Burden Of Vascular Risk Factors Research Articles

Beat-to-beat blood pressure variability, hippocampal atrophy, and memory impairment in older adults.

Visit-to-visit blood pressure variability (BPV) predicts age-related hippocampal atrophy, neurodegeneration, and memory decline in older adults. Beat-to-beat BPV may represent a more reliable and efficient tool for prospective risk assessment, but it is unknown whether beat-to-beat BPV is similarly associated with hippocampal neurodegeneration, or with plasma markers of neuroaxonal/neuroglial injury. Independently living older adults without a history of dementia, stroke, or other major neurological disorders were recruited from the community (N = 104; age = 69.5 ± 6.7 (range 55-89); 63% female). Participants underwent continuous blood pressure monitoring, brain MRI, venipuncture, and cognitive testing over two visits. Hippocampal volumes, plasma neurofilament light, and glial fibrillary acidic protein levels were assessed. Beat-to-beat BPV was quantified as systolic blood pressure average real variability during 7-min of supine continuous blood pressure monitoring. The cross-sectional relationship between beat-to-beat BPV and hippocampal volumes, cognitive domain measures, and plasma biomarkers was assessed using multiple linear regression with adjustment for demographic covariates, vascular risk factors, and average systolic blood pressure. Elevated beat-to-beat BPV was associated with decreased left hippocampal volume (P = .008), increased plasma concentration of glial fibrillary acidic protein (P = .006), and decreased memory composite score (P = .02), independent of age, sex, average systolic blood pressure, total intracranial volume, and vascular risk factor burden. In summary,beat-to-beat BPV is independently associated with decreased left hippocampal volume, increased neuroglial injury, and worse memory ability. Findings are consistent with prior studies examining visit-to-visit BPV and suggest beat-to-beat BPV may be a useful marker of hemodynamic brain injury in older adults.

Development and validation of a SCORing systEm for pre-thrombectomy diagnosis of IntraCranial Atherosclerotic Disease (Score-ICAD)

BackgroundEarly identification of intracranial atherosclerotic disease (ICAD) may impact the management of patients undergoing mechanical thrombectomy (MT). We sought to develop and validate a scoring system for pre-thrombectomy diagnosis of...

Abstract P246: Geographical Mapping and Cluster Analysis of Ischemic Stroke in Kentucky

Background: Stroke death is the third leading cause of death in the United States, the sixth leading cause of death in Kentucky (KY), and ischemic stroke (IS) is the most prevalent type in adults (~85%). Small area estimates of stroke incidence can help identify local interventions to lower the burden of vascular risk factors and risk of recurrent IS in these areas. Therefore, the goals of this study are to calculate small area IS incidence rates, examine clusters, and understand the distribution of IS in KY. Methods: Data was obtained from the Kentucky Hospital Inpatient Discharge and Outpatient Services Databases (HIDOSD) from 2012 to 2021; and the Kentucky Cabinet for Health and Family Services. HIDOSD represents KY emergency department discharges, inpatient data, and ambulatory facility services. We linked 5-digit Zip codes to (n=759) zip code tabulation areas (ZCTA) available from the US Census Bureau. The annualized IS rate per 100,000 was calculated by dividing the mean number of IS hospitalizations from 2012 to 2021 by the ZCTA 2020 population. We categorized IS rates by quartiles and calculated box plots in descriptive analyses. We tested for significant spatial clusters using the Local Moran’s I with Empirical Bayes rate smoothing in GeoDa. Results: From 2012-2021, 90,840 IS hospitalizations were reported in KY. The median IS rate was 226.5 per 100,000. The median rate in the highest quartile was 290.8 (IQR 171.7 - 290.8) vs 171.7 (IQR 171.7 - 290.8) in the lowest quartile. An area of high IS rate clusters (n=20) was identified in southeastern KY with lower clusters dispersed throughout the state. Figure. Conclusions: This 10-year analysis of IS hospitalizations across KY identified areas of potential intervention. Future efforts are needed to identify the social and medical contributors driving burden of IS in these areas and to design interventions targeted to improve health outcomes.

Cross-sectional associations between neighborhood characteristics, cognition and dementia risk factor burden in middle-aged and older Australians

Dementia disproportionately affects individuals from disadvantaged backgrounds, including those living in areas of lower neighborhood-level socioeconomic status. It is important to understand whether there are specific neighborhood characteristics associated with dementia risk factors and cognition which may inform dementia risk reduction interventions. We sought to examine whether greenspace, walkability, and crime associated with the cumulative burden of modifiable dementia risk factors and cognition. This was a cross-sectional analysis of 2016–2020 data from the Healthy Brain Project, a population-based cohort of community-dwelling individuals across Australia. Participants were aged 40–70 and free of dementia. Measures included greenspace (greenspace % in the local area, and distance to greenspace, n = 2,181); and intersection density (n = 1,159), and crime (rate of recorded offences; n = 1,159). Outcomes included a modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score to index the burden of modifiable vascular dementia risk factors; and composite scores of both memory and attention, derived from the Cogstate Brief Battery. Linear regressions adjusted for age, sex, education, and personal socio-economic status, demonstrated distance to greenspace (b ± SE per 2-fold increase = 0.09 ± 0.03, p =.005) and crime rate (b ± SE per 2-fold increase = 0.07 ± 0.03, p =.018) were associated with higher modified CAIDE. Higher crime was associated with lower memory performance (b ± SE = -0.03 ± 0.01, p =.018). The association between distance to greenspace and modified CAIDE was only present in low-moderate socioeconomic status neighborhoods (p interaction = 0.004). Dementia prevention programs that address modifiable risk factors in midlife should consider the possible role of neighborhood characteristics.

Trends in American Indian/Alaskan native self-reported stroke prevalence and associated modifiable risk factors in the United States from 2011-2021

BackgroundStroke prevalence varies by race/ethnicity, as do the risk factors that elevate the risk of stroke. Prior analyses have suggested that American Indian/Alaskan Natives (AI/AN) have higher rates of stroke and vascular risk factors. MethodsWe included biyearly data from the 2011-2021 Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults (age ≥18) in the United States. We describe survey-weighted prevalence of stroke per self-report by race and ethnicity. In patients with self-reported stroke (SRS), we also describe the prevalence of modifiable vascular risk factors. ResultsThe weighted number of U.S. participants represented in BRFSS surveys increased from 237,486,646 in 2011 to 245,350,089 in 2021. SRS prevalence increased from 2.9% in 2011 to 3.3% in 2021 (p<0.001). Amongst all race/ethnicity groups, the prevalence of stroke was highest in AI/AN at 5.4% and 5.6% in 2011 and 2021, compared to 3.0% and 3.4% for White adults (p<0.001). AI/AN with SRS were also the most likely to have four or more vascular risk factors in both 2011 and 2021 at 23.9% and 26.4% compared to 18.2% and 19.6% in White adults (p<0.001). ConclusionFrom 2011-2021 in the United States, AI/AN consistently had the highest prevalence of self-reported stroke and highest overall burden of modifiable vascular risk factors. This persistent health disparity leaves AI/AN more susceptible to both incident and recurrent stroke.

Abstract 96: Temporal Trends in Vascular Risk Factor Burden Among Young Adults With Ischemic Stroke: The Florida Stroke Registry

Introduction: While ischemic stroke (IS) in the young (18-55) is thought to have different etiologies than in older patients, a rise in vascular risk factors (VRFs) among young adults may translate to an IS risk profile similar to the older population. We aimed to examine the prevalence of VRFs and temporal trends in VRF burden among young patients presenting with IS. Methods: Data was prospectively collected by Get With the Guidelines-Stroke® hospitals participating in the Florida Stroke Registry between January 2010 and December 2022. Patients aged 18-55 with a diagnosis of IS were included and separated into two age groups: 18-35 and 36-55. VRFs included hypertension, dyslipidemia, obesity, smoking, atrial fibrillation, coronary artery disease, heart failure, diabetes, and sleep apnea. Multimorbidity was defined as having ≥4 VRFs. Results: 47,792 patients with IS were included (43% female, median age 49, 51% white), comprising 4,275 patients aged 18-35 (8.9%) and 43,517 aged 36-55 (91.1%). The prevalence of each VRF was higher among patients aged 36-55 vs 18-35 (all p values &lt;0.001), and only 15.3% of patients aged 36-55 and 40.0% of patients aged 18-35 had 0 VRFs. African American patients with IS had a significantly higher prevalence of multimorbidity than white or non-white Hispanic patients; specifically in those aged 18-35 (6.1% vs 3.5% vs 3.5%, p &lt;0.001), while those aged 36-55 demonstrated a smaller difference (17.6% vs 17.2% vs 15.4% p &lt;0.001).VRF burden worsened across the study period, with an increase in multimorbidity from 11.2% to 21.7% in patients 36-55 (p&lt;0.0001) and from 1.3% to 6.6% in patients 18-35 (p= 0.0006). Conclusions: Increasingly, young stroke patients have traditional VRFs. The prevalence of multimorbidity disproportionately affects African American patients and has significantly increased over the past 12 years. Efforts targeting VRFs reduction must start as early as possible in light of the rise in VRF burden amongst young IS patients.

Abstract 87: Predictive Scoring System for Pre-Thrombectomy Diagnosis of Intracranial Atherosclerotic Disease LVOS

Introduction: Early identification of intracranial atherosclerotic disease (ICAD) underlying large vessel occlusion strokes (LVOS) may allow for mechanical thrombectomy (MT) optimization. We sought to create a pre-procedural scoring system to predict ICAD. Methods: Retrospective analysis of prospectively collected MT databases from 2 comprehensive stroke centers (derivation and validation) including patients with anterior circulation LVOS. ICAD cases were matched for age / sex (1:1) to non-ICAD controls and stepwise logistic regression utilized for various clinical and radiological (NCCT, CTA and CTP) variables. Calibration slope / intercept as well as the area under curve (auROC) were assessed. Results: Of 2870 MTs within the study period, 174 anterior circulation ICAD (6.6%) were matched with 174 controls (n=348) in the derivation cohort. Multivariable analysis β coefficients lead to a 20 point-scale: absence of AF (5), vascular risk factor burden (1 for each: hypertension, diabetes, smoking, hyperlipidemia), CTA multifocal ICAD (3), absence of cortical infarcts (3), presence of borderzone infarct (3), calcium at the siphon (2). The validation cohort comprised 75 ICAD patients (6.9% of 1359 MTs) and 75 controls. AuROC for the derivation cohort was 0.88(0.84-0.91) while for the validation cohort 0.82(0.73-0.89). Calibration slope and intercept showed a good fit for the development cohort although with overestimated risk for the validation cohort. After intercept adjustment, the overestimation was corrected (intercept 0; 95%CI -0.5-0.5 / slope 0.8 95%CI 0.5-1.1). In the full cohort (n=498), ≥ 11 points showed the best performance for distinguishing ICAD from non-ICAD patients, with a sensitivity 0.71 (0.65-0.78) and specificity 0.82 (0.77-0.87), a positive likelihood ratio of 3.92 (2.92, 5.28) and a negative LR of 0.35 (0.28, 0.44). Scores ≥ 12 showed 90% specificity, although sensitivity of 63% (55%-69%). Conclusion: We developed a predictive scoring system for pre-procedural diagnosis of ICAD LVOS with satisfactory discrimination and calibration based on clinical and non-invasive radiological data.

Vascular risk factors are a major contributor to cognitive impairment and degenerative dementia in India

AbstractBackgroundThe burden of vascular contribution to cognitive impairment and dementia is high in low and middle‐income countries (LMIC) like India. It is crucial to determine burden of vascular contribution to dementia in India, to develop effective preventive and treatment strategies. The aim of the study was to determine the prevalence of vascular risk factors across the spectrum of cognitive impairment and dementia in a large dementia cohort in South India.MethodPatients with cognitive impairment and dementia from the dementia registries of two University referral hospitals in South India were included. All patients underwent clinical, cognitive and imaging study and standard criteria were used to diagnose MCI, AD, FTD, VaD and mixed dementia. Vascular risk factor profile was determined in patients, and the presence of hypertension, diabetes, cardiac disease, stroke, smoking and chronic alcoholism were noted.ResultOf a total 1811 patients with cognitive impairment, 180 (9.9%) patients were diagnosed to have MCI, 517 (28.5%) AD, 205 (11.3%) FTD, 844 (46.6%) had VaD &amp; 64 (3.5%) had mixed dementia. Overall, hypertension was the most prevalent vascular risk factor (62.7%) followed by stroke (46.6%). 35.5% of patients had diabetes mellitus(DM), 15.2% had chronic alcoholism, 14.4% were smokers and 14.2% had history of cardiac disorders.Hypertension was most commonly encountered in patients with AD (76.4%), followed by mixed Dementia (68.75%), VaD (63.4%), MCI (44.4%) and FTD (39.5%).DM was present in a high proportion of all subtypes of cognitive impairment and dementia (24.4% to 46.8%). The proportion of patients with stroke was highest in VaD (82.1%), but was also associated with one‐fourth of patients with AD and 15% of patients with mixed dementia. Frequency of smoking, chronic alcoholism and cardiac disease was highest in mixed dementia and VaD.ConclusionOur results demonstrate that a large burden of vascular risk factors exist in all forms of cognitive impairment and dementia in the Indian context. Hypertension and diabetes were found to be commonly associated with neurodegenerative dementia, in addition to vascular and mixed dementia. This large burden of vascular contribution represents needs and an opportunity to implement strategies to reduce burden of dementia in India and other LMICs

Mediation of the Association Between Vascular Risk Factors and Depressive Symptoms by C-Reactive Protein

BackgroundThis study examined whether C-reactive protein (CRP), a marker of low-grade systemic inflammation, mediates the association between vascular risk factor (VRF) burden and depressive symptoms. MethodsWe drew on the prospective design of the UK Biobank to include participants with longitudinal data on VRF burden, CRP, and depressive symptoms. Total, direct, and indirect effects were estimated using regression-based mediation models while controlling for confounding by sociodemographic factors, baseline CRP, and baseline depression. Sensitivity analyses probed the robustness of results to unmeasured confounding. ResultsWe analyzed data from 10,470 participants from the UK Biobank (mean age = 56.75 years at baseline). Net of covariates, VRFs at baseline were associated with higher depressive symptoms at follow-up (total effect = 0.099; 95% CI, 0.002–0.163). CRP mediated this association (indirect effect = 0.010; 95% CI, 0.004–0.017), accounting for 10.0% (95% CI, 0.3%–30.0%) of the total effect of VRF burden on depressive symptoms. Exploratory analyses suggested that the total and indirect effects pertained to somatic depressive symptoms (tiredness and appetite). ConclusionsThese results suggest that inflammation-promoting effects of VRFs may contribute to depressive symptoms in mid- and later life. However, the mediating pathway via CRP explains only a small part of the association between VRFs and depression after accounting for important covariates and may pertain to specific depressive symptoms. Future studies leveraging similar longitudinal designs are needed to further disentangle the time-varying effects between VRFs, inflammation, and certain depressive symptoms while addressing important confounders.

Preexisting Depression and Ambulatory Status After Stroke: Florida-Puerto Rico Collaboration to Reduce Stroke Disparities.

Stroke is a global public health burden, and therefore it is critical to identify modifiable risk factors to reduce stroke incidence and improve outcomes. Depression is such a risk factor; however, the association between preexisting depression and stroke outcomes, such as independent ambulation, is not well studied, especially among racial-ethnic minority groups. To address this gap in the literature, effects of preexisting depression on ambulatory status at hospital discharge after stroke were evaluated among individuals participating in the racially and ethnically diverse Florida-Puerto Rico Collaboration to Reduce Stroke Disparities project. Data were analyzed from a total of 42,031 ischemic stroke patients, who were independently ambulatory prior to their stroke, after discharge from 84 hospitals between 2014 and 2017. Preexisting depression was confirmed by medical history or antidepressant medication use. Multilevel multivariate logistic regression analyses were used to assess the association of preexisting depression with independent ambulation at hospital discharge. Effects of sex and race-ethnicity on this association were examined. Of 42,031 participants (mean±SD age=70.4±14.2 years; 48% were female; race-ethnicity: 16% Black, 12% Hispanic living in Florida, and 7% Hispanic living in Puerto Rico), 6,379 (15%) had preexisting depression. Compared with participants without depression, those with preexisting depression were older, were more likely to be female and non-Hispanic White, and had a greater burden of vascular risk factors or comorbid conditions. Independent ambulation at hospital discharge was less frequent among women, Black participants, and individuals with vascular risk factors or comorbid conditions. In multivariate models, preexisting depression decreased the likelihood of independent ambulation at discharge (odds ratio=0.88, 95% CI=0.81, 0.97). No interactions were found between preexisting depression and race-ethnicity or sex. Preexisting depression was independently associated with dependent ambulation at hospital discharge after stroke, regardless of sex and race-ethnicity. Treating depression may contribute to primary stroke prevention and could improve ambulatory status at discharge.

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

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. 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. 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. 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.

Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer

ObjectivesTo evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.MethodsCancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history...

Abstract WP75: Association Between Sleep-disordered Breathing And Post-stroke Fatigue

Background: Post-stroke fatigue (PSF) is a common and often disabling symptom, the etiology of which is poorly understood. Sleep-disordered breathing (SDB) is also highly prevalent among stroke survivors. We explored the relationship between SDB and PSF over time in a bi-ethnic cohort. Methods: Ischemic stroke (IS) patients within the Brain Attack Surveillance in Corpus Christi (BASIC) project were identified through active and passive surveillance, and were offered home SDB screening with a well-validated cardiopulmonary sleep apnea testing device, the ApneaLink Plus. The primary exposure was the respiratory event index (REI). The primary outcome was PSF as measured by the SF-36 vitality scale (lower scores reflect greater fatigue). SDB and PSF were measured at baseline, 3, 6, and 12 months post-stroke. A linear regression model, using GEE to account for repeated measures, was used to examine the associations between REI and PSF at each time point adjusting for sociodemographics, stroke severity, depressive symptoms, pre-stroke fatigue, and comorbidities. Results: SDB screening and at least one PSF assessment were completed by 462 IS patients, who were 44% female, 61% Mexican American (MA), 26% non-Hispanic white, 7% Black, and 5% other race/ethnicity. Median NIHSS was 2 (IQR: 1-4). Multivariable regression model results are presented in the Table. Higher REI at 3 months was associated with greater PSF at 3 months (β= -1.87, 95%CI -3.47, -0.27), but there was no association between REI and PSF at 6 or 12 months. Across timepoints, female sex, depressive symptoms at time of assessment, pre-stroke medication for depression, higher levels of pre-stroke fatigue, and vascular risk factor burden were associated with greater PSF, whereas MA ethnicity was associated with less PSF. Conclusions: Higher REI was associated with greater PSF in the early post-stroke period, but no association was observed at 6 months and beyond. MA ethnicity seems to be protective against PSF.

ADAMTS-13 activity in stroke of known and unknown cause: Relation to vascular risk factor burden.

The identification of the underlying mechanism in ischemic stroke has important implications for secondary prevention. A disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS-13) has antithrombotic properties and was repeatedly implicated in the pathophysiology of stroke. In this study, we, therefore, aimed to investigate whether ADAMTS-13 is associated with stroke etiology and the burden of vascular risk factors. We determined ADAMTS-13 activity in two prospectively recruited stroke cohorts in the long-term course after the event. Cohort 1 (n = 88) consisted of patients who suffered a stroke due to embolic stroke of undetermined source (ESUS), cardioembolic stroke due to atrial fibrillation (AF), large-artery atherosclerosis, or small vessel disease. In cohort 2, patients with cryptogenic stroke and patent foramen ovale (PFO) scheduled for PFO closure (n = 38) were enrolled. As measures of vascular risk factor burden, the CHA2DS2VASC score, the Essen Stroke Risk Score (ESRS), and the Risk of Paradoxical Embolism (RoPE) score were calculated, as appropriate. ADAMTS-13 activity was lower in patients with AF-related stroke compared to patients with ESUS (p = 0.0227), which was, however, due to confounding by vascular risk factors. ADAMTS-13 activity inversely correlated with the ESRS (r = -0.452, p < 0.001) and CHA2DS2VASC (r = -0.375, p < 0.001) in cohort 1. In accordance with these findings, we found a positive correlation between ADAMTS-13 activity and the RoPE score in cohort 2 (r = 0.413, p = 0.010). ADAMTS-13 activity is inversely correlated with the number of vascular risk factors across different stroke etiologies. Further study is warranted to establish ADAMTS-13 as a mediator of cerebrovascular risk.

Novel grading system for CADASIL severity: A multicenter cross-sectional study

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited progressive cerebral microangiopathy with considerable phenotypic variability. The purpose of this study was to describe the generalizability of a recently proposed grading system of CADASIL across multiple centers in the United States. MethodsElectronic medical records (EMR) of an initial neurological assessment of adult patients with confirmed CADASIL were reviewed across 5 tertiary referral medical centers with expertise in CADASIL. Demographic, vascular risk factors, and neuroimaging data were abstracted from EMR. Patients were categorized into groups according to the proposed CADASIL grading system: Grade 0 (asymptomatic), Grade 1 (migraine only), Grade 2 (stroke, TIA, or MCI), Grade 3 (gait assistance or dementia), and Grade 4 (bedbound or end-stage). Inter-rater reliability (IRR) of grading was tested in a subset of cases. ResultsWe identified 138 patients with a mean age of 50.9 ± 13.1 years, and 57.2% were female. The IRR was acceptable over 33 cases (κ=0.855, SD 0.078, p<0.001) with 81.8% being concordant. There were 15 patients (10.9%) with Grade 0, 50 (36.2%) with Grade 1, 61 (44.2%) with Grade 2, 12 (8.7%) with Grade 3, and none with Grade 4. Patients with a lower severity grade (grade 0 vs 3) tended to be younger (49.5 vs. 61.9 years) and had a lower prevalence of hypertension (50% vs. 20%, p = 0.027) and diabetes mellitus (0% vs. 25%, p = 0.018). A higher severity grade was associated with an increased number of vascular risk factors (p = 0.02) and independently associated with hypertension and diabetes (p<0.05). Comparing Grade 0 vs. 3, cortical thickness tended to be greater (2.06 vs. 1.87 mm; p = 0.06) and white matter hyperintensity volume tended to be lower (54.7 vs. 72.5 ml; p = 0.73), but the differences did not reach significance. ConclusionThe CADASIL severity grading system is a pragmatic, reliable system for characterizing CADASIL phenotype that does not require testing beyond that done in standard clinical practice. Higher severity grades tended to have a higher vascular risk factor burden. This system offers a simple method of categorizing CADASIL patients which may help to describe populations in observational and interventional studies.

Structural network efficiency mediates the association between glymphatic function and cognition in mild VCI: a DTI-ALPS study.

Background and objective: Vascular cognitive impairment (VCI) can be caused by multiple types of cerebrovascular pathology and is considered a network disconnection disorder. The heterogeneity hinders research progress in VCI. Glymphatic failure has been considered as a key common pathway to dementia recently. The emergence of a new method, Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS), makes it possible to investigate the changes of the glymphatic function in humans non-invasively. We aimed to investigate alterations of glymphatic function in VCI and its potential impact on network connectivity. Methods: We recruited 79 patients with mild VCI, including 40 with cerebral small vessel disease cognitive impairment (SVCI) and 39 with post-stroke cognitive impairment (PSCI); and, 77 normal cognitive (NC) subjects were recruited. All subjects received neuropsychological assessments and multimodal magnetic resonance imaging scans. ALPS-index was calculated and structural networks were constructed by deterministic tractography, and then, the topological metrics of these structural connectivity were evaluated. Results: The ALPS-index of VCI patients was significantly lower than that of NC subjects (P < 0.001). Multiple linear regression analysis showed that ALPS-index affects cognitive function independently (β = 0.411, P < 0.001). The results of correlation analysis showed that the ALPS-index was correlated with overall vascular risk factor burden (r = -0.263, P = 0.001) and multiple cerebrovascular pathologies (P < 0.05). In addition, global efficiency (Eg) of network was correlated with ALPS-index in both SVCI (r = 0.348, P = 0.028) and PSCI (r = 0.732, P < 0.001) patients. Finally, the results of mediation analysis showed that Eg partially mediated in the impact of glymphatic dysfunction on cognitive impairment (indirect effect = 7.46, 95% CI 4.08-11.48). Conclusion: In both major subtypes of VCI, the ALPS-index was decreased, indicating impaired glymphatic function in VCI. Glymphatic dysfunction may affect cognitive function in VCI by disrupting network connectivity, and, may be a potential common pathological mechanism of VCI. ALPS-index is expected to become an emerging imaging marker for VCI.

Association between antiplatelet medication and cerebral microbleeds in stroke-free population.

BACKGROUNDCerebral microbleeds (CMBs) may increase the risk of future intracerebral hemorrhage and ischemic stroke. However, It is unclear whether antiplatelet medication is associated with CMBs. This study aimed to investigate the association between antiplatelet medication and CMBs in a community-based stroke-free population.METHODSIn this cross-sectional study, stroke-free participants aged 18–85 years were recruited from a community in Beijing, China. Demographic, clinical, and antiplatelet medication data were collected through a questionnaire, and all participants underwent blood tests and brain magnetic resonance imaging at 3.0T. The presence, count, and location of CMBs were evaluated using susceptibility-weighted imaging. The association between antiplatelet medication and the presence of CMBs was analyzed using multivariable logistic regression. The associations between antiplatelet medication and CMBs by location (lobar, deep brain or infratentorial, and mixed regions) were also analyzed using multinomial logistic regression. A linear regression analysis was conducted to determine the association between antiplatelet medication and the log-transformed number of CMBs.RESULTSOf the 544 participants (mean age: 58.65 ± 13.66 years, 217 males), 119 participants (21.88%) had CMBs, and 64 participants (11.76%) used antiplatelet medication. Antiplatelet medication was found to be associated with CMBs at any location [odds ratio (OR) = 2.39, 95% CI: 1.24–4.58] and lobar region (OR = 2.83, 95% CI: 1.36–5.86), but not with the number of CMBs (β = 0.14, 95% CI: -0.21–0.48). Among antiplatelet medications, aspirin use was found to be associated with any CMB (OR = 3.17, 95% CI: 1.49–6.72) and lobar CMBs (OR = 3.61, 95% CI: 1.57–8.26).CONCLUSIONSAntiplatelet medication was associated with CMBs in stroke-free participants, particularly lobar CMBs. Among antiplatelet medications, aspirin use was associated with any CMB and lobar CMBs. Our findings suggest that it might be essential to optimize the management of antiplatelet medication in the stroke-free population with a higher burden of vascular risk factors to reduce the potential risk of CMBs.

Determinants and Temporal Dynamics of Cerebral Small Vessel Disease: 14-Year Follow-Up

Background:The aim of this study is to investigate the temporal dynamics of small vessel disease (SVD) and the effect of vascular risk factors and baseline SVD burden on progression of SVD with 4 neuroimaging assessments over 14 years in patients with SVD.Methods:Five hundred three patients with sporadic SVD (50–85 years) from the ongoing prospective cohort study (RUN DMC [Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort]) underwent baseline assessment in 2006 and follow-up in 2011, 2015, and 2020. Vascular risk factors and magnetic resonance imaging markers of SVD were evaluated. Linear mixed-effects model and negative binomial regression model were used to examine the determinants of temporal dynamics of SVD markers.Results:A total of 382 SVD patients (mean [SD] 64.1 [8.4]; 219 men and 163 women) who underwent at least 2 serial brain magnetic resonance imaging scans were included, with mean (SD) follow-up of 11.15 (3.32) years. We found a highly variable temporal course of SVD. Mean (SD) WMH progression rate was 0.6 (0.74) mL/y (range, 0.02–4.73 mL/y) and 13.6% of patients had incident lacunes (1.03%/y) over the 14-year follow-up. About 4% showed net WMH regression over 14 years, whereas 38 out of 361 (10.5%), 5 out of 296 (2%), and 61 out of 231 (26%) patients showed WMH regression for the intervals 2006 to 2011, 2011 to 2015, and 2015 to 2020, respectively. Of these, 29 (76%), 5 (100%), and 57 (93%) showed overall progression across the 14-year follow-up, and the net overall WMH change between first and last scan considering all participants was a net average WMH progression over the 14-year period. Older age was a strong predictor for faster WMH progression and incident lacunes. Patients with mild baseline WMH rarely progressed to severe WMH. In addition, both baseline burden of SVD lesions and vascular risk factors independently and synergistically predicted WMH progression, whereas only baseline SVD burden predicted incident lacunes over the 14-year follow-up.Conclusions:SVD shows pronounced progression over time, but mild WMH rarely progresses to clinically severe WMH. WMH regression is noteworthy during some magnetic resonance imaging intervals, although it could be overall compensated by progression over the long follow-up.

Abstract 065: Educational Attainment And Dementia Risk: Mediation By Vascular Risk Factors At Mid-life In The Atherosclerosis Risk In Communities (ARIC) Study

Background: Dementia prevention largely focuses on the modification of vascular risk factors and is particularly important among stroke survivors, who have the highest burden of vascular risk factors and are at elevated risk of dementia. Low educational attainment is a risk factor not only for worse vascular profiles at midlife but also for incident dementia. It is unclear to what extent the relationship between education and dementia is mediated through these vascular risk factors. Methods: In a cohort of 14,059 Black and White older adults in four U.S. communities, we assessed the relationship between education and dementia among all participants and, separately, among those with incident stroke. We used causal mediation analysis to assess multiple mediation by midlife hypertension, diabetes, BMI and smoking of the relationship between educational attainment and dementia. Results: Participants with less education had higher prevalence of mid-life risk factors. Lower education was associated with 60% higher risk of dementia and 40% higher risk of post-stroke dementia. About half of the association between education and dementia was mediated through vascular risk factors (Table 1). Conclusion: A substantial proportion of the relationship between education and dementia risk is indeed not mediated through mid-life vascular risk factors. The association between education and dementia was weaker in the high-risk participants who have had an incident stroke, indicating that more proximal causes such as vascular disease prior to the stroke superseded the distal cause of differences in educational attainment. As such, any mediated effect of education on dementia is likely through vascular risk factors earlier on in the life-course. Our findings suggest that dementia prevention efforts must also address disparities in socioeconomic resources as well as other mediating pathways.

Abstract WP224: Trends In Self-reported Stroke And Myocardial Infarction Prevalence And Associated Modifiable Risk Factors Within Race/ethnicity Strata In The United States From 2011-2019

Background: Stroke and myocardial infarction (MI) prevalence varies by race/ethnicity, as do the risk factors. Methods: We included biyearly data from the 2011-2019 Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults (age ≥18) in the United States. We describe survey-weighted prevalence of self-reported stroke and MI by race and ethnicity. We also describe the prevalence of modifiable vascular risk factors in patients with stroke and MI. Results: The weighted number of U.S. participants represented in BRFSS surveys increased from 237,404,549 in 2011 to 251,703,709 in 2019. Stroke prevalence increased from 2.9% in 2011 to 3.4% in 2019 (&lt;0.001), while MI prevalence did not change over time (4.3% in 2011; 4.2% in 2019). The prevalence of stroke and MI was highest in American Indian/Alaskan Natives (AI/AN) at 5.6% and 7.5% in 2011 and 2019, respectively, compared to 3.2% and 4.8% for whites (p&lt;0.001). Prevalence trends by race/ethnicity are in Figure 1. Modifiable risk factors are in Tables 1&amp;2, which show that AI/AN consistently have the highest or second highest proportion with ≥4 risk factors. Conclusion: Prevalence of self-reported stroke, but not MI, is increasing in the United States. AI/AN consistently had the highest prevalence from 2011-2019 and the highest overall burden of modifiable vascular risk factors, rendering this group more vulnerable to a recurrent vascular event.