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Purpose: Among patients with atrial fibrillation (AF), a nonpharmacologic option (e.g., percutaneous left atrial appendage occlusion [LAAO]) is needed for patients with oral anticoagulant (OAC) contraindications. Among beneficiaries in the Medicare fee‐for‐service coverage 20% sample databases (2015–18) who had AF and an elevated CHA2DS2‐VASc score, we assessed the association between percutaneous LAAO versus OAC use and risk of stroke, hospitalized bleeding, and death. Methods: Patients undergoing percutaneous LAAO were matched to up to five OAC users by sex, age, date of enrollment, index date, CHA2DS2‐VASc score, and HAS‐BLED score. Overall, 17 156 patients with AF (2905 with percutaneous LAAO) were matched (average ± SD 78 ± 6 years, 44% female). Cox proportional hazards model were used. Results: Median follow‐up was 10.3 months. After multivariable adjustments, no significant difference for risk of stroke or death was noted when patients with percutaneous LAAO were compared with OAC users (HRs [95% CIs]: 1.14 [0.86–1.52], 0.98 [0.86–1.10]). There was a 2.94‐fold (95% CI: 2.50–3.45) increased risk for hospitalized bleeding for percutaneous LAAO compared with OAC use. Among patients 65 to <78 years old, those undergoing percutaneous LAAO had higher risk of stroke compared with OAC users. No association was present in those ≥78 years. Conclusion: In this analysis of real‐world AF patients, percutaneous LAAO versus OAC use was associated with similar risk of death, nonsignificantly elevated risk of stroke, and an elevated risk of bleeding in the post‐procedural period. Overall, these results support results of randomized trials that percutaneous LAAO may be an alternative to OAC use for patients with contraindications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

P2Y12 inhibitors (i.e., clopidogrel, prasugrel, or ticagrelor) are effective at reducing adverse cardiovascular outcomes post‐revascularization in coronary artery disease (CAD). However, the choice of a specific P2Y12 inhibitor may vary according to the patient's characteristics, and trends in the use of different P2Y12 inhibitors are not well studied in real‐world settings. The objective of this study is to determine trends in the prescription patterns of P2Y12 inhibitors in patients with CAD. We studied 137,073 patients with CAD cross‐sectionally using the IBM MarketScan database (2013–2018). Patients with CAD prescribed P2Y12 inhibitors within 14 days of index revascularization were included to compare the utilization of P2Y12 inhibitors based on age and clinical characteristics. There were differences in prescription patterns by age. Among patients aged less than or equal to 65 years (N = 92,734), a continuously increased utilization of ticagrelor was observed from 13.7% to 45.6% replacing clopidogrel as the most prescribed medication by 2018. Similarly, ticagrelor was the choice of drug among patients undergoing percutaneous coronary intervention. Among the patients at high bleeding risk, clopidogrel remained the most prescribed medication with use in 50.6% of patients in 2018 in patients aged less than or equal to 65 years. Contrarily, among the older adults with age 65 or above (N = 44,339), although ticagrelor use increased with time, clopidogrel remained the most utilized drug and was used by 66.2% of patients in 2018. Additionally, clopidogrel was the preferred medication among patients with stroke history. With the increasing use of ticagrelor in real‐world practice, further research is needed to observe its impact on cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The fraction of dementia attributable to hypertension might vary depending on the age of the population considered and the age through which dementia occurs. METHODS: In the Atherosclerosis Risk in Communities study, we quantified population attributable fractions (PAF) of dementia by age 80 and 90 from hypertension assessed at ages of 45–54 (n = 7572), 55–64 (n = 12,033), 65–74 (n = 6561), and 75–84 (n = 2086). RESULTS: The PAF for dementia by age 80 from all non‐normal blood pressure at ages 45–54 was 15.3% (95% confidence interval [CI] = 6.9%–22.3%), 19.1% (95% CI = 9.9%–26.9%) at ages 55–64, and 19.9% (95% CI = −4.4%–38.5%) at ages 65–74. The strongest PAFs were from stage 2 hypertension (11.9%–21.3%). For dementia by age 90, PAFs from non‐normal blood pressure up through age 75 were smaller (10.9%–13.8%), and non‐significant by age 75–84. DISCUSSION: Interventions targeting hypertension even in early late life might reduce a sizeable proportion of dementia. Highlights: We estimated prospective population attributable risks of dementia for hypertension.15%–20% of dementia cases by age 80 are from non‐normal blood pressure (BP).Associations between hypertension and dementia persisted through age 75.Midlife to early late‐life BP control might reduce a large proportion of dementia. [ABSTRACT FROM AUTHOR]

Background: Recent evidence indicates that abnormal P‐wave parameters (PWPs)—ECG markers of atrial myopathy—are associated with incident dementia, independent of atrial fibrillation (AF) and clinical ischemic stroke. However, the mechanisms remain unclear and may include subclinical vascular brain injury. Hence, we evaluated the association of abnormal PWPs with brain MRI correlates of vascular brain injury in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC‐NCS). Methods: ARIC‐NCS participants who underwent 3T brain MRI scans in 2011–2013 were included. PWPs were measured from standard 12‐lead ECGs. Brain MRI outcomes included cortical infarcts, lacunar infarcts, cerebral microhemorrhages, brain volumes, and white matter disease (WMD) volume. We used weighted multivariable logistic and linear regression to evaluate the associations of abnormal PWPs with brain MRI outcomes. Results: Among 1715 participants (mean age, 76.1 years; 61% women; 29% Black), 797 (46%) had ≥1 abnormal PWP. After multivariable adjustment, including adjusting for prevalent AF, abnormal P‐wave terminal force in lead V1 (aPTFV1) and prolonged P‐wave duration (PPWD) were associated with increased odds of both cortical (OR 1.41; 95% CI, 1.14 to 1.74 and OR 1.30; 95% CI, 1.04 to 1.63, respectively) and lacunar infarcts (OR 1.36; 95% CI, 1.15 to 1.63 and OR 1.37; 95% CI, 1.15 to 1.65, respectively). Advanced interatrial block (aIAB) was associated with higher odds of subcortical microhemorrhage (OR 2.04; 95% CI, 1.36 to 3.06). Other than a significant association between aPTFV1 with lower parietal lobe volume, there were no other significant associations with brain or WMD volume. Conclusion: In this exploratory analysis of a US community‐based cohort, ECG surrogates of atrial myopathy are associated with a higher prevalence of brain infarcts and microhemorrhage, suggesting subclinical vascular brain injury as a possible mechanism underlying the association of atrial myopathy with dementia. [ABSTRACT FROM AUTHOR]

Background: Strong psychosocial health has been linked to preserved cognition and functional independence in older adults. Associations between late‐life psychosocial health and dementia risk have been established in older adults, but it remains less clear how one's social interactions in mid‐life may relate to dementia risk in late life. We hypothesized that social engagement in mid‐life will be negatively associated with the risk of dementia in late‐life. Method: We included data from 13,216 dementia‐free participants at midlife (mean age: 57.0 years, SD: 5.7 years, 54.9% female, 23.8% Black) from the Atherosclerosis Risk in Communities (ARIC) cohort study. Social support and isolation were assessed via interviewer‐administered questionnaires (visit 2: 1990‐1992). Based upon categorization of both factors, participants were classified as having high, intermediate, or low mid‐life social engagement. Incident dementia cases were identified from visit 2 through December 31, 2019 with ongoing surveillance (e.g., in‐person neurocognitive testing, informant interviews, and hospitalization codes). Primary analyses used Cox proportional hazards regression models and were adjusted for demographics, APOE ε4, occupational/marital status, depressive symptoms, and vascular risk factors measured at visit 2. Secondary analyses examined whether sex and/or race modified the association between mid‐life social engagement and dementia risk with formal tests for interaction. Result: Among 13,261 participants, 2,555 developed dementia (median follow‐up: 23.7 years). Participants with high (hazard ratio (HR): 0.77, 95% CI: 0.68 ‐ 0.86) or intermediate social engagement (HR: 0.84, 95% CI: 0.74 – 0.95) in mid‐life had a lower risk for developing dementia, compared to participants with low social engagement in mid‐life (Figure 1, Table 1). Sex modified this effect (p‐value for interaction = 0.042) whereas race did not. In males, only those with high social engagement in mid‐life had a lower risk of dementia; the association between males with intermediate social engagement in mid‐life and dementia risk was not significant (Table 2). Conclusion: Greater social engagement in mid‐life is associated with a lower risk of dementia. This finding provides further evidence that mid‐life may be a critical time window for dementia prevention. Longitudinal studies evaluating the mechanisms by which psychosocial factors modify the likelihood of incident dementia are needed. [ABSTRACT FROM AUTHOR]

Background: Good sleep is essential for health, yet the role of sleep in dementia risk is incompletely understood. The Sleep and Dementia Consortium (SDC) was established to study associations between polysomnography (PSG)‐derived sleep metrics and the risk of dementia and related cognitive and brain MRI endophenotypes. This study presents the associations of sleep architecture and obstructive sleep apnea (OSA) with cognitive function across participating cohorts. Method: The SDC curates data from five population‐based cohorts with methodologically consistent, overnight, home‐based PSG and neuropsychological assessments over 5 years of follow‐up. Cohorts include the Atherosclerosis Risk in Communities (ARIC) study, Cardiovascular Health Study (CHS), Framingham Heart Study (FHS), Osteoporotic Fractures in Men Study (MrOS), and Study of Osteoporotic Fractures (SOF). Global cognitive composite scores were derived from principal component analysis as the primary outcome. All sleep metrics were harmonized centrally and then distributed to the participating cohorts for cohort‐specific analysis using linear regression; study‐level estimates were pooled in random effects meta‐analyses. Results are adjusted for demographic variables, the time interval between the PSG and neuropsychological assessment (0‐5 years), body mass index, antidepressant use, and sedative medication use. Result: The mean age of the cohorts ranged from 58 to 89 years (Figure 1) with a pooled sample of 5,946 participants. As shown in Figure 2, across cohorts, higher REM sleep percentage (pooled β±SE = 0.49±0.18 per % increase; p = 0.008) and Sleep Maintenance Efficiency (pooled β±SE = 0.08±0.03 per % increase; p = 0.01) were associated with better global cognition whereas OSA (Apnea‐hypopnea index [AHI] ≥ 5) was associated with worse global cognition (pooled β±SE = ‐0.06±0.02 vs. AHI<5; p = 0.03). Differences in N3 sleep were not associated with cognition. Conclusion: Better sleep consolidation and higher REM sleep percentage were associated with better cognition whereas OSA was associated with worse cognition over 5‐years follow‐up. The role of interventions to improve sleep for maintaining cognitive function and potentially reduce dementia risk requires investigation. [ABSTRACT FROM AUTHOR]

Background: Although amyloid deposition in the brain is often associated with subsequent dementia risk, not everyone with brain amyloid will develop dementia. This discrepancy illustrates the potential importance that risk factors and lived experiences may have in modifying this association. Compared to participants with low social engagement (SE) in mid‐life, we hypothesized that participants with high mid‐life SE will show a weaker association between amyloid burden and incident dementia. Method: We included data from 310 non‐demented participants of the Atherosclerosis Risk in Communities (ARIC)‐PET study. Social support and isolation were assessed via interviewer‐administered questionnaires (Visit 2; 1990 – 1992). Based upon categorization of both factors, participants were classified as having high, intermediate, or low mid‐life SE (Table 1). Brain amyloid was evaluated with florbetapir PET (Visit 5; 2011‐2014). Elevated amyloid burden was defined as standardized uptake value ratio (SUVR) >1.2 in the global cortex. Incident dementia cases were identified from visit 5 through 2019 through ongoing surveillance utilizing in‐person neurocognitive testing, informant interviews, and hospitalization codes. Relative contributions of mid‐life SE and elevated florbetapir SUVR to incident dementia, independently and with multiplicative interaction terms, were evaluated with Cox regression models, adjusted for demographics, APOEε4 and vascular risk factors Result: Among 310 participants, 48 developed dementia (median follow‐up: 4.7 years). Mid‐life SE and elevated SUVR each independently predicted dementia risk but did not interact on a multiplicative scale. Participants with high or intermediate mid‐life SE, relative to low mid‐life SE, were less likely to develop dementia (Table 2). Although the interaction between mid‐life SE and elevated SUVR was not significant, stratified models suggested a stronger association between amyloid burden and dementia in participants with high mid‐life SE (Table 3). Conclusion: Greater mid‐life SE was associated with lower odds of developing dementia, independent of elevated SUVR. Although protective, there was no strong evidence for effect modification of mid‐life SE on the association between amyloid and dementia risk. Future longitudinal studies evaluating the potential influence of social factors measured throughout the life course are needed to inform our understanding as to what factors may preserve cognition in the presence of elevated brain pathology. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated whether better cardiovascular health at midlife and improvement of cardiovascular health within midlife were associated with dementia risk. Methods: Two longitudinal population‐based studies were used: Atherosclerosis Risk in Communities (ARIC) (n = 11,460/visits at ages 54 and 60), and Age, Gene/Environment Susceptibility (AGES)‐Reykjavik (n = 3907/visit at age 51). A cardiovascular health score (range 0–12/0–14, depending on diet availability) including six/seven items was calculated at each visit, with weight assigned to each item as poor (0), intermediate (1), or ideal (2). Cardiovascular health was defined as low (score 0–4/0–5), intermediate (5–7/6–9), or high (8–12/10–14). Incident dementia was ascertained through linkage to health records and with neuropsychological examinations. Results: Midlife high compared to low cardiovascular health (hazard ratios [HRs]: for ARIC: 0.60 [95% confidence interval: 0.52, 0.69]); for AGES‐Reykjavik: 0.83 [0.66, 0.99] and improvement of cardiovascular health score within midlife (HR per one‐point increase: ARIC: 0.94 [0.92, 0.96]) were associated with lower dementia risk. Discussion: Better cardiovascular health at midlife and improvement of cardiovascular health within midlife are associated with lower dementia risk. Highlights: Cardiovascular health and dementia were studied in two large cohort studies.Better cardiovascular health at midlife relates to lower dementia risk.Improvement of cardiovascular health within midlife relates to lower dementia risk.Promotion of cardiovascular health at midlife can help to reduce dementia risk. [ABSTRACT FROM AUTHOR]

Comparative effectiveness evaluation of newer P2Y12 inhibitors (prasugrel and ticagrelor) compared with clopidogrel after acute coronary syndrome (ACS) is limited in real‐world US populations. The objective of this study was to evaluate cardiovascular events based on ticagrelor, prasugrel, and clopidogrel use in a real‐world patient setting. This retrospective cohort study used the IBM MarketScan database (January 1, 2013, to December 31, 2018) to create three propensity score‐matched pairs: ticagrelor vs. clopidogrel (N = 21,719), prasugrel vs. clopidogrel (N = 11,513), and prasugrel vs. ticagrelor (N = 11,065). The primary outcome was a composite of myocardial ischemia, unstable angina, stroke, and heart failure hospitalization. These groups were compared in a time‐to‐event analysis for the primary outcome at 30, 90, and 180 days following P2Y12 inhibitors initiation after percutaneous coronary intervention. Compared with clopidogrel, ticagrelor use suggested a 10% reduction in the primary outcome at 90 days (hazard ratio (HR): 0.90, 95% confidence interval (CI): 0.82–0.99). There were no differences for all other matched pairs or follow‐up combinations. In the subgroup analysis of females, the results suggested a risk reduction of 27% for prasugrel at 30 days (HR: 0.73, 95% CI: 0.53–1.00) and 17% for ticagrelor at 90 days (HR: 0.83, 95% CI: 0.70–0.98) when compared with clopidogrel. Among patients treated with bare‐metal stents, the results suggested that prasugrel vs. ticagrelor was associated with a 55% and 33% reduced risk for the primary outcome at 30 days and 180 days, respectively. With limited evidence in the United States comparing these drugs, this study helps inform clinicians when choosing P2Y12 inhibitors after ACS. [ABSTRACT FROM AUTHOR]

In closely monitored randomized controlled trials (RCTs), newer P2Y12 agents (ticagrelor and prasugrel) reduced cardiovascular outcomes compared with clopidogrel following percutaneous coronary intervention (PCI) in acute coronary syndrome. However, these RCTs indicated a higher bleeding risk with these newer agents. This study evaluated the comparative safety of each P2Y12 inhibitor on hospitalizations due to major bleeding in a real‐world population. This retrospective, propensity score‐matched (PSM) cohort study utilized the IBM MarketScan database over 6 years (2013–2018) to identify incident users of P2Y12 inhibitors with age ≥18 years. The primary safety outcome was hospitalization due to any major bleeding event including gastrointestinal, intracranial, and other serious forms of bleeding. In pairwise comparisons using Cox‐proportional hazards models, ticagrelor, prasugrel, and clopidogrel users were compared for the primary safety outcome at 30, 90, and 180 days following the first prescription of P2Y12 inhibitor after PCI. There were 21,719 (ticagrelor vs. clopidogrel), 11,513 (prasugrel vs. clopidogrel), and 11,065 (prasugrel vs. ticagrelor) PSM pairs. Overall, the risk of major bleeding was similar for all P2Y12 inhibitors. Hospitalization for major bleeding was generally lower among ticagrelor users vs. clopidogrel and higher among prasugrel users compared with clopidogrel. Importantly, a 66% higher risk of major bleeding at 90 days is suggested with prasugrel compared with clopidogrel (hazard ratio 1.66; 95% confidence interval, 1.11–2.48). This study indicated a higher short‐term bleeding risk with prasugrel compared with clopidogrel, which concurs with the results of RCTs. [ABSTRACT FROM AUTHOR]

Aim: We investigate if periodontal disease is prospectively associated with cerebrovascular and neurodegenerative markers of dementia and Alzheimer's pathology. Materials and Methods: N = 1306 participants (Visit 5 mean age = 76.5 [standard deviation = 5.4] years) in the Atherosclerosis Risk in Communities study with completed dental exams at Visit 4 underwent brain magnetic resonance imaging scans at Visit 5 while N = 248 underwent positron emission tomography scans. Participants were classified as edentulous or, among the dentate, by the modified Periodontal Profile Class. Brain volumes were regressed on periodontal status in linear regressions. Cerebrovascular measures and β‐amyloid positivity were regressed on periodontal status in logistic regressions. Results: Periodontal disease was not associated with brain volumes, microhaemorrhages, or elevated β‐amyloid. Compared with periodontally healthy individuals, odds ratios [95% confidence interval] for all‐type infarcts were 0.37 [0.20, 0.65] for severe tooth loss and 0.56 [0.31, 0.99] for edentulous participants. Conclusions: Within the limitations of this study, periodontal disease was not associated with altered brain volumes, microhaemorrhages, or β‐amyloid positivity. Tooth loss was associated with lower odds of cerebral infarcts. [ABSTRACT FROM AUTHOR]

Background: Early life factors, such as birth weight (BW), may have long‐term health consequences, but the importance of these factors in dementia risk is poorly understood. Our objective was to prospectively examine the association of BW with dementia incidence over mid‐ to late‐adulthood in the ARIC study. We hypothesized that participants who report lower BW experience more incident dementia than participants who report normal BW, and this association may differ by race. Method: 10,789 participants who were dementia‐free at ARIC baseline (Visit 1: 1987‐1989; ages 45‐64) and followed through 2019 were included. Participants were asked their BW through standard interviews at Visit 4 (1996‐1998), but if unable to recall, they selected their BW category: low (<5.5 lbs.), medium (normal) (5.5‐9.0 lbs.), or high (>9.0 lbs.), and to identify if they were premature (yes/no). Adjudicated dementia cases from baseline through 2019 were classified using in‐person cognitive evaluations, informant interviews, and phone assessments as well as hospitalization codes and death certificate codes. The associations between having high or low (vs medium) BW and dementia, or premature birth status and dementia were investigated using Cox proportional hazards models, with testing for interaction by race. Result: Our overall population was 54 yo at baseline, 56% female, and 20% Black; 2,255 dementia cases were identified over a median of 28.2 years. Participants who reported a low BW had 1.2 times (95% CI 1.02, 1.41) increased risk of incident dementia compared to those with medium BW in demographic‐ and APOE‐adjusted models (Table 1). This association was no longer significant when the model additionally adjusted for vascular risk factors. The risk for dementia was not increased among participants who reported having been born premature (vs not premature). When stratified by race, the risk of incident dementia was elevated in Black participants reporting high (vs medium) BW, but not in White participants reporting high BW (p‐interaction = 0.006) (Table 2). Conclusion: In this cohort, low BW was associated with risk of dementia in minimally adjusted models. The association was attenuated after accounting for vascular risk factors. High BW was associated with risk of dementia in Black participants only. [ABSTRACT FROM AUTHOR]

Background: Adequate sleep is necessary to maintain brain health, with sleep disturbances associated with higher Alzheimer's disease (AD) risk. Diffusion‐weighted imaging (DWI) metrics are increasingly recognized as useful neuroimaging biomarkers to detect AD‐related white matter degeneration. We assessed the relationship between sleep patterns and prospective DWI metrics in the Sleep and Dementia Consortium (SDC). The SDC studies associations between polysomnography (PSG)‐derived sleep with dementia risk and cognitive and MRI endophenotypes. Method: The SDC includes five community‐based cohorts, two of which have DWI acquisitions: The Framingham Heart Study (FHS) and the Atherosclerosis Risk in Communities study (ARIC). Dementia‐free participants who underwent both PSG and DWI‐MRI were selected, including 354 FHS participants (56.6±7.1y, 57%W), and 184 ARIC participants (61.6±5.0y, 52%W). The MRI session was approximately 15 years after the PSG on average (FHS:17.0±1.3y; ARIC:15.8±0.8y). Fractional anisotropy (FA) and mean diffusivity (MD) were considered for both cohorts, in addition to free‐water (FW) in the FHS. Sleep metrics were harmonized centrally, distributed for cohort‐specific linear regressions, and study‐level estimates were pooled in random effects meta‐analyses. Analyses were adjusted for demographics, obesity, time between PSG and MRI, antidepressants and sedative medication usage. An interaction term by APOE4 allele carrier status in regression models was used to test its moderating effect. Result: In the FHS, sleep fragmentation was associated with DWI measures in the expected direction: Higher Wake After Sleep Onset and lower Sleep Maintenance Efficiency were associated with lower FA (β±SE = ‐0.17±0.09,p = 0.04; β±SE = 0.23±0.10,p = 0.03), higher MD (β±SE = 0.15±0.07,p = 0.04; β±SE = ‐0.20±0.09,p = 0.03), and higher FW (β±SE = 0.17±0.07,p = 0.02; β±SE = ‐0.22±0.08,p = 0.008). Meta‐analysis of FHS and ARIC revealed significant pooled effects between lower Sleep Maintenance Efficiency and lower FA (β±SE = 0.17±0.08,p = 0.04). In the FHS, APOE4 allele significantly moderated the association between REM sleep proportion with FA and MD, where lower REM sleep percentage was associated with higher MD (β±SE = ‐4.89±1.95,p = 0.02) and lower FA (β±SE = 4.93±2.26,p = 0.03) in APOE4 carriers only. Conclusion: In the SDC, sleep fragmentation was associated with MRI markers of poorer white matter integrity 15 years later. Less REM sleep was associated with poorer white matter integrity in APOE4 allele carriers only, suggesting that disrupted sleep architecture may contribute and interact with neurodegenerative processes to affect brain integrity. [ABSTRACT FROM AUTHOR]

Background: Biological aging state can be quantified by composite metrics called aging clocks using proteomics. Proteomic aging clocks (PACs) are accurate, easily measured, and are associated with age‐related diseases including Alzheimer's Disease and Related Dementias. We aim to investigate whether an accelerated biological aging (a discrepancy between chronological age and PAC) is associated with subclinical cerebrovascular structural changes. Method: 1494 participants from the Atherosclerosis Risk in Communities (ARIC) Study with proteomics and 3T brain MRI data at ARIC visit 5 in 2011‐13 (mean age 76, 59% female, 25% Black) were included. Nearly 5000 plasma proteins were measured using the SomaScan assay. PAC was developed using elastic net regression model and was internally validated. Age acceleration was calculated as residuals after regressing PAC on chronological age (positive value indicates biological age is higher than the person's chronological age). Linear and logistic regression models were used to assess the associations of age acceleration with white matter hyperintensity volume (in cm3, log2 transformed, median [IQR]: 11[6‐20]) and the presence of: subcortical (n = 281), lacunar (n = 263), and cortical infarcts (n = 150), and microbleeds (n = 355). Result: Accelerated age (median [IQR]:‐0.04[‐1.4,1.3]; correlation with chronological age = 0) was associated with MRI markers of cerebrovascular disease after adjusting for demographic, cardiovascular risk factors, education, and kidney function. Every five years higher age acceleration was associated with larger white matter hyperintensity volume (Difference:0.34[95%CI 0.19,0.49]), higher odds of lacunar (OR:1.61[1.13,2.30]), subcortical (OR:1.63[1.15, 2.32]), and cortical infarcts (OR:1.72[1.11,2.67]). There was no association with presence of microbleeds (OR:1.25[0.91,1.73]) (Figure). Findings were consistent after excluding participants with clinical stroke and there was no difference between APOEe4+ and APOEe4‐ participants. Conclusion: Higher accelerated age is cross‐sectionally associated with a greater prevalence of MRI markers of cerebrovascular disease. Understanding this relation has potential to help with risk stratification and personalized prevention and treatment strategies to promote brain health. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess the association between migraine headache and incident dementia. Background: Migraine is a risk factor for white matter hyperintensities and ischemic stroke, which are both associated with increased risk of dementia. However, it is unknown whether migraine is independently associated with dementia. Methods: History of migraine was ascertained via questionnaire. Adjudicated cases of dementia were identified using cognitive tests, neuropsychological exams, and clinician review of suspected cases. Incident dementia was identified using adjudicated cases, follow‐up calls, and surveillance of hospital and death codes. We assessed hazards of incident dementia by migraine status. Sex differences were also examined and stratified results were presented. Results: Analysis included 12,495 White and African American participants ages 51‐70 with a median follow‐up time of 21 years. Prevalence of dementia was 18.5% (1821/9955) among those with no migraine history, 15.8% (196/1243) among those with severe non‐migraine heading, and 16.7% (233/1397) among migraineurs. There was no association between migraine and incident dementia [hazard ratio: 1.04 (0.91, 1.20)]. There was also no statistically significant interaction between sex and migraine status on risk of dementia. Conclusion: Despite evidence of brain abnormalities in migraineurs, there was no association between migraine and incident dementia in this prospective cohort. [ABSTRACT FROM AUTHOR]

Background: Adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations is associated with colorectal cancer (CRC) risk in whites, but only 1 previous study has reported on this link in African Americans. This study assessed the association between the 2018 WCRF/AICR guidelines and CRC incidence in African Americans (26.5%) and whites (73.5%) in the Atherosclerosis Risk in Communities prospective cohort (n = 13,822).Methods: A total of 368 incident CRC cases (268 among whites and 100 among African Americans) were identified between the baseline (1987) and 2012. A baseline adherence score was created for 7 WCRF/AICR guidelines (each contributing 0, 0.5, or 1 point to the score, with higher scores corresponding to greater adherence). Adherence scores were also categorized as tertiles (0.0-3.0, 3.5-4.0, and 4.5-7.0). Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the total cohort and with stratification by race.Results: After adjustments for age, sex, race, center, smoking, education, intake of aspirin, calcium, total calories, diabetes status, and, in women, hormone replacement therapy, greater adherence was associated with decreased CRC risk. The HRs per 1-unit increment in score were 0.88 (95% CI, 0.80-0.97) for the whole cohort, 0.89 (95% CI, 0.73-1.09) for African Americans, and 0.88 (95% CI, 0.77-0.99) for whites. Similar associations between higher adherence scores and decreased cancer risk were observed for men and women and for colon cancer but not for rectal cancer.Conclusions: Greater adherence to the cancer prevention recommendations appears to be associated with decreased CRC risk for both African Americans and whites. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies on a potential association between endodontic infection (EI) and cardiovascular disease (CVD) produced mixed results. Endodontic treatment (ET) may also be linked to cardiovascular risk, as a marker for prior chronic dental infection and subclinical EI in other teeth. We tested the hypothesis that ET is associated with elevated risk of coronary heart disease (CHD), ischemic stroke (IS), heart failure (HF), or venous thromboembolism (VTE).Methods: ARIC participants who completed the dental ancillary study exam 4 (1996-1998; n = 6,638) were included in the analyses. Participants were followed through 2013 for CHD, stroke, and HF and 2011 for VTE. Cox-proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for CHD, IS, HF, and VTE across ET classifications adjusting for age, sex, race/center, education, income, smoking, alcohol consumption, BMI, statin use, family history of CHD, physical activity, diet quality, insurance status, last dental visit, dental visit frequency, having a current dentist, and tooth loss due to gum disease.Results: Among participants, 21.0% reported a single ET, while 28.5% reported multiple ETs. Over a median of 15.8 years of follow-up, there were 506 incident CHD events, 311 IS events, 739 HF events, and 219 VTE events. There were no significant associations between self-reported history of ET and any of our outcomes (HR (95%CI): CHD = 1.16 (0.87,1.44), IS = 0.77 (0.55,1.09), HF = 1.00 (0.81,1.24), VTE = 0.98 (0.67,1.43)) after adjustment.Conclusions: Our results do not support an independent association between ET and development of CHD, IS, HF, or VTE. [ABSTRACT FROM AUTHOR]

Summary: Understanding of the comparative bleeding risks of oral anticoagulant (OAC) therapies for the primary treatment of venous thromboembolism (VTE) is limited. Therefore, among anticoagulant‐naïve VTE patients, we conducted comparisons of apixaban, rivaroxaban and warfarin on the rate of hospitalised bleeding within 180 days of OAC initation. MarketScan databases for the time‐period from 2011 to 2016 were used and, for each OAC comparison, new users were matched with up to five initiators of a different OAC. The final analysis included 83 985 VTE patients, who experienced 1944 hospitalised bleeding events. In multivariable‐adjusted Cox regression models, rate of hospitalised bleeding was lower among new users of apixaban when compared to new users of rivaroxaban [hazard ratio (95% confidence interval) 0·58 (0·41–0·80)] or warfarin [0·68 (0·50–0·92)]. Overall, the hospitalised bleeding rate was similar when comparing new users of rivaroxaban to new users of warfarin [0·98 (0·68–1·11)], though there was some suggestion that rivaroxaban was associated with lower bleeding risk among younger individuals. Findings from this large real‐world population concur with results from the randomised trial which found lower bleeding risk with apixaban versus warfarin and, for the first time, reveal a lower risk of bleeding in a comparison of apixaban versus rivaroxaban. [ABSTRACT FROM AUTHOR]

Aim: Periodontal disease is a cardiovascular disease (CVD) risk factor but few studies have considered the relationship between periodontal disease and venous thromboembolism (VTE). We hypothesized that periodontal disease is independently associated with increased risk of incident VTE. Materials and methods: We used data from 8,092 participants of the Atherosclerosis Risk in Communities (ARIC) study to examine periodontal disease in 1996–1998 and incident VTE through 2011. Periodontal disease was determined using self‐reported tooth loss due to gum disease and dental examinations. Cox proportional hazards regression models were used to estimate hazard ratios for VTE and 95% confidence intervals adjusted for relevant confounders. Results and conclusions: Participants were on average 62.7 years old at baseline and 13.9% self‐reported tooth loss from gum disease. Over a mean of 12.9 years of follow‐up, there were 313 incident VTE events. Self‐reported tooth loss due to gum disease was associated with 30% higher VTE risk (HR = 1.29 (0.96, 1.73) after adjusting demographic factors, SES, periodontal risk factors, oral hygiene, and access to dental care variables. No statistically significant associations between clinical measures of periodontitis and VTE were observed after adjustment. Further research is needed to elucidate whether a relationship between periodontal disease and VTE exists. [ABSTRACT FROM AUTHOR]

Introduction: This study tested the hypotheses that late‐midlife obstructive sleep apnea (OSA) and short and long sleep duration are associated with dementia over 15 years of follow‐up. Methods: A total of 1667 Atherosclerosis Risk in Communities Study participants underwent in‐home polysomnography (1996–1998) and were followed for dementia. Dementia was defined by (1) hospitalization diagnosis codes (1996–2012) and (2) a comprehensive neurocognitive examination (2011–2013) with adjudication. Results: OSA and sleep duration were not associated with risk of incident dementia. When using adjudicated outcomes, severe OSA (≥30 vs. <5 apnea‐hypopnea events/hour) was associated with higher risk of all‐cause dementia (risk ratio [95% confidence interval], 2.35 [1.06–5.18]) and Alzheimer's disease dementia (1.66 [1.03–2.68]); associations were attenuated with cardiovascular risk factor adjustment. Sleeping <7 versus 8 to ≤9 hours was associated with higher risk of all‐cause dementia (2.00 [1.03–3.86]). Discussion: When adjudicated outcome definitions were used, late‐midlife OSA and short sleep duration were associated with all‐cause and Alzheimer's disease dementia in later life. [ABSTRACT FROM AUTHOR]

Objectives To examine the association between midlife cardiovascular health and physical performance 25 years later. Design Cohort study (Atherosclerosis Risk in Communities Study); multinomial logistic and logistic regression adjusted for demographic characteristics and clinical measures. Setting Four U.S. communities: Forsyth County, North Carolina; Washington County, Maryland; Minneapolis, Minnesota; and Jackson, Mississippi. Participants: Individuals aged 54.2 ± 5.8 at baseline (N = 15,744; 55% female, 27% black). Measurements Cardiovascular health was measured at baseline using the American Heart Association's Life's Simple 7 ( LS7) score (0-14) and LS7 component categories (poor, intermediate, ideal) for each risk factor. The Short Physical Performance Battery ( SPPB) was used to quantify physical function as ordinal (0-12) and categorical (low (0-6), fair (7-9), good (10-12) outcomes. Results Mean baseline LS7 score was 7.9 ± 2.4; 6,144 (39%) individuals returned 25 years later for the fifth ARIC examination, at which point the SPPB was administered. Of 5,916 individuals who completed the SPPB, 3,288 (50%) had good physical performance. Each 1-unit increase in LS7 score was associated with a 17% higher SPPB score (rate ratio ( RR) = 1.17, 95% confidence interval ( CI) = 1.15-1.19) and a 29% greater chance of having a late-life SPPB score of 10 or greater compared to SPPB score of less than 10 ( RR = 1.29, 95% CI = 1.25-1.34). Ideal baseline glucose ( RR = 2.53, 95% CI = 2.24-2.87), smoking ( RR = 1.97, 95% CI = 1.81-2.15), blood pressure ( RR = 1.70, 95% CI = 1.54-1.88), body mass index ( RR = 1.51, 95% CI = 1.37-1.66), and physical activity ( RR = 1.31, 95% CI = 1.20-1.43) had the strongest associations with late-life SPPB score, adjusting for other LS7 components. Conclusion Better cardiovascular health during midlife may lead better physical functioning in older age. [ABSTRACT FROM AUTHOR]