bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 100: Association of the Mediterranean Diet with White Matter Integrity Among Hispanics/Latinos. Final Results from the Study of Latinos-Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) Ancillary Study
Authors: Trifan Gabriela , Moustafa Bayan , Isasi Carmen , Lipton Richard , Sotres-Alvarez Daniela , Cai Jianwen , Tarraf Wassim , Stickel Ariana , Mattei Josiemer , Talavera Gregory , Maillard Pauline , Daviglus Martha , Gonzalez Hector M , DeCarli Charles , Testai Fernando
Published: January 2025

Background:
High adherence to the Mediterranean Diet (MeDi) was associated with better cognitive performance and decreased memory decline among Hispanic or Latino adults.

Objective:
Investigate if higher adherence to the MeDi improves white matter (WM) integrity among Hispanic/Latino adults and if this effect is mediated by cardiovascular health (CVH).

Methods:
We included 2,774 participants from the Study of Latinos-Investigation of Neurocognitive Aging-MRI Ancillary Study. Participants completed 24-hour dietary recalls at baseline (2008-2011) which were used to calculate a MeDi score (MeDiS, range 0-9). Brain MRI and diffusion tensor images were collected between 2018 and 2022 on a 3T MRI scanner using a standardized protocol. WM integrity was ascertained using WM hyperintensity (WMH) volume and fractional anisotropy (FA). WMH volumes were residualized for total cranial volume and Ln-transformed prior to analysis. The association of MRI outcomes with MeDiS and its components was investigated using weighted linear regression analysis with complex survey design adjusting for age, sex, sociodemographic characteristics. Cardiovascular health was assessed using the Life’s Simple 7 (LS7, range 0-14) score. The mediating effect of LS7 on the primary outcome was reported as Average Causal Mediation Effects (ACME) and Average Direct Effects (ADE). Statistical significance was set at p<0.05.

Results:
Mean age (95% CI) at MRI scan was 64.0 (63.4 to 65.2) and 44% were males. Mean MeDiS was 5.01 (4.89 to 5.12) and LS7 was 7.1 (7.0 to 7.3). In our fully adjusted model, increasing MeDi adherence was associated with decreased LnWMH volume (β=-0.07, 95% CI -0.10 to -0.03) and increased FA (β=0.002, 95% CI 0.001 to 0.003). Increasing LS7 scores partially mediated the relationship between MeDiS and WMHs (ACME=-0.01, ADE=-0.08, p<0.05, percent mediation=9%) and between MeDiS and FA (ACME=0.0001, ADE=0.002, p<0.01, percent mediated=8%). Among the different MeDi components, consumption of whole grains and fish above sex-specific energy adjusted energy median intake predicted lower WMH volume and increase FA (p<0.05 for both).

Conclusions:
Among diverse Hispanic/Latino adults, high MeDi adherence was associated with preserved WM integrity. This association was partially mediated by CVH. This suggests that the beneficial effect of MeDi on brain health is not fully explained by vascular risk factors. A culturally tailored MeDi may preserve brain health among Hispanic/Latino adults.
Abstract 101: Brain arteriolar remodeling relates to Alzheimer pathology and neuroinflammation
Authors: Garzon Mancera Nicolas , Barreto Brenno , Hassett James Stokes , Dohmen Tren , Sole Guardia Gemma , Kozii Khrystyna , Zambrano Daniela , Ramaswamy Srinath , Cadena Tejada Angel , Spagnolo-Allende Antonio , Flaherty Delany , Orlando Quiiroles Lucas , Chou Lindsey , Paiva Bueno Pedro , Yang Dixon , Kiliaan Amanda , Bos Daniel , Dwork Andrew , schneider julie , Teich Andrew , Gutierrez Jose
Published: January 2025

Introduction:
Previous studies have shown an association between vascular disease and Alzheimer’s disease, but there are few studies have considered a relationship between brain arterial remodeling and biomarkers of Alzheimer's disease. Our study aims to find the association between specific arterial characteristics in brain arterial remodeling and Alzheimer's pathology.

Method:
We analyzed 132 brain autopsy cases from the Brain Arterial Remodeling Study (BARS), a collection of brains from multiple brain banks in the United States and abroad. Brain sections were obtained systematically by each brain bank, and the anatomical location was harmonized across the banks. The brain slides were stained with LH&E to measure the lumen and wall thickness of the pial, CSF-floating small arteries, parenchymal arteries, and arterioles. Then lumen area, wall thickness, lumen-to-wall ratio (LWR), and wall proportion (which serves as a measure of vessel stenosis) were calculated. We used immunohistochemistry to stain for beta-amyloid, phospho-tau, and Iba1, a measure of microglia. Each stained slide was processed automatically using Visiopharm (version 2021.12) by color thresholding and pattern detection to quantify the number of amyloid plaques and microglial (Iba1+ cells) per 100 µm
2
and the percentage of tissue area stained positive by phospho-tau, and the number of microglial cells per 100 µm
2
.

Results:
Overall, a thicker arterial wall was associated with a greater area of tau staining and a lower lumen-to-wall ratio (suggestive of inward remodeling) was associated with a higher number of microglial cells (table 1). There was a statistical interaction between measures of arterial remodeling by anatomical location (pial vs. parenchymal, P<0.01) and amyloid measures. Stratifying by arterial anatomical location, however, demonstrated that parenchymal arteries with large lumen (B=0.12 ±0.03 per µm
2
, P<0.001) and thicker arterial wall (B=1.10 ± 0.18 per µm
2
, P<0.001) had a higher number of amyloid plaques per 100 µm
2
.

Conclusion:
Brain arteries immediately supplying the brain and their parenchymal offsprings related to measures of tau phosphorylation and neuroinflammation. Parenchymal arteries and arterioles that are dilated proportional to their wall thickness also relate to a greater load of amyloid deposition. Further investigation is needed to clarify these relationships.
Abstract 110: Myelinated Fiber Innervation of Human Intracranial Arteries: A Regulatory Role in Atherosclerosis
Authors: Wang Zijue , Yuan Weizhuang , He Yangzhige , Ding Manqiu , Ma Chao , Chen Zhen , Wang Naili , Xu Yan , Xu Weihai
Published: January 2025

Background:
Recent studies have shown that the autonomic nervous system plays a crucial role in regulating the initiation and progression of atherosclerosis in peripheral arteries. Animal studies suggest that intracranial arteries are innervated by unmyelinated autonomic nerves. However, the role of the autonomic nervous system in human intracranial atherosclerosis remains poorly understood.

Methods:
We utilized intracranial arterial tissue from human autopsies and employed single-cell RNA sequencing, transmission electron microscopy, and multiple immunofluorescence staining to investigate the mechanisms underlying the initiation and progression of atherosclerosis.

Results:
We identified a population of Schwann cells in the walls of intracranial arteries. This discovery challenges conventional understanding, as Schwann cells are traditionally associated with the peripheral nervous system, and their presence in intracranial arteries has not been previously reported. Using transmission electron microscopy, we further found lamellar myelin structures within the arterial media, and the number of myelin sheaths was higher in the plague group than in the control group, suggesting that Schwann cells may participate in myelination within the arterial wall and then influence plaque progression. To elucidate the cellular communication networks involving Schwann cells, we utilized the CellChat analytical framework and found that Schwann cells had robust crosstalk with vascular smooth muscle cells (VSMCs). These interactions were mediated by a complex network of signaling molecules, including those implicated in axon growth, axon guidance, and cell adhesion, suggesting that Schwann cells may actively modulate VSMCs behavior and influence the pathological remodeling of the arterial wall characteristic of atherosclerotic lesions. Multiple immunofluorescence staining revealed that the plaque group exhibited a greater density of nerve fiber innervation compared to the control group.

Conclusions:
Our study provides evidence that human intracranial arteries are innervated by myelinated fibers. Schwann cells may participate in the initiation and progression of intracranial atherosclerosis by facilitating axon growth and rearrangement. These results not only enhance our understanding of cellular diversity within atherosclerotic lesions but also highlight Schwann cells as a potential therapeutic target.
Abstract 112: Clinical scale MSC-derived extracellular vesicles enhance poststroke neuroplasticity in a non-human primate model of stroke
Authors: Bang Oh Young , Son Jeong Pyo , Kim Eun Hee , Chopp Michael
Published: January 2025

Introduction:
Stroke is a leading cause of death and disability. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) has shown considerable promise in rodent models of stroke. However, the therapeutic efficacy and safety of clinical-scale MSC-EVs for ischemic stroke are not well elucidated, especially in non-human primates.

Methods:
We developed a scalable production method for MSC-EVs using a 3D bioprocessing platform. EVs were isolated with filter and tangential flow filtration and characterized through electron microscopy, nanoparticle tracking analysis, nanoflow cytometry analysis, proteomic and lipodomic analysis using mass spectrometry, and RNA sequencing. We determined the appropriate dosage and frequency of intravenous administration of EVs in a mouse stroke model. We then confirmed the efficacy of EVs in a marmoset model of stroke. Improvement in behavioral tests and MRI-based neuroplasticity were compared between the control and EV groups through blind evaluation. The proteome profiles of the infarcted hemisphere were also evaluated.

Results:
EV products showed suitable lot-to-lot consistent. In a mouse stroke model, intravenous administration of a dose of 6 x 10
8
EVs for five days resulted in the smallest infarct volume and improvement in motor function, with no significant toxicity observed at the tested dosages in the preclinical toxicity studies. Intravenous administration of an equivalent dose (3.5 x 10
9
EVs for five days) in a marmoset model of stroke improved motor functions and anatomical connectivity on diffusion tensor imaging and reduced infarct volume. Proteomics analyses of the infarcted region indicated that EV treatment promoted neurogenesis and synapse function-related protein expression.

Conclusions:
This study is the first to demonstrate that a clinical-scale EV product is safe and significantly enhances functions recovery and neuroplasticity in a non-human primate model of stroke, offering a promising treatment for human stroke.
Abstract 121: Views from the Frontlines: Perspectives of Young Adult Caregivers on Unmet Needs after Severe Stroke
Authors: Lutz Barbara , Jones Andrea , Zahuranec Darin , Creutzfeldt Claire
Published: January 2025

Introduction:
An estimated 10-14% of all strokes occur in individuals under age 50, with an increase of ~15% from 2011-2022. Severe strokes in young adults affect the family unit quality of life. Caregivers of young stroke survivors often must work, raise children, and care for the patient who often has severe functional limitations. We explored unmet needs of young adult caregivers with severe stroke and their perspectives on post-stroke supportive interventions.

Methods:
19 caregivers of patients with severe stroke were recruited to participate in qualitative interviews as part of a large study to understand symptom burden and needs of patients and families following severe stroke. Two interviews were conducted at 1-3 months and 6-9 months post-discharge. Using thematic and comparative analyses, we analyzed interviews with a subset of 10 working aged caregivers (20 interviews total) focused on 2 questions: 1) How can healthcare providers support caregivers, and 2) What advice would you offer caregivers in a similar situation? Common themes were identified and grouped into categories focused on unmet support needs and potential interventions.

Results:
Participants noted 3 areas of unmet needs: emotional, tangible, and cognitive (written and verbal information) support. They also indicated a need for a single point of contact beginning at hospitalization and continuing several months post-discharge. Participants were overwhelmed by the vast amounts of written information which was often discarded. Some respondents noted an affinity for technological contact in the form of electronic charts, etc. Others were unable to use the systems in place. Caregivers often had to make critical decisions based on little understanding of the daunting medical crisis and uncertain prognosis for recovery. Respondents advised patience, strong advocacy, and asking questions until understanding was achieved.

Conclusion:
Caregivers’ desire for a single point of contact throughout hospitalization and recovery is at odds with the current fragmented model of care in most US hospitals. A nurse, social worker, or a highly trained volunteer could serve as in this role to provide anticipatory guidance related to unpredictability of stroke recovery, parcel tailored information, make requisite resource referrals, and help caregivers navigate the myriad systems, especially post discharge. Further study of the optimal methods to support young caregivers after stroke is warranted.
Abstract 144: Mobile Stroke Unit Management and Outcomes in Undifferentiated Patients with Stroke-Like Symptoms in the Prehospital Setting: A Nationwide Cohort Study
Authors: Mac Grory Brian , Sun Jie-Lena , Alhanti Brooke , Lusk Jay , Li Fan , Adeoye Opeolu , Furie Karen , Hasan David , Messe Steven , Sheth Kevin , Schwamm Lee , Smith Eric , Bhatt Deepak , Fonarow Gregg , Saver Jeffrey , Xian Ying , Grotta James
Published: January 2025

Introduction:
Prospective, controlled clinical trials have suggested that prehospital management in a mobile stroke unit (MSU) improves functional outcomes in intravenous (IV) thrombolysis-eligible patients. However, because MSUs are dispatched prior to knowledge of the diagnosis, an examination of their real-world effectiveness must include all patients for whom stroke is suspected. The objective of this study was to determine the association between MSU management vs. EMS management and outcomes in all patients with suspected stroke in the prehospital setting.

Methods:
We performed a retrospective, observational, cohort study from the American Heart Association’s Get With The Guidelines®-Stroke (GWTG-Stroke) Program between August 1
st
2018 and January 31
st
2023. At participating hospitals receiving both MSU-managed and standard EMS-managed patients, all patients with stroke-like symptoms in the prehospital setting were analyzed. The primary efficacy end point was the level of global disability assessed with the utility-weighted modified Rankin Scale (UW-mRS; rage 0.00 – 1.00). The secondary efficacy end point was ambulatory status. The co-primary safety end points were symptomatic intracranial hemorrhage (sICH) and in-hospital mortality.

Results:
Of 108,684 patients (median age 73 [Q1,Q3: 62,83]; 51.2% female), 4,218 (3.9%) received prehospital management in an MSU. Prehospital management in an MSU was associated with a better score on the UW-mRS at discharge (adjusted mean difference 0.05 [95% CI: 0.03 – 0.06]) and a higher likelihood of independent ambulation at discharge (51.0% [1,521/2,985] vs. 47.8% [31,450/79,699]; aRR 1.11 [95% CI: 1.08 – 1.15]; adjusted risk difference 5.2% [95% CI: 3.7 to 6.8]). There was no statistically significant difference in sICH (4.0% vs. 4.1%; aRR 1.02 [95% CI: 0.82 – 1.25]). There was a lower rate of in-hospital mortality (6.4% vs. 8.7%; aRR: 0.78 [95% CI: 0.71 to 0.87]) in MSU-treated patients.

Conclusions:
Among patients with stroke-like symptoms in the prehospital setting, prehospital management in an MSU compared with EMS management was associated with a significantly lower level of global disability. These findings support policy efforts to expand access to MSU care in the United States.
Abstract 145: New Oral Anticoagulant Therapy Versus Warfarin In Patients With Atrial Fibrillation And Previous Stroke or Transient Ischemic Attack. An Updated Meta-analysis.
Authors: OBI OGECHUKWU , Cavalcante Deivyd , Nweze Uchenna , Asonye Patricia , Lee Timothy
Published: January 2025

Background:
Patients with atrial fibrillation (AF) and previous stroke or transient ischemic attack (TIA) are at high risk of recurrent stroke. Data regarding the efficacy and safety of new oral anticoagulant therapy (NOAC) compared to warfarin in patients with previous strokes are lacking.

Method:
PubMed, Scopus and Cochrane databases were searched for both randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) that compared NOAC to warfarin in patients with AF and previous stroke or TIA and that reported the outcomes of cardiovascular death, death from any cause, disabling or fatal stroke, gastrointestinal major bleeding, hemorrhagic stroke, intracranial bleeding, major bleeding, overall stroke etc. Heterogeneity was examined using I
2
statistics.

Results:
We included 7 RCTs and 2 non-RCTs comparing NOAC to warfarin in patients with atrial fibrillation and previous stroke or TIA. The pooled results showed that cardiovascular death (4.9% vs 5.2% respectively; OR = 0.92; 95% CI [0.78, 1.08]; I
2
= 34%; p = 0.298), death from any cause (6.7% vs 7.5% respectively; OR = 0.88; 95% CI [0.77, 1.01]; I
2
= 59%; p = 0.066), disabling or fatal stroke (2.4% vs 2.9% respectively; OR = 0.83; 95% CI [0.69, 1.01]; I
2
= 0%; p = 0.058), gastrointestinal major bleeding (2.4% vs 1.3% respectively; OR = 1.95; 95% CI [0.65, 5.83]; I
2
= 80%; p = 0.231), and ischemic or unknown type of stroke (RR = 0.86; 95% CI [0.69, 1.08]; I
2
= 48%; p = 0.200) are not statistically different between the NAOC group and warfarin group. However, hemorrhagic stroke (RR = 0.46; 95% CI [0.30, 0.69]; I
2
= 24%; p < 0.001), intracranial bleeding (0.82% vs 1.8% respectively; OR = 0.41; 95% CI [0.25, 0.66]; I
2
= 43%; p < 0.001), major bleeding (RR = 0.83; 95% CI [0.71, 0.98]; I
2
= 9%; p = 0.025), overall stroke (RR = 0.72; 95% CI [0.58, 0.89]; I
2
= 44%; p = 0.002) and stroke or systemic embolism (4.3% vs 5.0% respectively; OR = 0.84; 95% CI [0.73, 0.97]; I
2
= 0%; p = 0.015) are significantly reduced in the NAOC group compared to the warfarin group.

Conclusion:
In patients with atrial fibrillation and previous stroke or transient ischemic attack, treatment with NOAC did not show any significant difference compared with warfarin for outcomes of death from any cause, cardiovascular death, disabling or fatal stroke, and gastrointestinal major bleeding. NOAC reduces the risk of hemorrhagic stroke, intracranial bleeding, major bleeding, and overall stroke compared to warfarin.
Abstract 39: Timing of Intracranial Stent Placement and One month Stroke and/or Death Rates in Patients with High Grade Symptomatic Intracranial Stenosis: Pooled Analysis of SAMMPRIS and VISSIT Trials
Authors: Qureshi Adnan , Huang Yilun , Suri Fareed , Gomez Camilo
Published: January 2025

Background:
The Food and Drug Administration (FDA) recommended that intracranial stenting (ICAS) not be performed within 7 days of qualifying cerebral ischemic event due to high rates of 1-month stroke and/or death observed with Wingspan intracranial stent placement in Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial. However, a detailed analysis of the relationship between timing of ICAS and 1-month stroke and/or death has not been performed.

Methods:
We compared the rates of 1-month stroke and/or death associated with ICAS performed ≤7 days and those >7 days after qualifying cerebral ischemic event in patients recruited in two randomized multicenter trials (SAMMPRIS and Vitesse Intracranial Stent Study for Ischemic Stroke Therapy [VISSIT]. Both trials recruited patients aged ≥ 30 years and ≤ 80 years, who suffered from transient ischemic attack (TIA) or minor ischemic stroke related to high grade (70% to 99% in severity) stenosis in a major intracranial artery and used independent ascertainment for 1 month event rates. We performed logistic regression analysis to identify the effect of time interval strata between qualifying cerebral ischemic event and ICAS on 1-month stroke and/or death rate after adjusting for potential confounders.

Results:
A total of 108 and 170 patients underwent ICAS ≤7 days and >7 days after the qualifying cerebral ischemic event, respectively. Balloon expandable stent (BES) and self-expanding stent (SES) were used in 54 and 224 patients, respectively. The rates of 1-month stroke and death were 17 of 108 (15.7%) and 30 of 170 (17.6%) in patients treated ≤7 days and those >7 days after qualifying cerebral ischemic event, respectively (p=0.729). There was no difference in the 1-month stroke and/or death rate in patients who underwent ICAS ≤7 days and those >7 days after qualifying cerebral ischemic events (odds ratio 0.074, 95% confidence interval 0.28-2.41) after adjusting for age, gender, severity of stenosis strata, qualifying cerebral ischemic event type (TIA or minor ischemic stroke), and stent used (BES versus SES).

Conclusions:
We did not observe any increased risk of 1-month stroke and/or death in patients who underwent ICAS ≤7 days and those >7 days after the qualifying cerebral ischemic event. Delaying the ICAS according to current FDA recommendations may not be necessary when ICAS is indicated.
Abstract 4: Thrombolysis with Tenecteplase in Minor Disabling versus Non-disabling Stroke: Secondary Analysis of the TEMPO-2 Trial
Authors: Zhang Yiran , Buck Brian , Catanese Luciana , Strbian Daniel , Vatanpour Shabnam , Field Thalia , Choi Philip , Hill Michael , Coutts Shelagh
Published: January 2025

Introduction:
The tenecteplase versus standard of care for minor ischemic stroke with proven occlusion (TEMPO-2) trial showed that patients presenting with minor deficits up to 12 h do not benefit from intravenous thrombolysis. The trial included patients with minor but disabling deficits, mainly beyond 4.5 h, if they were not eligible for standard-of-care thrombolysis. We aimed to determine if intravenous tenecteplase improves outcomes in this subgroup of TEMPO-2 patients with disabling deficits.

Methods:
This was an exploratory secondary analysis of the TEMPO-2 trial, which randomized patients across 48 hospitals globally with minor acute ischemic stroke (NIHSS score 0-5) and intracranial occlusion or focal perfusion abnormality within 12 h from stroke onset to intravenous tenecteplase (0.25 mg/kg) or non-thrombolytic standard of care. Adopting an available definition for disabling stroke from the TREAT Task Force consensus (Table 1), we compared efficacy and safety outcomes between treatment arms for participants with non-disabling versus disabling syndromes at presentation.

Results:
Among 886 patients, 786 (88.7%) and 100 (11.3%) were identified to have non-disabling and disabling deficits, respectively. Patients with disabling deficits had higher baseline NIHSS scores (4 vs 2, P<0.001), later presentations (288min vs 133min, P<0.001) and longer onset to treatment time (411min vs 278min, P<001). There was no evidence of treatment effect heterogeneity between disabling and non-disabling groups (P
interaction
= 0.22). However, there were nominally fewer excellent outcomes at 90 days (mRS 0-1) with tenecteplase compared with standard of care in the disabling group (non-disabling: 72.0% vs 72.5%, P=0.936; disabling: 47.2% vs 61.7%, P=0.164). No difference in symptomatic ICH was found but an interaction existed with treatment arms and presence of disabling stroke regarding any hemorrhage on follow-up neuroimaging (non-disabling: tenecteplase 13.5% vs control 10.0%, P=0.146; disabling: tenecteplase 20.8% vs control 2.1%, P=0.005. P
interaction
= 0.049).

Conclusions:
The TREAT Task Force definition of disabling stroke did not modify the neutral treatment effect of intravenous tenecteplase in patients with minor stroke and intracranial occlusion. Fewer excellent outcomes after intravenous tenecteplase were observed in the disabling deficits group, possibly due to longer times to presentation and thrombolysis for the disabling subgroup.
Abstract 53: Risk of Recurrent Ischemic Stroke Among Patients with Cryptogenic Stroke and Left Ventricular Dysfunction Defined by Left Ventricular Fractional Shortening: A Secondary Analysis of the ARCADIA Trial
Authors: Sharma Richa , Jillella Dinesh , Zhang Cenai , Elkind Mitchell , Kamel Hooman , Di Tullio Marco , Kronmal Richard , Longstreth W , Tirschwell David , Merkler Alexander , Nahab Fadi
Published: January 2025

Background:
Nearly one-quarter of ischemic strokes (IS) in the U.S. are recurrent. The purpose of this study is to determine the risk of recurrent IS associated with left ventricular fractional shortening (LVFS), a measure of LV dysfunction, in patients with cryptogenic stroke and atrial cardiopathy enrolled in the ARCADIA trial.

Methods:
We performed a post-hoc exploratory analysis in the ARCADIA trial, a phase III RCT of 1,015 cryptogenic stroke patients with atrial cardiopathy from February 2018 to February 2023. Those with LV ejection fraction <30% were not eligible. We dichotomized patients by LVFS <25% (reduced) and
>
25% (preserved). We built adjusted Cox proportional hazard models to estimate the hazard ratio (HR) of recurrent IS within each LVFS strata by treatment strategy of apixaban versus aspirin. We evaluated for heterogeneity of treatment effect by LVFS strata, assessing the statistical significance of the interaction term in the model with adjustment for imbalanced covariates.

Results:
The analytic cohort comprised 944 participants, with reduced LVFS in 128 (13.6%) and preserved in 816 (86.4%). Patients with reduced LVFS were significantly more likely to be male (56.2% vs 43.8%, p= 0.009), have higher rates of coronary artery disease (23.4% vs 8.1%, p<0.001) and CHF (18.8% vs 5.2%, p<0.001), higher N-terminal pro-Brain Natriuretic Peptide (median 376 vs 291 pg/mL, p<0.001), lower P-wave terminal force in V1 (median 4063 vs 5225 microVolts x ms, p=0.035), and larger left atrial diameter index (median 2.0 vs 1.9 cm, p=0.028). Recurrent IS occurred in 12 (9.4%) and 57 (7.0%) participants with reduced versus preserved LVFS, respectively. There was an interaction between treatment effect and LVFS strata (p=0.03; Figure). In the adjusted analysis, the risk of recurrent IS among patients with reduced LVFS randomized to apixaban vs aspirin was significantly reduced (HR 0.11, 95% C.I. 0.02-0.61), but there was no treatment effect in patients with preserved LVFS (HR 1.01 95% C.I. 0.59-1.73).

Conclusion:
Apixaban, compared to aspirin, was associated with a reduction in risk of recurrent IS among patients with cryptogenic stroke, atrial cardiopathy, and reduced LVFS. Further study is needed to identify the optimal strategy to prevent recurrent stroke in cryptogenic ischemic stroke patients with LV dysfunction.
Abstract 99: Age and White Matter Injury due to Cerebral Small Vessel Disease are Synergistically Associated with Impaired Neurovascular Coupling.
Authors: Yang Sheng , Webb A/Prof Alastair John
Published: January 2025

Background:
Neurovascular coupling (NVC) depends on cerebral endothelial function, and was impaired in cerebral small vessel disease (CSVD), but previous studies have been small whilst the relationship between NVC and white matter microstructural changes in CSVD remains unclear. This study investigated the association between NVC and both macro- and microstructural white matter changes in the large UK Biobank population.

Methods:
UK Biobank data were used to determine associations between demographics, medical history and structural MRI measures (white matter hyperintensities, WMH; peak width of skeletonized mean diffusivity, PSMD) with NVC. NVC was quantified as the z-score of the fMRI blood-oxygen-level-dependent (BOLD) response to a visual stimulus. WMH volume was calculated from T2-weighted images, normalized to total intracranial volume (ICV), and log-transformed due to skewness. PSMD was derived from diffusion-weighted data. All continuous variables were scaled.

Results:
Among 37,914 participants (mean age: 64.1±7.7 years; 52% female; 1.35% with a history of ischemic stroke), mean PSMD, WMH volume, and NVC were 2.25±0.40x10
–4
mm
2
/s, 0.93±0.01% ICV, and 2.55±1.35, respectively. NVC significantly decreased with age (β=-0.07, p<0.001), hypertension (β=-0.12, p<0.001), diabetes (β=-0.13, p<0.001), and stroke history (β=-0.20, p<0.001).

General linear models demonstrated a significant decrease in NVC associated with higher PSMD (β=-0.03, p<0.001) and WMH (β=-0.04, p<0.001) after controlling for age, sex, hypertension, diabetes, and stroke. Additionally, there was a significant interaction such that the negative impact of PSMD and WMH on NVC was exacerbated by older age (PSMD:
age
β=
-0.04, p<0.01; WMH:
age β=-0.03, p<0.05).

Conclusion:
This study highlights a strong association between impaired NVC and markers of CSVD, including both macrostructural (WMH) and microstructural (PSMD) white matter abnormalities, in a large population. The synergistic exacerbation of these effects by age underscores the potentially critical role of cerebrovascular dysfunction in the development of CSVD.
Abstract DP13: Long-term temporal trends in post-stroke dementia, 2002-2022: A population-wide cohort study
Authors: Joundi Raed , Fang Jiming , Austin Peter , Smith Eric , Yu Amy Y. X. , Hachinski Vladimir , Sposato Luciano , Ganesh Aravind , Sharma Mukul , Kapral Moira
Published: January 2025

Background:
People with stroke are at high risk of dementia. There have been reductions in stroke case fatality and disability but temporal trends in the incidence and absolute burden of post-stroke dementia have not been described.

Methods:
We did a population-wide analysis of over 15 million people in Ontario, Canada between 2002-2022. Using linked administrative databases, we identified all 90-day dementia-free survivors of first acute ischemic stroke or intracerebral hemorrhage (ICH). We evaluated dementia incidence from 90-days after stroke onwards using a validated definition which included hospitalization, physician claims, and dementia medications. We calculated 1-year and 5-year incidence of dementia as percentages and per 100 person-years for each fiscal year, age-/sex-standardized by the 2002 population and with follow-up until March 2022. We stratified incidence trends by sex, stroke type, and severity (90-day home time of <60 days indicating moderate-severe stroke). We described trends in absolute number of people with post-stroke dementia, stratified by sex, and used linear regression to evaluate significance.

Results:
We identified 175,980 people with acute stroke surviving dementia-free to 90 days. From 2002-2021, there was modestly decreasing 1- and 5-year dementia incidence, primarily occurring from 2011 onwards (Figure 1). 5-year dementia decreased by an absolute change of -2.4% (15.5% to 13.1%) and a relative change of -15%. However, there was an increase in the number of people surviving with stroke (Figure 1A-B), so the absolute number of people with post-stroke dementia remained stable or increased over time (Figure 2). Women had higher age-standardized dementia incidence than men, but no difference in trends (Figure 3A-B). There was decreasing dementia incidence for ischemic stroke but no significant change for ICH (Figure 3C-D). Those with 90-day home time <60 days had twice the incidence of dementia compared to those with
>
60 days, with no change over time (Figure 3E-F).

Conclusion:
In this large, population-wide study from 2002-2022, a modest decrease in post-stroke dementia incidence was offset by increasing numbers of stroke survivors and resulted in a rising absolute burden of post-stroke dementia. Those with more severe stroke had 2-fold higher dementia rate which did not change over time despite improvements in stroke care. New strategies are needed to address the persistent and increasing burden of post-stroke dementia.
Abstract DP32: Hypodensity Beyond the Ischemic Core: Penumbral Density Changes Detected with Relative Non-Contrast Computed Tomography
Authors: Vandewalle Lieselotte , Wouters Anke , Christensen Soren , Konduri Praneeta , Yuen Nicole , Mlynash Michael , Seners Pierre , Albers Greg , Demeestere Jelle , Lansberg Maarten , Lemmens Robin
Published: January 2025

Introduction and aims:
Infarcted brain tissue on non-contrast computed tomography (NCCT) causes hypodensity resulting from vasogenic edema. It is unknown if hypoperfusion outside of the ischemic core may result in density changes on NCCT. This study aimed to evaluate the presence of hypodensity in the CT Perfusion (CTP) based penumbra.

Methods:
We included ischemic stroke patients with anterior circulation large vessel occlusions transferred from a primary to a comprehensive stroke center for consideration of thrombectomy from the CRISP2 study. Patients underwent baseline NCCT and CT Perfusion (CTP) at the referring hospital and MRI at the comprehensive center. All images were coregistered to the NCCT. We created relative NCCT (rNCCT) maps on baseline imaging, which is an automated NCCT analysis that compares voxel density to the corresponding area in the contralateral hemisphere. Density alterations on rNCCT were represented as percentages, e.g. -1% represented 1% relative hypodensity compared to the contralateral region. We analyzed relative voxel hypodensity on rNCCT within the core (defined as relative cerebral blood flow <30%) and penumbra (defined as time-to-maximum (Tmax) > 6 seconds minus core lesion volume) (Figure 1). Furthermore, we evaluated the relationship between relative density changes and hypoperfusion severity within the penumbra. To ensure that our findings were restricted to the penumbra, we performed a sensitivity analysis using the diffusion-weighted imaging (DWI) lesion at the receiving hospital to define the ischemic core.

Results:
We included 169 patients with a median penumbra volume of 78 ml (IQR 51-112) and core volume of 1.3 ml (IQR 0-13.3) (Table 1). The median relative voxel hypodensity in the penumbra was 1.8% (p<0.001) and 3.4% in the core (p<0.001). Relative hypodensity in the penumbra was greater with increasing hypoperfusion severity: median 1.5% in areas with Tmax delay between 6 to 8 seconds; median 1.9% in Tmax 8 to 10 seconds; and median 2.2% in Tmax> 10 seconds (p<0.001) (Figure 2). Using the DWI lesion as the core did not alter the results.

Conclusions:
In patients with anterior circulation acute ischemic stroke, we demonstrated relative hypodensity in penumbral tissue on NCCT. The hypodensity was greater in tissue with more severe hypoperfusion. A hypothesis for these findings is edema formation in the penumbra related to hypoperfusion severity. However, its significance remains to be investigated.
Abstract DP35: Enhanced Stroke Detection with Multi-directional Diffusion Weighted Low-field Magnetic Resonance Imaging
Authors: Sorby-Adams Annabel , Pinter Nandor , Kirsch John , Jaikumar Vinay , Goldstein Joshua , Nelson Olivia , Bacchi Stephen , Guo Jennifer , Pitts Johns , Lee Vivien , Muir Keith , Nimjee Shahid , Rosen Matthew , Iglesias Juan Eugenio , Sheth Kevin , Kimberly W. Taylor
Published: January 2025

Introduction:
Portable, low-field (LF) magnetic resonance imaging (MRI) has the potential to improve access to brain imaging and facilitate diagnosis of acute ischemic stroke (AIS). However, due to longer acquisition time, diffusion-weighted imaging (DWI) at LF is often restricted to a single diffusion direction, which may reduce sensitivity of detection. We developed a multi-direction DWI sequence and evaluated its ability to detect stroke lesions compared with a single-direction sequence.

Methods:
Patients with a suspected diagnosis of AIS were prospectively enrolled at three US centers and underwent single-direction
b
0 and
b
900 s/mm
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DWI and generation of corresponding apparent diffusion coefficient (ADC) maps on a 0.064 T MRI (Hyperfine Inc.). A subset of patients underwent additional multi-direction DWI (3 diffusion directions in x, y, and z planes) and generation of trace and ADC maps. Two independent assessors evaluated DWI and ADC scans and recorded the presence or absence of stroke lesions and their location (left/right hemisphere). The agreement, positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity were calculated for both single- and multi-directional images as compared to the ground-truth clinical diagnosis.

Results:
A total of N=66 patients were included, with N=18 undergoing additional multi-directional acquisition. Of these patients, N=36 had a confirmed ischemic stroke, and N=29 had a stroke mimic with no evidence of infarction or diffusion restriction abnormality on conventional high-field imaging. Agreement between assessors regarding lesion detection on single-direction DWI was κ=0.88 and κ=0.84 on ADC, with a κ=0.92 agreement on lesion location. On multi-directional LF-MRI, agreement increased to κ=1.0 for DWI, ADC, and lesion location. Predictive values for detecting AIS on single-direction DWI revealed a PPV of 83.9% and NPV of 71.4% which was associated with a 72.2% sensitivity and 83.3% specificity. NPV, PPV, sensitivity and specificity all increased to 100% when multi-directional DWI was assessed.

Conclusion:
LF single-direction diffusion is sensitive and specific for the detection of acute ischemic infarcts, except for small lesions residing in white matter tracts that align with diffusion gradient direction. A novel LF multi-directional DWI sequence can overcome this limitation and potentially improve qualitative lesion conspicuity. Validation in a larger cohort is warranted.
Abstract DP41: Clinical and Financial Impact of a Home-Based Post-Discharge Care Model: Stroke Mobile
Authors: Batiquin Antonio , Williams Natalee , Sidanmat Harish , Leingang David , Gaines Kenneth , Tarsia Joseph , Mule Todd , Fahimdanesh Kian , Oravetz Philip , Sawyer Robert , Zweifler Richard
Published: January 2025

Introduction&Objective:
Stroke care is fragmented with reported 30-day readmission rates as high as 10-15%. Novel, cost effective strategies to improve care coordination and address social determinants of care are needed. We sought to evaluate the clinical and financial impact of a home-based stroke care delivery model colloquially called Stroke Mobile (SM).

Methods:
Patients discharged to home, home health, rehab or skilled nursing facility followed by home from an Ochsner Health hospital in the New Orleans region between July 2021 through December 2022 with stroke (ischemic stroke, TIA, ICH) and on a value-based contract were eligible for the study. Patients were seen at home by an RN and health educator within 30 days of discharge followed by monthly for 3 consecutive months. Thereafter, patients were seen periodically as determined by the care team up to a year. Patients seen by the SM team were compared to a propensity matched control group comprising of patients eligible for care service by the SM team but not enrolled in the program during the study period. Propensity score matching was performed using age, gender, race and chronic conditions as covariates and “nearest neighbor” algorithm with 1:3 match ratio. Parametric (independent sample t-test) and non-parametric (Wilcoxon rank sum, Chi-square) tests were used to test the difference in overall cost (per member per month (pmpm)), 30-day readmissions, and cost of readmission between groups with an error rate set to <5% (p<0.05).

Results:
Two hundred and seven patients enrolled in SM (intervention group) and 621 eligible patients not enrolled (control group) . $833,760 annual cost savings was observed in the intervention group ($1,226pmpm vs. $1,612pmpm; Δ$386; p<0.05). Of note, significantly higher cost savings were seen within the first 90 days of the program ($764pmpm vs. $1,423pmpm; Δ$659; p<0.05). However, cost savings diminished by the second 90-day interval and plateaued by third and fourth intervals (Fig). No readmissions were observed in the intervention group compared to 2% readmissions with $29pmpm readmission cost in the control group ($0pmpm vs. $29pmpm; p=0.01).

Conclusions:
Our home-based, post-stroke, care delivery program (SM) is effective in reducing the overall costs within the first 180 days of enrollment with maximum benefit noted within the first 90 days. The readmission reduction the SM group did not reach statistical significance, possibly due to a type II error.
Abstract DP5: TNK is Non-Inferior to tPA in Patients Planned to Undergo Endovascular Thrombectomy in Real-World Practice
Authors: Erdenizmenli Mert , Favruzzo Francesco , Saver Jeffrey , Warach Steven , Liebeskind David
Published: January 2025

Introduction:
Outcomes after thrombolysis with alteplase (tPA) versus tenecteplase (TNK) prior to endovascular thrombectomy (EVT) have not been directly compared in real-world data (RWD). We leveraged systematic analysis for RWD from 2 major academic stroke centers that solely used tPA or TNK prior to EVT over a 4-year period to determine potential differences in recanalization, reperfusion and clinical outcomes.

Methods:
A retrospective, cohort, multicenter study was conducted to investigate outcomes for patients with large vessel occlusions receiving either tPA+EVT or TNK+EVT. tPA was used exclusively for thrombolysis at one center (n=74), while TNK was used exclusively for thrombolysis at another center (n=130). The primary outcome that was measured was functional independence (defined by a modified Rankin score of 0-1) at discharge. Secondary outcomes that were measured include good functional outcomes (defined by a modified Rankin score of 0-2) at discharge and early neurologic improvement (ENI; defined as an improvement in NIH scores by 8 or more in a 24 hour time period). Safety outcomes included symptomatic intracranial hemorrhage (sICH; defined as a worsening of NIH scores by 4 or more with concurrent PH-2 hemorrhagic transformation in a 24 hour time period), any hemorrhagic transformation (HT), and all-cause mortality by discharge.

Results:
The rate of functional independence was 25.7% for the tPA+EVT group and 33.8% for the TNK+EVT group (p-value 0.291; RR 1.32 [95% CI 0.55, 3.14]). The rate of good functional outcomes was 35.1% vs 37.7% (p-value 0.831; RR 1.07 [95% CI 0.57, 2.02]). The rate of ENI was 50.0% vs 47.7% (p-value 0.864; RR 0.95 [95% CI 0.63, 1.44]). The rate of sICH was 2.7% vs 0.8% (p-value 0.298; RR 3.51 [95% CI 0.32, 38.1]). The rate of any HT was 32.4% vs 38.4% (p-value 0.45; RR 0.84 [95% CI 0.57, 1.25]). The rate of all cause mortality was 6.8% vs 6.9% (p-value 1.0; RR 0.98 [95% CI 0.34, 2.80]).

Conclusions:
Real-world evidence on tPA versus TNK prior to EVT reveals potential equivalence in outcomes after acute ischemic stroke. Detailed analyses (site of arterial occlusion, recanalization and reperfusion effectiveness, and transfer times between hospitals) will be conducted to determine if there are practical advantages in utilizing one thrombolytic over another as an adjunct to EVT in patients with large vessel occlusions in real-world practice.
Abstract DP52: Adherence to Physical Activity Recommendations among Stroke Survivors in the United States
Authors: Vemuri Ajith , hejazian Sina , Vafaei Sadr Alireza , Zhou Shouhao , Decker Keith , Hakun Jonathan , Sciamanna Christopher , Abedi Vida , Zand Ramin
Published: January 2025

Background:
Physical activity is an effective modifiable behavior for preventing recurrent strokes. This study aims to determine the adherence to physical activity recommendations among stroke survivors in the United States. We further compared our findings with the adherence observed among myocardial infarction (MI) survivors.

Methods:
We utilized data from the 2011-2019 Behavioral Risk Factor Surveillance System, a nationally representative survey. To establish benchmarks, we referenced the physical activity recommendations outlined in 2011, 2014, and 2021 American Heart Association stroke prevention guidelines. Adherence to recommendations was determined by the respondents' self-reported intensity, duration, and frequency of physical activity. Multivariate logistic regression was used to compare adherence in stroke survivors, MI survivors, and healthy adults.

Results:
Among 48,222 stroke survivors in the United States, the overall adherence rates to 2011, 2014, and 2021 physical activity guidelines were 75.4%, 40.2%, and 69.2%. For independently mobile stroke survivors, the adherence rates increased to 78.1%, 42.1%, and 69.9%. When 2021 recommendations were used as a benchmark, older (≥65) stroke survivors were more likely to adhere to recommendations than younger survivors (71.9%vs.62.3%; p<0.0001). However, when the benchmark was changed to the 2011 and 2014 guidelines, which recommended longer exercise durations, the difference between younger and older stroke survivors dissipated. After adjusting for sociodemographic factors and comorbidities, non-Hispanic Black survivors were less likely to adhere to recommendations (aOR,0.81[95%CI,0.7–0.94]), whereas older and higher educated stroke survivors were more likely to adhere to recommendations. Geographically, stroke belt and non-rural residents were less likely to adhere to recommendations [(63.5%vs.67.9%;p<0.0001), (53.8%vs.58.7%;p<0.0001)]. Stroke and MI survivors were less likely to adhere to the latest recommendations than healthy adults (aOR,0.74[95%CI,0.69-0.8], (aOR,0.24[95%CI,0.22-0.26])).

Conclusion:
A substantial number of stroke survivors do not meet physical activity recommendations. Tailored interventions should be designed for at-risk populations, e.g., non-Hispanic Black survivors and lower educated stroke survivors.
Abstract DP60: Molecular Mechanisms of Cerebral Microhemorrhage Formation in Chronic Kidney Disease
Authors: Hung Yu-Han , Fang Chuo , Lau Wei Ling , Lee Donghy , Xie Danny , Liu Jihua , Liu Han , Wu Jie , Paganini-Hill Annlia , Cribbs David , Choi Bernard , Fisher Mark
Published: January 2025

Background:
Chronic kidney disease (CKD) has emerged as an independent risk factor for cerebral microhemorrhages (CMH). We examined molecular mechanisms of CMH formation in mouse models of CKD and hypertension (HTN) using RNA transcriptomics and mTOR complex 1 (mTORC1) inhibition.

Methods:
Aged (17-month-old) mice were treated with either 0.2% adenine diet to induce CKD, or angiotensin II (ATII) via subcutaneous osmotic pumps to induce HTN and compared with control mice. A subset of CKD mice was treated with rapamycin to inhibit mTORC1 signaling. After 4 weeks, RNA sequencing of mouse brain was done via Illumina NovaSeq 6000 with downstream analysis using Hisat2, Salmon, and DESeq2. Differentially expressed genes (DEGs) and enriched pathways were identified using the MsigDB Hallmark 2020 database. Pathway analysis was further examined using qPCR and immunohistochemistry staining. CMH were quantified using Prussian blue histology.

Results:
CKD mice had increased CMH number (1.12±0.10 vs 0.85±0.08 per cm
2
in CKD vs control mice, p<0.05), and whole brain RNA-seq showed significant alterations in the mTORC1 pathway, a critical regulator for cell growth and metabolism. Specifically, 18 DEGs were involved in mTORC1 signaling in CKD compared with control animals. qPCR and immunohistochemistry analysis confirmed CKD-associated upregulation of DNA damage-induced transcript 4 (DDIT4), an upstream component of the mTORC1 pathway. ATII-induced HTN more than doubled CMH formation (1.44±0.47 vs. 0.60±0.66 per cm
2
in HTN vs. control mice, p< 0.01), without significant alteration of the mTORC1 pathway. Treatment of CKD mice with the mTOR inhibitor rapamycin significantly reduced CMH burden (24% reduction in CMH number, p<0.05 and 56% reduction in CMH area, p<0.01).

Conclusions:
Cerebral microhemorrhages were increased in both the CKD and HTN models. However, alteration of brain mTORC1 pathway was observed only in CKD animals, suggesting a specific molecular signature in the CKD brain. Our study supports mTORC1 inhibition as a novel approach to inhibit cerebral microhemorrhage formation in CKD.