive Study (ARIC-NCS), participants underwent a detailed neurocognitive battery, informant interviews, and adjudicated review to define dementia cases. Additional cases were identified through the Telephone Interview for Cognitive Status-Modified or informant interview, for participants not attending the ARIC-NCS visit, or by an International Classification of Diseases, Ninth Revision dementia code during a hospitalization. Fully adjusted Cox proportional hazards regression was used to evaluate associations of baseline vascular and demographic risk factors with dementia. Results:In total, 1516 cases of dementia (57.0% female and 34.9% black, with a mean [SD] age at visit 1 of 57.4 [5.2] years) were identified among 15 744 participants. Black race (hazard ratio [HR], 1.36; 95% CI, 1.21-1.54), older age (HR, 8.06; 95% CI, 6.69-9.72 for participants aged 60-66 years), lower educational attainment (HR, 1.61; 95% CI, 1.28-2.03 for less than a high school education), and APOE ?4 genotype (HR, 1.98; 95% CI, 1.78-2.21) were associated with increased risk of dementia, as were midlife smoking (HR, 1.41; 95% CI, 1.23-1.61), diabetes (HR, 1.77; 95% CI, 1.53-2.04), prehypertension (HR, 1.31; 95% CI, 1.14-1.51), and hypertension (HR, 1.39; 95% CI, 1.22-1.59). The HR for dementia for diabetes was almost as high as that for APOE ?4 genotype. Conclusions and Relevance:Midlife vascular risk factors are associated with increased risk of dementia in black and white ARIC Study participants. Further studies are needed to evaluate the mechanism of and opportunities for prevention of the cognitive sequelae of these risk factors in midlife.

Project description:BACKGROUND:Previous studies suggest that heart failure (HF) is an independent risk factor for cognitive decline. A better understanding of the relationship between HF, cognitive status, and cognitive decline in a community-based sample may help clinicians understand disease risk. OBJECTIVE:To examine whether persons with HF have a higher prevalence of cognitive impairment and whether persons developing HF have more rapid cognitive decline. DESIGN:This observational cohort study of American adults in the Atherosclerosis Risk in Communities (ARIC) study has two components: cross-sectional analysis examining the association between prevalent HF and cognition using multinomial logistic regression, and change over time analysis detailing the association between incident HF and change in cognition over 15 years. PARTICIPANTS:Among visit 5 (2011-2013) participants (median age 75 years), 6495 had neurocognitive information available for cross-sectional analysis. Change over time analysis examined the 5414 participants who had cognitive scores and no prevalent HF at visit 4 (1996-1998). MEASUREMENTS:The primary outcome was cognitive status, classified as normal, mild cognitive impairment [MCI], and dementia on the basis of standardized cognitive tests (delayed word recall, word fluency, and digit symbol substitution). Cognitive change was examined over a 15-year period. Control variables included socio-demographic, vascular, and smoking/drinking measures. RESULTS:At visit 5, participants with HF had a higher prevalence of dementia (adjusted relative risk ratio [RRR] = 1.60 [95% CI 1.13, 2.25]) and MCI (RRR = 1.36 [1.12, 1.64]) than those without HF. A decline in cognition between visits 4 and 5 was - 0.07 standard deviation units [- 0.13, - 0.01] greater among persons who developed HF compared to those who did not. Results did not differ by ejection fraction. CONCLUSION:HF is associated with neurocognitive dysfunction and decline independent of other co-morbid conditions. Further study is needed to determine the underlying pathophysiology.

Project description:Importance:The 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. Objective:To identify midlife vascular and lifestyle risk factors for late-onset epilepsy. Design, Setting, and Participants:The 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. Exposures:Demographic, 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 Measures:Time 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. Results:Of 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 ?4 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 Relevance:Potentially modifiable risk factors in midlife and the APOE ?4 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:Hypertension is a treatable potential cause of cognitive decline and dementia, but its greatest influence on cognition may occur in middle age.To evaluate the association between midlife (48-67 years of age) hypertension and the 20-year change in cognitive performance.The Atherosclerosis Risk in Communities cohort (1990-1992 through 2011-2013) underwent evaluation at field centers in Washington County, Maryland, Forsyth County, North Carolina, Jackson, Mississippi, and the Minneapolis, Minnesota, suburbs. Of 13?476 African American and white participants with baseline cognitive data, 58.0% of living participants completed the 20-year cognitive follow-up.Hypertension, prehypertension, or normal blood pressure (BP) at visit 2 (1990-1992) constituted the primary exposure. Systolic BP at visit 2 or 5 (2011-2013) and indication for treatment at visit 2 based on the Eighth Joint National Committee (JNC-8) hypertension guidelines constituted the secondary exposures.Prespecified outcomes included the 20-year change in scores on the Delayed Word Recall Test, Digit Symbol Substitution Test, and Word Fluency Test and in global cognition.During 20 years, baseline hypertension was associated with an additional decline of 0.056 global z score points (95% CI, -0.100 to -0.012) and prehypertension was associated nonsignificantly with 0.040 more global z score points of decline (95% CI, -0.085 to 0.005) compared with normal BP. Individuals with hypertension who used antihypertensives had less decline during the 20 years than untreated individuals with hypertension (-0.050 [95% CI, -0.003 to -0.097] vs -0.079 [95% CI, -0.156 to -0.002] global z score points). Having a JNC-8-specified indication for initiating antihypertensive treatment at baseline was associated with a greater 20-year decline (-0.044 [95% CI, -0.085 to -0.003] global z score points) than not having an indication. We observed effect modification by race for the continuous systolic BP analyses (P?=?.01), with each 20-mm Hg increment at baseline associated with an additional decline of 0.048 (95% CI, -0.074 to -0.022) points in global cognitive z score in whites but not in African Americans (decline, -0.020 [95% CI, -0.026 to 0.066] points). Systolic BP at the end of follow-up was not associated with the preceding 20 years of cognitive change in either group. Methods to account for bias owing to attrition strengthened the magnitude of some associations.Midlife hypertension and elevated midlife but not late-life systolic BP was associated with more cognitive decline during the 20 years of the study. Greater decline is found with higher midlife BP in whites than in African Americans.