Social relationships, amyloid burden, and dementia: The ARIC-PET study.

INTRODUCTION: This study aimed to assess whether social relationships in mid-life reduce the risk of dementia related to amyloid burden. METHODS: Participants in the Atherosclerosis Risk in Communities (ARIC) study were assessed for social support and isolation (visit 2; 1990-1992). A composite measure, "social relationships," was generated. Brain amyloid was evaluated with florbetapir positron emission tomography (PET); (visit 5; 2012-2014). Incident dementia cases were identified following visit 5 through 2019 using ongoing surveillance. Relative contributions of mid-life social relationships and elevated brain amyloid to incident dementia were evaluated with Cox regression models. RESULTS: Among 310 participants without dementia, strong mid-life social relationships were associated independently with lower dementia risk. Elevated late-life brain amyloid was associated with greater dementia risk. DISCUSSION: Although mid-life social relationships did not moderate the relationship between amyloid burden and dementia, these findings affirm the importance of strong social relationships as a potentially protective factor against dementia.

Orthostatic Blood Pressure Change, Dizziness, and Risk of Dementia in the ARIC Study.

BACKGROUND: Abnormal orthostatic blood pressure (BP) regulation may result in cerebral hypoperfusion and brain ischemia and contribute to dementia. It may also manifest as early symptoms of the neurodegenerative process associated with dementia. The relationship between the magnitude and timing of orthostatic BP responses and dementia risk is not fully understood. METHODS: We conducted a prospective cohort analysis of the associations of orthostatic BP changes and self-reported orthostatic dizziness with the risk of dementia in the Atherosclerosis Risk in Communities study (ARIC). We calculated changes in BP from the supine to the standing position at 5 measurements taken within 2 minutes after standing during the baseline visit (1987-1989). The primary outcome was adjudicated dementia ascertained through 2019. RESULTS: Among 11 644 participants (mean [SD] age, 54.5 [5.7] years; 54.1% women; 25.9% Black), 2303 dementia cases were identified during a median follow-up of 25.9 years. Large decreases in systolic BP from the supine to standing position measured at the first 2 measurements ≈30 and 50 seconds after standing, but not afterward, were associated with orthostatic dizziness and a higher risk of dementia. Comparing a decrease in systolic BP of ≤-20 or >-20 to -10 mm Hg to stable systolic BP (>-10 to 10 mm Hg) at the first measurement, the adjusted hazard ratios were 1.22 (95% CI, 1.01-1.47) and 1.10 (95% CI, 0.97-1.25), respectively. CONCLUSIONS: Abnormal orthostatic BP regulation, especially abrupt drops in BP within the first minute, might be early risk markers for the development of dementia. Transient early orthostatic hypotension warrants more attention in clinical settings.

The association of long-term exposure to criteria air pollutants, fine particulate matter components, and airborne trace metals with late-life brain amyloid burden in the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Studies suggest associations between long-term ambient air pollution exposure and outcomes related to Alzheimer's disease (AD). Whether a link exists between pollutants and brain amyloid accumulation, a biomarker of AD, is unclear. We assessed whether long-term air pollutant exposures are associated with late-life brain amyloid deposition in Atherosclerosis Risk in Communities (ARIC) study participants. METHODS: We used a chemical transport model with data fusion to estimate ambient concentrations of PM2.5 and its components, NO2, NOx, O3 (24-hour and 8-hour), CO, and airborne trace metals. We linked concentrations to geocoded participant addresses and calculated 10-year mean exposures (2002 to 2011). Brain amyloid deposition was measured using florbetapir amyloid positron emission tomography (PET) scans in 346 participants without dementia in 2012-2014, and we defined amyloid positivity as a global cortical standardized uptake value ratio ≥ the sample median of 1.2. We used logistic regression models to quantify the association between amyloid positivity and each air pollutant, adjusting for putative confounders. In sensitivity analyses, we considered whether use of alternate air pollution estimation approaches impacted findings for PM2.5, NO2, NOx, and 24-hour O3. RESULTS: At PET imaging, eligible participants (N = 318) had a mean age of 78 years, 56% were female, 43% were Black, and 27% had mild cognitive impairment. We did not find evidence of associations between long-term exposure to any pollutant and brain amyloid positivity in adjusted models. Findings were materially unchanged in sensitivity analyses using alternate air pollution estimation approaches for PM2.5, NO2, NOx, and 24-hour O3. CONCLUSIONS: Air pollution may impact cognition and dementia independent of amyloid accumulation, though whether air pollution influences AD pathogenesis later in the disease course or at higher exposure levels deserves further consideration.

Educational Attainment and Dementia: Mediation by Mid-Life Vascular Risk Factors.

INTRODUCTION: Lower education is associated with higher burden of vascular risk factors in mid-life and higher risk of dementia in late life. We aim to understand the causal mechanism through which vascular risk factors potentially mediate the relationship between education and dementia. METHODS: In a cohort of 13,368 Black and White older adults in the Atherosclerosis Risk in Communities Study, we assessed the relationship between education (grade school, high school without graduation, high school graduate or equivalent, college, graduate/professional school) and dementia among all participants and among those with incident stroke. Cox models were adjusted for age, race-center (a variable stratified by race and field center), sex, apolipoprotein E (APOE) ε4 genotype, and family history of cardiovascular disease. Causal mediation models assessed mediation by mid-life systolic blood pressure, fasting blood glucose, body mass index, and smoking. RESULTS: More education was associated with 8 to 44% lower risk of dementia compared to grade school-level education in a dose-response pattern, while the relationship between education and post-stroke dementia was not statistically significant. Up to 25% of the association between education and dementia was mediated through mid-life vascular risk factors, with a smaller percentage mediated for lower levels of education. INTERPRETATION: A substantial proportion of the relationship between education and dementia was mediated through mid-life vascular risk factors. However, risk factor modification is unlikely to fully address the large educational disparities in dementia risk. Prevention efforts must also address disparities in socioeconomic resources leading to divergent early-life education and other structural determinants of mid-life vascular risk factors. ANN NEUROL 2023;94:13-26.

Positive aspects of caregiving in incident and long-term caregivers: Role of social engagement and distress.

OBJECTIVES: Positive caregiver adaptation over time may be associated with reports of positive aspects of caregiving (PAC). We examined differences in PAC by caregiving duration and social engagement, controlling for measures of distress. METHODS: Participants included 283 African American or White caregivers from the Caregiving Transitions Study with a wide range of caregiving durations. PAC are defined as positive appraisals that caregivers report about their role, such as feeling appreciated or confident. We fit multivariable linear models with the total PAC score as the outcome to assess its association with years of caregiving and social engagement (social network, monthly social contact). Models were adjusted for age, sex, race, marital status, relationship to care recipient, care recipient's dementia status, perceived stress and caregiving strain. RESULTS: Caregivers with higher social engagement reported significantly higher PAC. A non-significant trend was found in most analytic models for caregivers with longer duration of care to report higher PAC. African American caregivers reported higher PAC compared to White caregivers. Dementia caregivers reported lower PAC than non-dementia caregivers in models adjusting for demographics and social network size, but the association was attenuated with the addition of caregiving strain. DISCUSSION: Higher social engagement and longer duration of care tend to be associated with higher PAC after adjusting for demographics and measures of distress. Future studies should aim to leverage longitudinal data to understand whether caregivers shift appraisal to positive aspects of their role and explore implementation of caregiving interventions targeting PAC in order to improve the caregiving experience.

Temporal trends and rural-urban disparities in cerebrovascular risk factors, in-hospital management and outcomes in ischaemic strokes in China from 2005 to 2015: a nationwide serial cross-sectional survey.

BACKGROUND: Stroke is the leading cause of mortality in China, with limited evidence of in-hospital burden obtained from nationwide surveys. We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors, management and outcomes from 2005 to 2015. METHODS: We used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005, 2010 and 2015. We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach. We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015. RESULTS: We analysed 28 277 ischaemic stroke admissions from 189 participating hospitals. From 2005 to 2015, the estimated national hospital admission rate for ischaemic stroke per 100 000 people increased (from 75.9 to 402.7, Ptrend<0.001), and the prevalence of risk factors, including hypertension, diabetes, dyslipidaemia and current smoking, increased. The composite score of diagnostic tests for stroke aetiology assessment (from 0.22 to 0.36, Ptrend<0.001) and secondary prevention treatments (from 0.46 to 0.70, Ptrend<0.001) were improved. A temporal decrease was found in discharge against medical advice (DAMA) (from 15.2% (95% CI 13.7% to 16.7%) to 8.6% (8.1% to 9.0%); adjusted Ptrend=0.046), and decreases in in-hospital mortality (0.7% in 2015 vs 1.8% in 2005; adjusted OR (aOR) 0.52; 95% CI 0.32 to 0.85) and the composite outcome of in-hospital mortality or DAMA (8.4% in 2015 vs 13.9% in 2005; aOR 0.65; 95% CI 0.47 to 0.89) were observed. Disparities between rural and urban hospitals narrowed; however, disparities persisted in in-hospital management (brain MRI: rural-urban difference from -14.4% to -11.2%; cerebrovascular assessment: from -20.3% to -16.7%; clopidogrel: from -2.1% to -10.3%; anticoagulant for atrial fibrillation: from -10.9% to -8.2%) and in-hospital outcomes (DAMA: from 2.7% to 5.0%; composite outcome of in-hospital mortality or DAMA: from 2.4% to 4.6%). CONCLUSIONS: From 2005 to 2015, improvements in hospital admission and in-hospital management for ischaemic stroke in China were found. A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed. Disparities between rural and urban hospitals generally narrowed but persisted.

Pre-stroke dementia and in-hospital outcomes in the Chinese Stroke Center Alliance.

Background: Little is known about the impact of prevalent dementia on in-hospital outcomes of patients with incident stroke in China. Using data from the Chinese Stroke Center Alliance (CSCA), we aim to quantify the prevalence of pre-stroke dementia and whether this group is at higher risk of adverse in-hospital outcomes compared to those without pre-stroke dementia. Methods: We used multivariable logistic regression models to assess the associations between pre-stroke dementia and ambulation by day 2, in-hospital mortality, in-hospital complications, and being discharged home. Covariates included age, sex, comorbidities [dyslipidemia, atrial fibrillation, peripheral vascular disease (PVD), smoking, and alcohol use], medication history (antiplatelet drugs or lipid-lowering drugs), stroke severity [measured by the National Institute of Health Stroke Scale (NIHSS)], administration of intravenous tissue plasminogen activator (IV tPA) within 4.5 hours of stroke onset, and receipt of deep vein thrombosis (DVT) prophylaxis if indicated. Results: In the final analytic sample of 559,070 ischemic stroke patients with no prior stroke history enrolled across 1,476 hospitals, those with pre-stroke dementia (n=1,511; 0.3%) were older and more likely to be female. Despite having received similar treatment, patients with pre-stroke dementia had lower odds of ambulating by day 2 [odds ratio (OR) =0.69; 95% confidence interval (CI): 0.62-0.78], higher odds of in-hospital mortality (OR =2.01; 95% CI: 1.35-2.99) or complications (OR =2.17; 95% CI: 1.93-2.44), and lower odds of being discharged home compared to those without pre-stroke dementia (OR =0.71; 95% CI: 0.62-0.83). Conclusions: Worse in-hospital outcomes among patients with pre-stroke dementia may be explained by pre-existing cognitive impairment that limited their ability to advocate for care needs. Further research is needed to determine whether a different care pathway or additional attention from clinicians is necessary for patients with pre-stroke dementia.

Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021.

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID). Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration. Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022. Exposures: Symptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age. Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months. Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

Eliminating racial disparities in dementia risk by equalizing education quality: A sensitivity analysis.

BACKGROUND: Higher risk of dementia among racial/ethnic minorities compared to White populations in the U.S. has been attributed to life-course exposures to adverse conditions such as lower educational attainment, but most studies have not considered additional disparities in education quality. We sought to determine the extent to which disparities in dementia would be reduced had different racial groups received the same quality of education, with no change to present disparities in educational attainment. METHODS: We conducted a literature review to assess whether and how measures of educational attainment and quality are utilized in the development of norms for standard cognitive screening measures. In a separate search of the literature, we identified estimates of relationships between race, education quality and dementia; and calculated the adjusted association between race and dementia had education quality been equalized between Black and White participants. RESULTS: Most norms for cognitive measures included educational attainment, but few addressed quality. Our search identified relevant parameter estimates: 44.3% of Black participants and 10.5% of White participants had "limited literacy" (<9th grade reading level, a potential marker of poor education quality), which was associated with a 53% greater hazard of dementia compared with "adequate literacy" (≥ 9th grade reading level) after adjusting for educational attainment. Applying these parameters to a hazard ratio of 1.37 (95%CI: 1.12,1.67) for the risk of dementia comparing Black to White participants, we obtained an adjusted hazard ratio of 1.17 (0.96,1.43), a 54% reduction. DISCUSSION: Present studies are limited in their consideration of education quality. Our work using available measures from the literature suggests that if education quality were equalized across groups by race, without changing disparities in attainment, racial disparities in dementia would be reduced by about half. Future work should seek to consistently incorporate education quality in order to better understand the sources of disparities.

A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021.

Importance: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID. Objective: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery. Design: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study. Results: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms. Conclusions and relevance: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane. Key Points: Question: What are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?Findings: Globally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.Meaning: The substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.

Thrombolysis, time-to-treatment and in-hospital outcomes among young adults with ischaemic stroke in China: findings from a nationwide registry study in China.

BACKGROUND AND PURPOSE: We aimed to determine whether young adults (<50 years) with acute ischaemic stroke (AIS) are more likely to receive intravenous tissue plasminogen activator (IV tPA) and have shorter time to treatment than older patients with stroke. METHODS: We analysed data from the Chinese Stroke Center Alliance registry for patients with AIS hospitalised between August 2015 and July 2019. Patients were classified into two groups according to age: young adults (<50 years of age) and older adults (≥50 years of age). RESULTS: Of 793 175 patients with AIS admitted to 1471 hospitals, 9.1% (71 860) were young adults. Compared with older adults, a higher proportion of young adults received IV tPA among patients without contraindicaitons (7.2% vs 6.1%, adjusted OR (aOR) 1.13, 95% CI 1.10 to 1.17) and among patients without contraindications and with onset-to-door time ≤3.5 hours (23.6% vs 19.3%, aOR 1.20, 95% CI 1.15 to 1.24). We did not observe differences in onset-to-needle time (median hours 2.7 hours) or door-to-needle time (DNT) (median minutes 60 min) between young and older adults. The proportion of DNT ≤30 min, DNT ≤45 min and DNT ≤60 min in young and older IV tPA-treated patients were 16.9% vs 18.8%, 30.2% vs 32.8% and 50.2% vs 54.2%, respectively. Compared with older adults, young adults treated with IV tPA had lower odds of in-hospital mortality (0.5% vs 1.3%, aOR 0.54, 95% CI 0.35 to 0.82) and higher odds of independent ambulation at discharge (61.0% vs 53.6%, aOR 1.15, 95% CI 1.08 to 1.22), and the associations may be partly explained by stroke severity measured by the National Institutes of Health Stroke Scale score. CONCLUSION: Young adults with AIS were more likely to receive IV tPA than older adults, although there was no difference between the two groups in time to treatment. Compared with older adults, young adults may had better in-hospital outcomes.

Assessment of hearing and vision impairment in cohort studies collecting cognitive data in older adults.

INTRODUCTION: There are no standard practices for considering sensory impairment in studies measuring cognitive function among older adults. Exclusion of participants with impairments may inaccurately estimate the prevalence of cognitive impairment and dementia. METHODS: We surveyed prospective cohort studies measuring cognitive function in older adults, determined the proportion that excluded participants based on sensory impairment and the proportion that assessed each type of sensory impairment, and described the methods of sensory assessment. RESULTS: Investigators/staff from 85 (of 192 cohorts) responded; 6 (7%) excluded participants with severe impairment; 80 (94%) measured hearing and/or vision impairment, while 5 (6%) measured neither. Thirty-two (38%) cohorts assessed hearing objectively and 45 (53%) assessed vision objectively. DISCUSSION: Findings indicate variation in methods used to assess sensory impairment, with potential implications for resource allocation. To ensure equitable inclusion of study participants, consensus is needed on best practices standardized protocols for assessment and accommodations of sensory impairment.

Sex differences in vascular risk factors, in-hospital management, and outcomes of patients with acute ischemic stroke in China.

BACKGROUND: Previous assessments of sex differences for patients with acute ischemic stroke were limited in a specific region or population, narrow scope, or small sample size. METHODS: Patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals were analyzed. Absolute standardized differences (ASDs) were used to assess sex differences in vascular risk factors, guideline-recommended in-hospital management measures and outcomes, including stroke severity (National Institutes of Health Stroke Scale≥16), death/discharge against medical advice, major adverse cardiovascular events, pneumonia, and disability (modified Rankin Scale≥3). RESULTS: Of 838,229 patients analyzed, 524351 (62.6%) were men and 313,878 (37.4%) were women. Compared with men, women were older (68.6 vs. 64.7 years), had higher prevalence of hypertension (67.7% vs. 62.4%), diabetes (24.7% vs. 19.5%), and atrial fibrillation (7.1% vs. 4.3%), but lower prevalence of smoking (4.5% vs. 56.6%) and drinking (2.6% vs 35.8%) (ASDs >10%). No sex differences were seen in guideline-directed management measures, indicated by risk-adjusted individual measures and the all-or-null summary measure (34.5% vs 34.9%, ASD = 1.0%). Compared to men, women tended to have strokes that were more severe at presentation (6.5% vs. 4.5%, ASD = 8.8%) and more disabilities at discharge (34.9% vs 30.5%, ASD =9.4%). However, all sex-related differences in outcomes were attenuated to null after risk adjustments (ASDs<2%). CONCLUSIONS: Compared to male patients, female patients had more vascular risk factors and received similar in-hospital care. They had strokes that were more severe at presentation and more disabilities at discharge, both of which may be explained by worse vascular risk profiles.

Racial differences in persistence to secondary prevention medication regimens after ischemic stroke.

BACKGROUND: Prior stroke is one of the biggest risk factors for future stroke events. Effective secondary prevention medication regimens can dramatically reduce recurrent stroke risk. Guidelines recommend the use of antithrombotic, antihypertensive and lipid-lowering medications after stroke. Medication adherence is known to be better in the presence of a caregiver but long-term adherence after stroke is unknown and disparities may persist. METHODS: We examined the effects of race and sex on baseline prescription and maintenance of secondary prevention regimens in the presence of a caregiver using the Caring for Adults Recovering from the Effects of Stroke (CARES) study, an ancillary study of the national REasons for Geographic and Racial Differences in Stroke (REGARDS). RESULTS: Incident ischemic stroke survivors (N = 172; 36% Black) with family caregivers had medications recorded at hospital discharge and on average 9.8 months later during a home visit. At discharge, antithrombotic prescription (95.9%), lipid-lowering medications (78.8%) and antihypertensives (89.9%) were common and there were no race or sex differences in discharge prescription rates. One year later, medication persistence had fallen to 86.6% for antithrombotics (p = 0.002) and 69.8% for lipid lowering (p = 0.008) but increased to 93.0% for antihypertensives (p = 0.30). Blacks were more likely to have discontinued antithrombotics than Whites (18.3% v 7.7%, p = 0.04). No significant differences in persistence were seen with age, sex, income, depression, or cognitive impairment. CONCLUSIONS: Medication persistence was high in this sample, likely due to the presence of a caregiver. In our cohort, despite similar prescription rates at the time of hospital discharge, Black stroke survivors were more than twice as likely to stop antithrombotics than Whites. The effect of changes in patterns of medication usage on health outcomes in Black stroke survivors warrants continued investigation.

Guideline-directed low-density lipoprotein management in high-risk ischemic stroke or transient ischemic attack admissions in China from 2015 to 2019.

BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) is crucial for secondary stroke prevention in stroke patients with preexisting cardiovascular diseases (CVD) or cerebrovascular diseases (CeVD). However, data on attainment of guideline-recommended LDL-C levels are lacking. METHODS: We analyzed data from the Chinese Stroke Center Alliance (CSCA) program for patients with ischemic stroke and transient ischemic attack (TIA) hospitalized between August 2015 and July 2019. Participants were classified into different disease groups according to preexisting CeVD (stroke/TIA) or CVD [coronary heart disease (CHD) or myocardial infarction (MI)]. RESULTS: Of 858,509 patients presenting with an acute stroke/TIA, 251,176 (29.3%) had a preexisting CeVD, 44,158 (5.1%) had preexisting CVD, 33,070 (3.9%) had concomitant preexisting CeVD and CVD, and 530,105 (61.7%) had no documented history of CeVD/CVD. Overall, only 397,596 (46.3%) met the target for LDL-C <2.6 mmol/L, 128,177 (14.9%) for LDL-C <1.8 mmol/L and 55,275 (6.4%) for LDL-C <1.4 mmol/L, and patients with concomitant CeVD and CVD had higher attainment rates than other disease groups (P<0.001). Despite improvements over time in the proportion of patients who attain LDL-C targets (P for trend <0.05), it remains suboptimal. Younger age, women, having a history of hypertension or dyslipidemia, current smoking or drinking, and being admitted to hospitals located in eastern China were associated with lower odds of meeting the LDL-C goals. CONCLUSIONS: Overall attainment of guideline LDL-C targets in a population of stroke/TIA patients is low and indicates the need for better management of dyslipidemia, particularly for high-risk stroke patients with pre-existing CeVD or CVD.

Clinical Characteristics, Management, and In-Hospital Outcomes in Patients With Stroke or Transient Ischemic Attack in China.

Importance: Stroke represents a significant burden on the health care system of China. The Chinese Stroke Center Alliance was launched in 2015 to monitor and improve care quality and outcomes for patients with acute stroke and transient ischemic attack (TIA). Objective: To evaluate the clinical characteristics, management, and in-hospital clinical outcomes and complications among patients with stroke or TIA in China. Design, Setting, and Participants: This quality improvement study assessed stroke or TIA admissions to 1476 participating hospitals in the Chinese Stroke Center Alliance between August 1, 2015, and July 31, 2019. Exposures: Stroke types and calendar year. Main Outcomes and Measures: Eleven guideline-based admission or discharge management measures and 2 summary measures: an all-or-none binary outcome and a composite score (range, 0 [nonadherence] to 1 [perfect adherence]) for adherence to evidence-based stroke and TIA care and in-hospital clinical outcomes, including death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACEs), including ischemic stroke, hemorrhagic stroke, TIA, or myocardial infarction; and in-hospital complications. Results: Of 1 006 798 patients with stroke or TIA (mean [SD] age, 65.7 [12.2] years; 383 500 [38.1%] female), 838 229 (83.3%) had an ischemic stroke, 64 929 (6.4%) had TIA, 85 705 (8.5%) had intracerebral hemorrhage (ICH), and 11 241 (1.1%) had subarachnoid hemorrhage (SAH). Management measures varied by cerebrovascular event type, with the mean (SD) composite score ranging from 0.57 (0.31) in SAH to 0.83 (0.24) in TIA. Poor outcomes and complications were highest among patients with SAH (21.9%; 95% CI, 21.0%-22.8% in-hospital death or DAMA; 9.6%; 95% CI, 9.1%-10.2% MACEs; and 31.4%; 95% CI, 30.6%-32.3% in-hospital complications) and patients with ICH (17.2%; 95% CI, 16.9%-17.5% in-hospital death or DAMA; 9.3%; 95% CI, 9.1%-9.5% MACEs; and 31.3%; 95% CI, 31.0%-31.6% in-hospital complications), followed by patients with ischemic stroke (6.1%; 95% CI, 6.0%-6.1% in-hospital death or DAMA; 6.3%; 95% CI, 6.3%-6.4% MACEs; and 12.8%; 95% CI, 12.7%-12.9% in-hospital complications), and lowest in patients with TIA (5.0%; 95% CI, 4.8%-5.2% in-hospital death or DAMA; 2.4%; 95% CI, 2.3%-2.5% MACEs; and 0.8%; 95% CI, 0.7%-0.8% in-hospital complications). Temporal improvements in management measures were observed from 2015 to 2019, especially in administration of intravenous recombinant tissue plasminogen activator (+60.3% relatively; 95% CI, 52.9%-70.5%), dysphagia screening (+14.7% relatively; 95% CI, 14.0%-15.6%), and use of anticoagulants for atrial fibrillation (+31.4% relatively; 95% CI, 25.7%-37.3%). Temporal improvements in in-hospital death or DAMA (-9.7% relatively; 95% CI, -9.6% to -8.5%) and complications (-27.1% relatively; 95% CI, -28.6% to -25.3) were also observed. Conclusions and Relevance: In this quality improvement study, performance measure adherence and poor outcomes and complications varied by cerebrovascular event type; although there were substantial improvements over time, these results suggest that support for the use of evidence-based practices is needed.

Barriers to medication adherence in a rural-urban dual economy: a multi-stakeholder qualitative study.

BACKGROUND: One of the most cost-effective treatments for secondary prevention of stroke and other non-communicable diseases is a long-term medication regimen. However, the complexities of medication adherence extend far beyond individual behavior change, particularly in low- and middle-income countries. The purpose of this study was to examine stakeholder perspectives on barriers to medication adherence for stroke patients in Beijing, China, identifying opportunities to improve care and policy in resource-constrained settings. METHODS: We conducted a qualitative, phenomenological analysis of data obtained from 36 individuals. Participants were patients; caregivers; healthcare providers; and representatives from industry and government, purposively selected to synthesize multiple perspectives on medication management and adherence for stroke secondary prevention in Beijing, China. Data was analyzed by thematic analysis across iterative coding cycles. RESULTS: Four major themes characterized barriers on medication adherence, across stakeholders and geographies: limitations driven by individual patient knowledge / attitudes; lack of patient-provider interaction time; lack of coordination across the stratified health system; and lack of affordability driven by high overall costs and limited insurance policies. CONCLUSIONS: These barriers to medication management and adherence suggest opportunities for policy reform and local practice changes, particularly for multi-tiered health systems. Findings from this study in Beijing, China could be explored for applicability in other low- and middle-income countries with urban centers serving large geographic regions.

Assessment of Trends in Guideline-Based Oral Anticoagulant Prescription for Patients With Ischemic Stroke and Atrial Fibrillation in China.

Importance: Adherence to oral anticoagulants (OACs) per guideline recommendations is crucial in reducing ischemic stroke and systemic thromboembolism in high-risk patients with ischemic stroke and atrial fibrillation. However, data on OAC use are underreported in China. Objective: To assess adherence to the Chinese Stroke Association or the American Heart Association/American Stroke Association's clinical management guideline-recommended prescription of OACs, the temporal improvement in adherence, and the risk factors associated with OAC prescriptions. Design, Setting, and Participants: This quality improvement study was conducted at 1430 participating hospitals in the Chinese Stroke Center Alliance (CSCA) among patients with ischemic stroke and atrial fibrillation enrolled in the CSCA between August 1, 2015, and July 31, 2019. Exposure: Calendar year. Main Outcomes and Measures: Adherence to the Chinese Stroke Association or the American Heart Association/American Stroke Association's clinical management guideline-recommended prescribing of OACs (warfarin and non-vitamin K OACs, including dabigatran, rivaroxaban, apixaban, and edoxaban) at discharge. Results: Among 35 767 patients (18 785 women [52.5%]; mean [SD] age, 75.5 [9.2] years) with previous atrial fibrillation at admission, the median CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes, and stroke, transient ischemic attack or thromboembolism [2 points]-vascular disease, and sex category [female]) score was 4.0 (interquartile range, 3.0-5.0); 6303 (17.6%) were taking OACs prior to hospitalization for stroke, a rate that increased from 14.3% (20 of 140) in the third quarter of 2015 to 21.1% (118 of 560) in the third quarter of 2019 (P < .001 for trend). Of 49 531 eligible patients (26 028 men [52.5%]; mean [SD] age, 73.4 [10.4] years), 20 390 (41.2%) had an OAC prescription at discharge, an increase from 23.2% (36 of 155) in the third quarter of 2015 to 47.1% (403 of 856) in the third quarter of 2019 (P < .001 for trend). Warfarin was the most commonly prescribed OAC (11 956 [24.2%]) and had the largest temporal increase (from 5.8% [9 of 155] to 20.7% [177 of 856]). Older age (adjusted odds ratio [aOR] per 5 year increase, 0.89;95% CI, 0.89-0.90), lower levels of education (aOR for below elementary school, 0.84; 95% CI, 0.74-0.95 ), lower income (aOR for ≤¥1000 [$154], 0.66; 95% CI, 0.59-0.73), having new rural cooperative medical scheme insurance (aOR, 0.92; 95% CI, 0.87-0.96), prior antiplatelet use (aOR, 0.70; 95% CI, 0.66-0.74), having several cardiovascular comorbid conditions (including stroke or transient ischemic attack [aOR, 0.78; 95% CI, 0.75-0.82], hypertension [aOR, 0.84; 95% CI, 0.80-0.89], diabetes [aOR, 0.91; 95% CI, 0.83-0.99], dyslipidemia [aOR, 0.87; 95% CI, 0.80-0.94], carotid stenosis [aOR, 0.83; 95% CI, 0.69-0.98], and peripheral vascular disease [aOR, 0.80; 95% CI, 0.71-0.90]), and admission to secondary hospitals (aOR, 0.71; 95% CI, 0.68-0.74) or hospitals located in the central region of China (aOR, 0.80; 95% CI, 0.75-0.84) were associated with not being prescribed an OAC at discharge. Conclusions and Relevance: This quality improvement study suggests that, despite significant improvement over time, OAC prescriptions remained low. Efforts to increase OAC prescriptions, especially non-vitamin K OACs, are needed for vulnerable subgroups by age, socioeconomic status, and presence of comorbid conditions.

Secondary prevention medication persistence and prognosis of acute ischaemic stroke or transient ischaemic attack.

INTRODUCTION: The risk of disability and mortality is high among recurrent stroke, which highlights the importance of secondary prevention measures. We aim to evaluate medication persistence for secondary prevention and the prognosis of acute ischaemic stroke or transient ischaemic attack (TIA) in China. METHODS: Patients with acute ischaemic stroke or TIA from the China National Stroke Registry II were divided into 3 groups based on the percentage of persistence in secondary prevention medication classes from discharge to 3 months after onset (level I: persistence=0%, level II: 0%

Change in Life's Simple 7 Measure of Cardiovascular Health After Incident Stroke: The REGARDS Study.

BACKGROUND AND PURPOSE: Life's Simple 7 (LS7) is a metric for cardiovascular health based on the 7 domains of smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose. Because they may be targeted for secondary prevention purposes, we hypothesized that stroke survivors would experience improvement in LS7 score over time compared with people who did not experience a stroke. We addressed this hypothesis in the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) cohort of Black and White adults enrolled between 2003 and 2007. METHODS: Participants who had LS7 data at baseline, were stroke-free at baseline, had a 10-year follow-up visit, and either did not have a stroke or had an ischemic stroke >1 year before follow-up were included (N=7569). Among these participants, 149 (2.0%) had an adjudicated ischemic stroke between the LS7 assessments. LS7 scores were classified as 0 to 2 points for each domain for a maximum score of 14, with higher scores representing better health. Multivariable linear regression was used to test the association of ischemic stroke with change in LS7 score. Covariates included baseline LS7 score, age, race, sex, education, and geographic region. RESULTS: The 149 stroke survivors had an average of 4.9 years (SD=2.5) of follow-up from the stroke event to the second LS7 assessment. After adjusting for covariates, participants who experienced an ischemic stroke showed 0.28 points more decline in total LS7 score (P=0.03) than those who did not experience a stroke. CONCLUSIONS: Stroke survivors did not experience improvements in cardiovascular health due to secondary prevention after ischemic stroke. On the contrary, they experienced significantly greater decline, indicating the need for greater efforts in secondary prevention after a stroke.