Trends in Stroke Incidence Rates in Older US Adults: An Update from the Atherosclerosis Risk in Communities (ARIC) Cohort Study

Importance: Determining whether the previously reported decreased stroke incidence rates from 1987 to 2011 among US adults 65 years and older in the Atherosclerosis Risk in Communities (ARIC) study continued to decrease subsequently can help guide policy and planning efforts. Objective: To evaluate whether stroke incidence declines among older adults in the ARIC study continued after 2011. Design, Setting, and Participants: ARIC is a community-based prospective cohort study including 15792 individuals aged 45 to 64 years at baseline (1987-1989), selected by probability sampling from residents of Forsyth County, North Carolina; Jackson, Mississippi (black individuals only); the northwestern suburbs of Minneapolis, Minneapolis; and Washington County, Maryland (ie, center). The present study included ARIC participants free of stroke at baseline, followed up through December 31, 2017. Data were collected through personal interviews and physical examinations during study visits, annual/semiannual telephone interviews, and active surveillance of discharges from local hospitals. Stroke events were adjudicated by study-physicians reviewers. Analysis began September 2018. Main Outcomes and Measures: The main outcome was stroke incidence rates, which were computed with 95% CIs stratifying the analysis by age and calendar time. Trends in adjusted incidence rates were assessed using Poisson regression incidence rate ratios. Models included calendar time, age, sex, race/center, and time-varying risk factors (hypertension, diabetes, coronary heart disease, cholesterol-lowering medication use, and smoking). Results: Of 14357 ARIC participants with 326654 person-years of follow-up, the mean (SD) age at baseline was 54.1 (5.8) years and 7955 (55.4%) were women. From 1987 to 2017, a total of 1340 incident strokes occurred among ARIC participants, and among them, 1028 (76.7%) occurred in participants 65 years and older. Crude incidence rates of stroke for participants 65 years and older decreased progressively from 1987 to 2017. Incidence rates, adjusted for age, sex, race/center, and time-varying risk factors, decreased by 32% (95% CI, 23%-40%) per 10 years in participants 65 years and older. Findings were consistent across decades, sex, and race. Conclusions and Relevance: Validated total stroke incidence rates in adults 65 years and older decreased over the last 30 years in the ARIC cohort. The decrease in rates previously reported for 1987 to 2011 extends for the subsequent 6 years in men and women as well as in white and black individuals

Stroke Incidence and Survival in American Indians, Blacks, and Whites: The Strong Heart Study and Atherosclerosis Risk in Communities Study

Background: American Indians (AIs) have high stroke morbidity and mortality. We compared stroke incidence and mortality in AIs, blacks, and whites. Methods and Results: Pooled data from 2 cardiovascular disease cohort studies included 3182 AIs from the SHS (Strong Heart Study), aged 45 to 74 years at baseline (1988–1990) and 3765 blacks and 10 413 whites from the ARIC (Atherosclerosis Risk in Communities) Study, aged 45 to 64 years at baseline (1987–1989). Stroke surveillance was based on self-report, hospital records, and death certificates. We estimated hazard ratios for incident stroke (ischemic and hemorrhagic combined) through 2008, stratified by sex and birth-year tertile, and relative risk for poststroke mortality. Incident strokes numbered 282 for AIs, 416 for blacks, and 613 for whites. For women and men, stroke incidence among AIs was similar to or lower than blacks and higher than whites. Covariate adjustment resulted in lower hazard ratios for most comparisons, but results for these models were not always statistically significant. After covariate adjustment, AI women and men had higher 30-day poststroke mortality than blacks (relative risk=2.1 [95% CI=1.0, 3.2] and 2.2 [95% CI=1.3, 3.1], respectively), and whites (relative risk=1.6 [95% CI=0.8, 2.5] and 1.7 [95% CI=1.1, 2.4]), and higher 1-year mortality (relative risk range=1.3–1.5 for all comparisons). Conclusions: Stroke incidence in AIs was lower than for blacks and higher than for whites; differences were larger for blacks and smaller for whites after covariate adjustment. Poststroke mortality was higher in AIs than blacks and whites

Midlife systemic inflammation is associated with frailty in later life: The ARIC study

Background: Evidence suggests that systemic inflammation may have a mechanistic role in age-related frailty, yet prospective data is limited. We examined whether systemic inflammation during midlife was associated with late-life frailty within the community-based Atherosclerosis Risk in Communities Study. Methods: Plasma levels of four inflammatory markers (fibrinogen, von Willebrand factor, and Factor VIII, and white blood cell count) were measured during Visit 1 (1987-1989; mean age: 52 [5]), standardized into z-scores, and combined to create an inflammation composite score. High-sensitivity C-reactive protein (CRP) was measured 3 (Visit 2, 1990-1992) and 9 (Visit 4, 1996-1999) years later. Frailty was evaluated in 5,760 participants during late life (Visit 5, 2011-2013; mean age: 75 [5]). Analyses were adjusted for demographic and physiological variables, and midlife medical comorbidity using logistic regression. Results: A 1 SD increase in midlife inflammation composite score was associated with higher odds of frailty 24 years later (odds ratio [OR] = 1.39, 95% confidence interval [CI]: 1.18-1.65). Similarly, each standard deviation increase in Visit 2 CRP (OR = 1.24, 95% CI: 1.09-1.40) and Visit 4 CRP (OR = 1.35, 95% CI: 1.19-1.53) was associated with a higher odds of frailty 21 and 15 years later. Participants who maintained elevated CRP (≥3 mg/L) at Visits 2 and 4 or transitioned to a state of elevated CRP during this period were more likely to subsequently meet frailty criteria compared to those who maintained low CRP. These associations were stronger among white, compared to African American, participants (p-interactions <.038). Conclusions: Systemic inflammation during midlife may independently promote pathophysiological changes underlying frailty in a subset of the population

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

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

Interaction-free generation of entanglement

In this paper, we study how to generate entanglement by interaction-free measurement. Using Kwiat et al.'s interferometer, we construct a two-qubit quantum gate that changes a particle's trajectory according to the other particle's trajectory. We propose methods for generating the Bell state from an electron and a positron and from a pair of photons by this gate. We also show that using this gate, we can carry out the Bell measurement with the probability of 3/4 at the maximum and execute a controlled-NOT operation by the method proposed by Gottesman and Chuang with the probability of 9/16 at the maximum. We estimate the success probability for generating the Bell state by our procedure under imperfect interaction.Comment: 18 pages, Latex2e, 11 eps figures, v2: minor corrections and one reference added, v3: a minor correctio

Cognitive Decline and Oral Health in Middle-aged Adults in the ARIC Study

Even before dementia becomes apparent, cognitive decline may contribute to deterioration in oral health. This cohort study of middle-aged adults evaluated associations of six-year change in cognitive function with oral health behaviors and conditions in the Atherosclerosis Risk in Communities (ARIC) study. Cognitive function was measured at study visits in 1990-1992 and 1996-1998 with three tests: (a) Delayed Word Recall (DWR), (b) Digit Symbol Substitution (DSS), and (c) Word Fluency (WF). Cognitive decline scores were computed as ‘studentized’ residuals of 1996-1998 scores regressed against 1990-1992 scores. In 1996-1998, 10,050 participants answered dental screening questions, and 5,878 of 8,782 dentate participants received a comprehensive oral examination. Multiple regression models used cognitive change to predict oral health behaviors and conditions with adjustment for covariates. In the fully adjusted models, greater decline in all three measures of cognitive function was associated with increased odds of complete tooth loss. Greater decline in DSS and WF scores was associated with infrequent toothbrushing. Decline in WF scores was also associated with higher plaque levels. In these middle-aged adults, six-year cognitive decline was modestly associated with less frequent toothbrushing, plaque deposit, and greater odds of edentulism, but not with other oral behaviors or diseases

Unified criterion for security of secret sharing in terms of violation of Bell inequality

In secret sharing protocols, a secret is to be distributed among several partners so that leaving out any number of them, the rest do not have the complete information. Strong multiqubit correlations in the state by which secret sharing is carried out, had been proposed as a criterion for security of such protocols against individual attacks by an eavesdropper. However we show that states with weak multiqubit correlations can also be used for secure secret sharing. That our state has weak multiqubit correlations, is shown from the perspective of violation of local realism, and also by showing that its higher order correlations are described by lower ones. We then present a unified criterion for security of secret sharing in terms of violation of local realism, which works when the secret sharing state is the Greenberger-Horne-Zeilinger state (with strong multiqubit correlations), as well as states of a different class (with weak multiqubit correlations).Comment: 7 pages, no figures, RevTeX

Subclinical Vascular Disease Burden and Premature Mortality Among Middle-aged Adults: the Atherosclerosis Risk in Communities Study

Background: Whether high burden of subclinical vascular disease (SVD) is associated with increased premature mortality among middle-aged adults is not adequately understood. The association of midlife SVD burden with premature mortality among middle-aged adults free of clinical cardiovascular disease (CVD) could provide further insights into stratifying premature death beyond clinical CVD. Objective: To determine whether high burden of subclinical vascular disease is associated with increased premature mortality among middle-aged adults. Design: We leveraged data from the Atherosclerosis Risk in Communities Study. Participants: Thirteen thousand eight hundred seventy-six community-dwelling blacks and whites aged 45–64 years from the Atherosclerosis Risk in Communities Study. Main Measures: Each SVD measure—ankle-brachial index, carotid intima-media thickness, and electrocardiogram—was scored 0 (no abnormalities), 1 (minor abnormalities), or 2 (major abnormalities). An index was constructed as the sum of three measures, ranging from 0 (lowest burden) to 6 (highest burden). We used the Cox proportional-hazards model to determine the association of SVD burden with premature mortality (death before age 70) among persons free of clinical CVD. We then tested the difference in point estimates between SVD and clinical CVD. Key Results: Among persons without CVD, the premature death was 1.7, 2.1, 2.5, and 3.8 per 1000 person-years among those with an SVD score of 0 (lowest burden), 1, 2, and 3–6 (highest burden), respectively. After multivariable-adjustment, highest SVD burden (score = 3–6; HR = 1.47) was significantly associated with premature death among persons initially without CVD. In the model where persons with and without CVD were included, high SVD burden (score: 3–6 vs. 0) and CVD did not have hugely different association with premature death (HR = 1.49 vs. 1.68; P = 0.32 for comparison). Conclusions: Midlife SVD burden was associated with premature mortality and it could stratify premature death beyond clinical CVD. It is important to take SVD into account when designing interventions for reducing premature mortality

Association between white matter hyperintensities, cortical volumes, and late-onset epilepsy

ObjectiveTo identify the association between brain vascular changes and cortical volumes on MRI and late-onset epilepsy.MethodsIn 1993-1995, 1,920 participants (median age 62.7, 59.9% female) in the community-based Atherosclerosis Risk in Communities (ARIC) Study underwent MRI, and white matter hyperintensities were measured. In addition, in 2011-2013, 1,964 ARIC participants (median age 72.4, 61.1% female) underwent MRI, and cortical volumes and white matter hyperintensities were measured. We identified cases of late-onset epilepsy (starting at age 60 or later) from ARIC hospitalization records and Medicare claims data. Using the 1993-1995 MRI, we evaluated the association between white matter hyperintensities and subsequent epilepsy using survival analysis. We used the 2011-2013 MRI to conduct cross-sectional logistic regression to examine the association of cortical volumes and white matter hyperintensities with late-onset epilepsy. All models were adjusted for demographics, hypertension, diabetes, smoking, and APOE ϵ4 allele status.ResultsNinety-seven ARIC participants developed epilepsy after having an MRI in 1993-1995 (incidence 3.34 per 1,000 person-years). The degree of white matter hyperintensities measured at ages 49-72 years was associated with the risk of late-onset epilepsy (hazard ratio 1.27 per age-adjusted SD, 95% confidence interval [CI] 1.06-1.54). Lower cortical volume scores were associated cross-sectionally with higher odds of late-onset epilepsy (odds ratio 1.87, 95% CI 1.16-3.02) per age-adjusted SD.ConclusionsThis study demonstrates associations between earlier-life white matter hyperintensities on MRI and later-life incident epilepsy, and between cortical volumes measured later in life and late-onset epilepsy. These findings may help illuminate the causes of late-onset epilepsy

Association of Hospitalization, Critical Illness, and Infection with Brain Structure in Older Adults

Objectives: To examine the association between hospitalization, critical illness, and infection occurring during middle- and late-life and structural brain abnormalities in older adults. Design: Prospective cohort study. Setting: Atherosclerosis Risk in Communities (ARIC) Study. Participants: A community sample of adults who were 44 to 66 years of age at study baseline. Measurements: Active surveillance of local hospitals and annual participant contact were used to gather hospitalization information (including International Classification of Diseases, Ninth Revision, codes) on all participants over a 24-year surveillance period. Subsequently, a subset of participants underwent 3-Tesla brain magnetic resonance imaging (MRI) to quantify total and regional brain volumes, white matter hyperintensity (WMH) volume, and white matter microstructural integrity (fractional anisotropy (FA) and mean diffusivity (MD) as measured using diffusion tensor imaging (DTI)). Results: Of the 1,689 participants included (mean age at MRI 76±5), 72% were hospitalized, 14% had a major infection, and 4% had a critical illness during the surveillance period. Using covariate-adjusted regression, hospitalization was associated with 0.12–standard deviation (SD) greater WMH volume (95% confidence interval (CI)=0.00–0.24) and poorer white matter microstructural integrity (0.17-SD lower FA, 95% CI=–0.27 to –0.06; 0.16-SD greater MD, 95% CI=0.07–0.25) than no hospitalization. There was a dose-dependent relationship between number of hospitalizations, smaller brain volumes, and lower white matter integrity (p-trends ≤.048). In hospitalized participants, critical illness was associated with smaller Alzheimer's disease (AD) signature region (–1.64 cm3, 95% CI=–3.16 to –0.12); major infection was associated with smaller AD signature region (–1.28 cm3, 95% CI=–2.21 to –0.35) and larger ventricular volume (3.79 cm3, 95% CI= 0.81–6.77). Conclusions: Whereas all-cause hospitalization was primarily associated with lower white matter integrity, critical illness and major infection were associated with smaller brain volume, particularly within regions implicated in AD