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Introduction: We assess the risk of stroke in individuals with and without a migraine diagnosis, adjusting for demographic variables and stroke risk factors using participant information from the All of Us database. Method: Diagnoses of migraine, stroke and comorbidities were identified using ICD9 and ICD10 codes. A multivariable logistic regression analysis was performed to assess the association between migraine and risk of stroke adjusting for comorbidities including hypertension, atrial fibrillation, hyperlipidemia, diabetes, tobacco use, depression and demographics (age, sex at birth, race and ethnicity). To compare the prevalence of stroke between individuals with and without migraine, odds ratios using a 95% confidence interval (CI) were calculated. Results: Within the All of Us database, 31,444 individuals received a migraine diagnosis (female=25,374/81%, male=5,391/17%, other=679/2%; mean (std) age=54.9 (15.6)) and 379,283 did not have a migraine diagnosis (female=222,104/59%, male=149,182/39%, other=7,997/2%; mean (SD) age=55.9 (17.2)), see Figure 1 for detailed demographics. The migraine cohort had a greater proportion of women (81% vs 59%, p<0.001), a higher proportion of white individuals (61% vs. 55%, p<0.001) fewer African American individuals (15% vs. 19%, p<0.001) and a lower proportion of individuals who were 61 or older (39% vs 45%, p<0.001) compared to the non-migraine cohort. Compared to the non-migraine cohort, individuals with migraine had significantly higher rates of comorbidities, including depression (13% vs. 4%, p<0.001), diabetes (16% vs. 7%), tobacco use (23% vs. 9%, p<0.001), hyperlipidemia (48% vs. 22%, p<0.001), hypertension (57% vs. 27%, p<0.001), and atrial fibrillation (7% vs. 4%, p<0.001). A multivariate regression model adjusted for differences between cohort demographics and comorbidities found that individuals with migraine had 2.14 higher odds of overall stroke compared to the non-migraine cohort (OR 2.14, 95% CI [ 2.04, 2.24]. Discussion: After adjusting for cohort imbalances in demographics and comorbidities, individuals with migraine had a 2.14 times higher risk of stroke compared to those without a migraine diagnosis. Our analysis, using data from the All of Us database, confirms previous findings and suggests that while comorbidities are more prevalent in those with migraine, they do not fully account for the increased stroke risk.

ImportanceAtrial fibrillation (AF) is the most common, chronic, cardiac arrythmia in older US adults. It is not known whether AF is independently associated with increased risk of retinal stroke (central retinal artery occlusion), a subtype of ischemic stroke that causes severely disabling visual loss in most cases and is a harbinger of further vascular events.ObjectiveTo determine whether there is an association between AF and retinal stroke.Design, Setting, and ParticipantsThis retrospective cohort study was performed between July 2023 and May 2024 using computerized inpatient, outpatient, emergency department, and skilled nursing facility claims files for a 5% sample of US fee-for-service Medicare beneficiaries aged 66 years and older between 2000 and 2020. Follow-up ended at death, conclusion of fee-for-service Medicare coverage, end of the study period, or loss to follow-up of 85% of the study cohort.ExposureAF, based on validated International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes.Main Outcomes and MeasuresThe primary end point was incident retinal stroke in the primary diagnostic position of a single claim in any venue of care. Secondary end points included retinal stroke in any position of a single claim, 1 positive control end point (cerebral ischemic stroke), and 4 negative control end points (central retinal vein occlusion, urinary tract infection, humeral fracture, and cataract). Unadjusted and adjusted hazard ratios (HRs) and rate differences were computed across matched and overlap-weighted cohorts with and without AF (defined as 1 inpatient claim or 2 outpatient claims within a 365-day period).ResultsIn total, 1 090 144 patients (591 400 female [54.3%]; mean [SD] age, 76.92 [7.09] years) were included in the study; 545 072 patients had AF and 545 072 were matched controls. The median (IQR) follow-up was 45 (18 to 90) months. In total, 1333 patients with AF (rate, 0.55 per 1000 person-years) and 1082 AF-free matched controls (rate, 0.50 per 1000 person-years) experienced retinal stroke. The cause-specific, adjusted HR of retinal stroke after overlap weighting was 1.14 (95% CI, 1.02 to 1.28; adjusted rate difference, 0.05 [95% CI, −0.01 to 0.11]). AF was associated with cerebral ischemic stroke (adjusted HR, 1.73 [95% CI, 1.69 to 1.76]; adjusted rate difference, 10.11 [95% CI, 9.72 to 10.49]). Of 4 prespecified negative control end points, AF was not associated with central retinal vein occlusion but was associated with urinary tract infection, cataract, and humeral fracture.Conclusions and RelevanceIn this cohort study of Medicare beneficiaries aged 66 years and older, AF was independently associated with retinal stroke. The magnitude of the association was small, and a contribution from residual, unmeasured confounding could not be excluded.

AbstractBackgroundWomen with suspected coronary microvascular dysfunction (CMD) may be at higher risk of experiencing cognitive decline due to cerebral small vessel disease, a known contributor to Alzheimer’s disease and related dementias (ADRD). A potential underlying mechanism that could accelerate this cognitive decline is the accumulation of brain tissue iron, which has been previously linked to changes in brain function potentially caused by oxidative stress and cell death. Therefore, we aim to elucidate whether a similar mechanism could affect women with suspected CMD by investigating the potential role of iron deposition on the brain’s functional organization and its effect on cognition using advanced magnetic resonance imaging (MRI).Material and MethodsTwenty‐seven women with suspected CMD [Age; median (range) = 54 (29‐76)], drawn from ongoing cohorts (3R01HL146158‐04S1,3U54AG065141‐04S1), underwent a 3T MRI protocol, including submillimeter T2* 3‐dimensional echo‐planar‐imaging for assessing iron deposition with high‐resolution quantitative susceptibility mapping (QSM) and resting‐state fMRI (rs‐fMRI). Iron content was quantified by total‐generalized‐variation based QSM analysis. Functional integrity was determined via graph theoretical approach (i.e., nodal degree). Cognitive assessment was also performed using the NIH Toolbox. Mediation analysis was conducted using Python Statsmodels.ResultsMost of the women with suspected CMD showed lower performance in processing speed, working memory, executive function, and attention (Figure 1A). We found a significant association between elevated iron levels in paracentral gyrus and lower functional connectivity in left hippocampus (p=0.005, adjusted‐r2=0.19) (Figure 1B). Elevated iron level in the paracentral gyrus showed an impact on cognitive performance in the domains of executive function and attention (p<0.0001, coefficient=531.09) as well as language functions and crystalized abilities (p=0.036, coefficient=362.45), mediated by functional connectivity in the left hippocampus (indirect effect on executive function / language: p = 0.034 / 0.038, coefficient = ‐254.54 /‐ 213.06) (Figure 1C).ConclusionsOur results suggest that changes in hippocampal functional organization are associated with cortical iron deposition and mediate its impact on cognitive performances. These changes may increase the risk of cognitive decline/ADRD or in women with suspected CMD. Future research in a larger cohort with a longitudinal design is necessary to validate and expand upon these findings.

AbstractBackgroundScanning laser ophthalmoscopy (SLO) visualizes two important markers of cognitive dysfunction in the retina: vascular changes and amyloid plaque (AP) deposition. The relationship between retinal arteriolar versus venular changes and perivascular amyloid deposition across the continuum of neurodegeneration is imperfectly understood. We investigate the retinal perivascular AP distribution in relationship to cognitive and neuroimaging measures in a cohort of cognitively normal and impaired individuals.Method34 subjects with normal or impaired cognition underwent retinal SLO, brain magnetic resonance imaging and standard neuropsychometric testing. Retinal peri‐arteriolar and peri‐venular curcumin positive AP were quantified in the supero‐temporal retinal quadrant, in the first, second and third‐order retinal vascular branches. The peri‐venular and peri‐arteriolar AP count were compared between patients with normal and impaired cognition, and their correlation with brain volumes, white matter hyperintensities and cognitive Z‐scores was determined.ResultWe analyzed retinal para‐venous and para‐arteriolar amyloid count in 28 subjects, mean (SD) age 65 (7.3), 50% female, 19 (52.6%) with impaired cognition. Para‐arteriolar plaque count was higher than peri‐venular plaque in the entire cohort (p<0.0001). Secondary branch peri‐venular amyloid plaque count was higher in patients with MOCA ≤26. Tertiary branch perivascular AP count significantly and negatively correlated with hippocampal volume and positively correlated white matter hyperintensity lesion count.ConclusionRetinal AP deposit peri‐arteriolarly overall and peri‐venularly in the secondary branches in cognitively impaired. Perivascular amyloid burden in small retinal branches correlates with hippocampal volume and white matter hyperintensities.

AbstractBackgroundWomen with suspected coronary microvascular dysfunction (CMD) may be at higher risk of experiencing cognitive decline due to cerebral small vessel disease, a known contributor to Alzheimer’s disease and related dementias (ADRD). A potential underlying mechanism that could accelerate this cognitive decline is the accumulation of brain tissue iron, which has been previously linked to changes in brain function potentially caused by oxidative stress and cell death. Therefore, we aim to elucidate whether a similar mechanism could affect women with suspected CMD by investigating the potential role of iron deposition on the brain’s functional organization and its effect on cognition using advanced magnetic resonance imaging (MRI).Material and MethodsTwenty‐seven women with suspected CMD [Age; median (range) = 54 (29‐76)], drawn from ongoing cohorts (3R01HL146158‐04S1,3U54AG065141‐04S1), underwent a 3T MRI protocol, including submillimeter T2* 3‐dimensional echo‐planar‐imaging for assessing iron deposition with high‐resolution quantitative susceptibility mapping (QSM) and resting‐state fMRI (rs‐fMRI). Iron content was quantified by total‐generalized‐variation based QSM analysis. Functional integrity was determined via graph theoretical approach (i.e., nodal degree). Cognitive assessment was also performed using the NIH Toolbox. Mediation analysis was conducted using Python Statsmodels.ResultsMost of the women with suspected CMD showed lower performance in processing speed, working memory, executive function, and attention (Figure‐1A). We found a significant association between elevated iron levels in paracentral gyrus and lower functional connectivity in left hippocampus (p = 0.005, adjusted‐r2 = 0.19) (Figure‐1B). Elevated iron level in the paracentral gyrus showed an impact on cognitive performance in the domains of executive function and attention (p<0.0001, coefficient = 531.09) as well as language functions and crystalized abilities (p = 0.036, coefficient = 362.45), mediated by functional connectivity in the left hippocampus (indirect effect on executive function / language: p = 0.034 / 0.038, coefficient = ‐254.54 /‐ 213.06) (Figure‐1C).ConclusionsOur results suggest that changes in hippocampal functional organization are associated with cortical iron deposition and mediate its impact on cognitive performances. These changes may increase the risk of cognitive decline/ADRD or in women with suspected CMD. Future research in a larger cohort with a longitudinal design is necessary to validate and expand upon these findings.

Objective To determine the frequency and accuracy of diffusion restriction (DR) of the retina and/or optic nerve (ON) detection on standard brain magnetic resonance diffusion-weighted imaging (DWI-MRI) in patients presenting with acute non-arteritic central retinal artery occlusion (CRAO). Methods This is a retrospective case-control study that includes all consecutive patients presenting to our tertiary academic center from 2013-2021 with acute non-arteritic CRAO (cases) or acute ischemic stroke syndrome (controls, age and gender-matched) that had brain MRI performed within 14 days from symptom onset. Two neurology residents (junior and senior), a vascular neurologist, and two neuroradiologists, blinded to the site of CRAO, independently reviewed the brain MRIs to assess for the presence of retina and ON DR. The consensus agreement between the two neuroradiologists was used to perform sensitivity and specificity analyses and calculate inter-rater reliability (prevalence-adjusted bias-adjusted kappa coefficient). Results A total of 128 patients with acute non-arteritic CRAO (mean (SD) age 69 (14) years; 50% female; median time from CRAO to DW-MRI 2 days (IQR 1-5)) and 128 age and gender-matched controls with acute cerebral ischemia were included. After the neuroradiologist consensus, DR was correctly identified in the retina or ON in 51/128 (39.8%) CRAO cases, retina alone 27.3%, ON alone 24.2%, and both retina and ON 11.7%, with almost perfect neuroradiologists’ inter-rater reliability for retina (K = 0.91) and ON (K = 0.83). Among controls, the retina DR was identified in 1/128 (0.8%) and ON DR in 5/128 (3.9%). The sensitivity, specificity, positive predictive value, and negative predictive value were 28.1%, 99.2%, 97.3%, and 58.0% for retina DR, and 27.3%, 96.1%, 87.5%, and 56.9% for ON DR. Conclusions Though experienced neuroradiologists identified retina and ON DR with excellent inter-rater reliability, these are infrequent findings in real world CRAO practice, with excellent specificity but limited sensitivity. Prospective studies with larger cohort of patients, optimization of standardized orbit DWI-MRI protocols are needed to facilitate a more accurate and reliable identification of retina and ON DR in acute CRAO.

Background: Although no tests are currently available to predict post-stroke depression (PSD), a risk factor for diminished quality of life and stroke-related death, emerging evidence suggests that ischemic stroke (IS) may induce behavioral changes by damaging connections throughout the brain rather than via localized injury. Hypothesis: We sought to determine if active (surveys) and passive (accelerometer, GPS, and other sensors) smartphone data could quantify exploratory behavioral proxies of PSD. Methods: Thirty-four adults with a recent IS (n = 12) or transient ischemic attack (TIA) (n = 22) diagnosis were followed for 3 months. Participants used the Beiwe app to complete a weekly Patient Health Questionnaire-8 (PHQ-8) survey and were evaluated every 30 days with the Montgomery-Asberg Depression Rating Scale (MADRS). Results: Preliminary analysis of app survey compliance was adequate (86%), and the quantity of data collected was greater for Android than iOS phones. PHQ-8 indicated depression (moderate or severe) in 20% of participants. MADRS highly correlated with the most recent PHQ-8 ( r = 0.92, 95% CI (0.19, 0.99), P = 0.028). Several exploratory passive physical activity and social measures showed statistically significant change over time and/or associations with PHQ-8 and MADRS. Conclusion: Low-burden smartphone data holds promise for developing novel IS and TIA outcome measures as well as identifying patients most at risk of PSD.

Telemedicine for stroke (Telestroke) has been a key component to efficient, widespread acute stroke care for many years. The expansion of reimbursement through the Furthering Access to Stroke Telemedicine Act and rapid deployment of telemedicine resources during the COVID-19 public health emergency have further expanded remote care, with practitioners of varying educational backgrounds, and experience providing acute stroke care via telemedicine (Telestroke). Some Telestroke practitioners have not had fellowship-level vascular neurology training and many are without training specific to virtual modalities. While many vascular neurology fellowship programs incorporate Telestroke training into the curriculum, components of this curriculum are not consistent, extent of involvement is variable, and not all fellows receive hands-on training in remote care. Furthermore, the extent of training and evaluation of Telestroke in American Board of Psychiatry and Neurology training requirements and Accreditation Council for Graduate Medical Education assessments for vascular neurology fellowship are not standardized. We suggest that Telestroke be formally incorporated into vascular neurology fellowship curricula and provide considerations for key components of this training and metrics for evaluation.