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1. HeadCT-ONE: Enabling Granular and Controllable Automated Evaluation of Head CT Radiology Report Generation

Author

Acosta, Julián N., Zhang, Xiaoman, Dogra, Siddhant, Zhou, Hong-Yu, Payabvash, Seyedmehdi, Falcone, Guido J., Oermann, Eric K., and Rajpurkar, Pranav

Subjects
Computer Science - Artificial Intelligence
Abstract

We present Head CT Ontology Normalized Evaluation (HeadCT-ONE), a metric for evaluating head CT report generation through ontology-normalized entity and relation extraction. HeadCT-ONE enhances current information extraction derived metrics (such as RadGraph F1) by implementing entity normalization through domain-specific ontologies, addressing radiological language variability. HeadCT-ONE compares normalized entities and relations, allowing for controllable weighting of different entity types or specific entities. Through experiments on head CT reports from three health systems, we show that HeadCT-ONE's normalization and weighting approach improves the capture of semantically equivalent reports, better distinguishes between normal and abnormal reports, and aligns with radiologists' assessment of clinically significant errors, while offering flexibility to prioritize specific aspects of report content. Our results demonstrate how HeadCT-ONE enables more flexible, controllable, and granular automated evaluation of head CT reports.

Published
2024

9. Lifetime and Acute Stress Predict Functional Outcomes Following Stroke: Findings From the Longitudinal STRONG Study

Author

Holman, E. Alison, Cramer, Steven C., Shah, Shreyansh, Griessenauer, Christoph J., Patel, Nirav, Lin, David J., Gee, Joey, Moon, Johnson, Schwertfeger, Julie, Jayaraman, Arun, Lee, Robert, Lansberg, Maarten, Payne, Jeremy, Patten, Carolynn, Agrawal, Kunal, DeJong, Stacey, Cole, John, Silver, Brian, Cucchiara, Brett, Busza, Ania, Liew, Sook-Lei, Alderman, Susan, Hayes, Heather, Majersik, Jennifer J., Worrall, Brad, Tirschwell, David, Bushnell, Cheryl, El Husseini, Nada, Lee, Jin-Moo, and Falcone, Guido J.

Published
2023
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10. Detection of Intracerebral Hemorrhage Using Low-Field, Portable Magnetic Resonance Imaging in Patients With Stroke

Author

Mazurek, Mercy H., Parasuram, Nethra R., Peng, Teng J., Beekman, Rachel, Yadlapalli, Vineetha, Sorby-Adams, Annabel J., Lalwani, Dheeraj, Zabinska, Julia, Gilmore, Emily J., Petersen, Nils H., Falcone, Guido J., Sujijantarat, Nanthiya, Matouk, Charles, Payabvash, Sam, Sze, Gordon, Schiff, Steven J., Iglesias, Juan Eugenio, Rosen, Matthew S., de Havenon, Adam, Kimberly, W. Taylor, and Sheth, Kevin N.

Published
2023
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11. Direct carotid puncture for mechanical thrombectomy in acute ischemic stroke patients with prohibitive vascular access.

Author

Cord, Branden J, Kodali, Sreeja, Strander, Sumita, Silverman, Andrew, Wang, Anson, Chouairi, Fouad, Koo, Andrew B, Nguyen, Cindy Khanh, Peshwe, Krithika, Kimmel, Alexandra, Porto, Carl M, Hebert, Ryan M, Falcone, Guido J, Sheth, Kevin N, Sansing, Lauren H, Schindler, Joseph L, Matouk, Charles C, and Petersen, Nils H

Subjects
acute ischemic stroke, difficult vascular access, direct carotid puncture, large-vessel occlusion, mechanical thrombectomy, vascular disorders, Brain Disorders, Neurosciences, Clinical Research, Stroke, Cardiovascular, Good Health and Well Being, Clinical Sciences, Neurology & Neurosurgery
Abstract

ObjectiveWhile the benefit of mechanical thrombectomy (MT) for patients with anterior circulation acute ischemic stroke with large-vessel occlusion (AIS-LVO) has been clearly established, difficult vascular access may make the intervention impossible or unduly prolonged. In this study, the authors evaluated safety as well as radiographic and functional outcomes in stroke patients treated with MT via direct carotid puncture (DCP) for prohibitive vascular access.MethodsThe authors retrospectively studied patients from their prospective AIS-LVO database who underwent attempted MT between 2015 and 2018. Patients with prohibitive vascular access were divided into two groups: 1) aborted MT (abMT) after failed transfemoral access and 2) attempted MT via DCP. Functional outcome was assessed using the modified Rankin Scale at 3 months. Associations with outcome were analyzed using ordinal logistic regression.ResultsOf 352 consecutive patients with anterior circulation AIS-LVO who underwent attempted MT, 37 patients (10.5%) were deemed to have prohibitive vascular access (mean age [± SD] 82 ± 11 years, mean National Institutes of Health Stroke Scale [NIHSS] score 17 ± 5, with females accounting for 75% of the patients). There were 20 patients in the DCP group and 17 in the abMT group. The two groups were well matched for the known predictors of clinical outcome: age, sex, and admission NIHSS score. Direct carotid access was successfully obtained in 19 of 20 patients. Successful reperfusion (thrombolysis in cerebral infarction score 2b or 3) was achieved in 16 (84%) of 19 patients in the DCP group. Carotid access complications included an inability to catheterize the carotid artery in 1 patient, neck hematomas in 4 patients, non-flow-limiting common carotid artery (CCA) dissections in 2 patients, and a delayed, fatal carotid blowout in 1 patient. The neck hematomas and non-flow-limiting CCA dissections did not require any subsequent interventions and remained clinically silent. Compared with the abMT group, patients in the DCP group had smaller infarct volumes (11 vs 48 ml, p = 0.04), a greater reduction in NIHSS score (-4 vs +2.9, p = 0.03), and better functional outcome (shift analysis for 3-month modified Rankin Scale score: adjusted OR 5.2, 95% CI 1.02-24.5; p = 0.048).ConclusionsDCP for emergency MT in patients with anterior circulation AIS-LVO and prohibitive vascular access is safe and effective and is associated with higher recanalization rates, smaller infarct volumes, and improved functional outcome compared with patients with abMT after failed transfemoral access. DCP should be considered in this patient population.

Published
2020

12. Fixed Compared With Autoregulation-Oriented Blood Pressure Thresholds After Mechanical Thrombectomy for Ischemic Stroke.

Author

Petersen, Nils H, Silverman, Andrew, Strander, Sumita M, Kodali, Sreeja, Wang, Anson, Sansing, Lauren H, Schindler, Joseph L, Falcone, Guido J, Gilmore, Emily J, Jasne, Adam S, Cord, Branden, Hebert, Ryan M, Johnson, Michele, Matouk, Charles C, and Sheth, Kevin N

Subjects
Humans, Brain Ischemia, Thrombectomy, Prospective Studies, Homeostasis, Blood Pressure, Cerebrovascular Circulation, Models, Cardiovascular, Aged, Aged, 80 and over, Middle Aged, Female, Male, Stroke, arterial pressure, blood pressure, brain, hemorrhage, thrombectomy, Neurosciences, Clinical Research, Hypertension, Brain Disorders, Cardiovascular, Good Health and Well Being, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and Purpose- Loss of cerebral autoregulation in the acute phase of ischemic stroke leaves patients vulnerable to blood pressure (BP) changes. Effective BP management after endovascular thrombectomy may protect the brain from hypoperfusion or hyperperfusion. In this observational study, we compared personalized, autoregulation-based BP targets to static systolic BP thresholds. Methods- We prospectively enrolled 90 patients undergoing endovascular thrombectomy for stroke. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure. The resulting autoregulatory index was used to trend the BP range at which autoregulation was most preserved. Percent time that mean arterial pressure exceeded the upper limit of autoregulation or decreased below the lower limit of autoregulation was calculated for each patient. Time above fixed systolic BP thresholds was computed in a similar fashion. Functional outcome was measured with the modified Rankin Scale at 90 days. Results- Personalized limits of autoregulation were successfully computed in all 90 patients (age 71.6±16.2, 47% female, mean National Institutes of Health Stroke Scale 13.9±5.7, monitoring time 28.0±18.4 hours). Percent time with mean arterial pressure above the upper limit of autoregulation associated with worse 90-day outcomes (odds ratio per 10% 1.84 [95% CI, 1.3-2.7] P=0.002), and patients with hemorrhagic transformation spent more time above the upper limit of autoregulation (10.9% versus 16.0%, P=0.042). Although there appeared to be a nonsignificant trend towards worse outcome with increasing time above systolic BP thresholds of 140 mm Hg and 160 mm Hg, the effect sizes were smaller compared with the personalized approach. Conclusions- Noninvasive determination of personalized BP thresholds for stroke patients is feasible. Deviation from these limits may increase risk of further brain injury and poor functional outcome. This approach may present a better strategy compared with the classical approach of maintaining systolic BP below a predetermined value, though a randomized trial is needed to determine the optimal approach for hemodynamic management.

Published
2020

13. Emergent external ventricular drain placement in patients with factor Xa inhibitor-associated intracerebral hemorrhage after reversal with andexanet alfa

Author

Ammar, Abdalla A., Elsamadicy, Aladine A., Ammar, Mahmoud A., Reeves, Benjamin C., Koo, Andrew B., Falcone, Guido J., Hwang, David Y., Petersen, Nils, Kim, Jennifer A., Beekman, Rachel, Prust, Morgan, Magid-Bernstein, Jessica, Acosta, Julián N., Herbert, Ryan, Sheth, Kevin N., Matouk, Charles C., and Gilmore, Emily J.

Published
2023
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19. Decreases in Blood Pressure During Thrombectomy Are Associated With Larger Infarct Volumes and Worse Functional Outcome.

Author

Petersen, Nils H, Ortega-Gutierrez, Santiago, Wang, Anson, Lopez, Gloria V, Strander, Sumita, Kodali, Sreeja, Silverman, Andrew, Zheng-Lin, Binbin, Dandapat, Sudeepta, Sansing, Lauren H, Schindler, Joseph L, Falcone, Guido J, Gilmore, Emily J, Amin, Hardik, Cord, Branden, Hebert, Ryan M, Matouk, Charles, and Sheth, Kevin N

Subjects
Humans, Brain Ischemia, Cerebral Infarction, Disease Progression, Magnetic Resonance Imaging, Treatment Outcome, Thrombectomy, Retrospective Studies, Recovery of Function, Blood Pressure, Aged, Aged, 80 and over, Middle Aged, Female, Male, Stroke, Arterial Pressure, blood pressure, brain ischemia, hypotension, reperfusion, thrombectomy, Clinical Research, Biomedical Imaging, Neurosciences, Brain Disorders, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and Purpose- After large-vessel intracranial occlusion, the fate of the ischemic penumbra, and ultimately final infarct volume, largely depends on tissue perfusion. In this study, we evaluated whether blood pressure reduction and sustained relative hypotension during endovascular thrombectomy are associated with infarct progression and functional outcome. Methods- We identified consecutive patients with large-vessel intracranial occlusion ischemic stroke who underwent mechanical thrombectomy at 2 comprehensive stroke centers. Intraprocedural mean arterial pressure (MAP) was monitored throughout the procedure. ΔMAP was calculated as the difference between admission MAP and lowest MAP during endovascular thrombectomy until recanalization. Sustained hypotension was measured as the area between admission MAP and continuous measurements of intraprocedural MAP (aMAP). Final infarct volume was measured using magnetic resonance imaging at 24 hours, and functional outcome was assessed using the modified Rankin Scale at discharge and 90 days. Associations with outcome were analyzed using linear and ordinal multivariable logistic regression. Results- Three hundred ninety patients (mean age 71±14 years, mean National Institutes of Health Stroke Scale score of 17) were included in the study; of these, 280 (72%) achieved Thrombolysis in Cerebral Infarction 2B/3 reperfusion. Eighty-seven percent of patients experienced MAP reductions during endovascular thrombectomy (mean 31±20 mm Hg). ΔMAP was associated with greater infarct growth ( P=0.036) and final infarct volume ( P=0.035). Mean ΔMAP among patients with favorable outcomes (modified Rankin Scale score, 0-2) was 20±21 mm Hg compared with 30±24 mm Hg among patients with poor outcome ( P=0.002). In the multivariable analysis, ΔMAP was independently associated with higher (worse) modified Rankin Scale scores at discharge (adjusted odds ratio per 10 mm Hg, 1.17; 95% CI, 1.04-1.32; P=0.009) and at 90 days (adjusted odds ratio per 10 mm Hg, 1.22; 95% CI, 1.07-1.38; P=0.003). The association between aMAP and outcome was also significant at discharge ( P=0.002) and 90 days ( P=0.001). Conclusions- Blood pressure reduction before recanalization is associated with larger infarct volumes and worse functional outcomes for patients affected by large-vessel intracranial occlusion stroke. These results underscore the importance of BP management during endovascular thrombectomy and highlight the need for further investigation of blood pressure management after large-vessel intracranial occlusion stroke.

Published
2019

21. Multi‐phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author

Temprano‐Sagrera, Gerard, Sitlani, Colleen M., Bone, William P., Martin‐Bornez, Miguel, Voight, Benjamin F., Morrison, Alanna C., Damrauer, Scott M., de Vries, Paul S., Smith, Nicholas L., Sabater‐Lleal, Maria, Dehghan, Abbas, Heath, Adam S, Morrison, Alanna C, Reiner, Alex P, Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M, Hayward, Caroline, Ward‐Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P, Tregouet, David A, Mook‐Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W, Leebeek, Frank W.G., Rosendaal, Frits R, Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A, Bressler, Jan, Huffman, Jennifer E, Rotter, Jerome I, Yao, Jie, Wilson, James F, Bis, Joshua C, Hahn, Julie M, Desch, Karl C, Wiggins, Kerri L, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Liu, Melissa, Brown, Michael R, Conomos, Matthew P, Jhun, Min‐A, Chen, Ming‐Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L, Peyser, Patricia A, Elliot, Paul, de Vries, Paul S, Wei, Peng, Wild, Philipp S, Morange, Pierre E, van der Harst, Pim, Yang, Qiong, Le, Ngoc‐Quynh, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M, Cox, Simon R, Trompet, Stella, Felix, Stephan B, Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, Guo, Xiuqing, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Jackson, Rabecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, Frazer, Kelly A, McCauley, Bryan M, Taylor, Kent, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean‐François, O’Donnell, Chris J, Kim, Jihye, Kraft, Peter, Hansen, John‐Bjarne, Heit, John A, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M, Morange, Pierre‐Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, Trégouët, David‐Alexandre, Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten‐Jacobs, Loes, Giese, Anne‐Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chen, Wei‐Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Holliday, Elizabeth G, Howard, George, Hsu, Fang‐Chi, Hyacinth, Hyacinth I, Arfan Ikram, M, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez‐Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin‐Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei‐Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Pulit, Sara L, Rannikmäe, Kristiina, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Rost, Natalia S, Rothwell, Peter M, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, Sale, Michele M, Salomaa, Veikko, Sapkota, Bishwa R, Schmidt, Reinhold, Schmidt, Carsten O, Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie LM, Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D, Thijs, Vincent NS, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Wassertheil‐Smoller, Sylvia, Wilson, James G, Yusuf, Salim, Amin, Najaf, Aparicio, Hugo S, Arnett, Donna K, Attia, John, Beiser, Alexa S, Berr, Claudine, Buring, Julie E, Bustamante, Mariana, Caso, Valeria, Cheng, Yu‐Ching, Hoan Choi, Seung, Chowhan, Ayesha, Cullell, Natalia, Dartigues, Jean‐François, Delavaran, Hossein, Delgado, Pilar, Dörr, Marcus, Engström, Gunnar, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Heitsch, Laura, Hozawa, Atsushi, Ibanez, Laura, Ilinca, Andreea, Ingelsson, Martin, Iwasaki, Motoki, Jackson, Rebecca D, Jood, Katarina, Jousilahti, Pekka, Kaffashian, Sara, Kalra, Lalit, Kamouchi, Masahiro, Kitazono, Takanari, Kjartansson, Olafur, Kloss, Manja, Koudstaal, Peter J, Krupinski, Jerzy, Labovitz, Daniel L, Laurie, Cathy C, Levi, Christopher R, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Lioutas, Vasileios, Mei Liu, Yong, Lopez, Oscar L, Makoto, Hirata, Martinez‐Majander, Nicolas, Matsuda, Koichi, Minegishi, Naoko, Montaner, Joan, Morris, Andrew P, Muiño, Elena, Müller‐Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Reddy Peddareddygari, Leema, Pedersen, Nancy L, Pera, Joanna, Perola, Markus, Pezzini, Alessandro, Pileggi, Silvana, Rabionet, Raquel, Riba‐Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Roquer, Jaume, Rudd, Anthony G, Sarin, Antti‐Pekka, Sarju, Ralhan, Sarnowski, Chloe, Sasaki, Makoto, Satizabal, Claudia L, Satoh, Mamoru, Sattar, Naveed, Sawada, Norie, Sibolt, Gerli, Sigurdsson, Ásgeir, Smith, Albert, Sobue, Kenji, Soriano‐Tárraga, Carolina, Stanne, Tara, Colin Stine, O, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Tanno, Kozo, Teumer, Alexander, Tomppo, Liisa, Torres‐Aguila, Nuria P, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Völzke, Henry, Wakai, Kenji, Weir, David, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Xu, Huichun, Yamaji, Taiki, Sanghera, Dharambir K, Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez‐Cadenas, Israel, Longstreth, W T, Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B, Kittner, Steven J, Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S, Howson, Joanna MM, Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Published
2022
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22. Bedside detection of intracranial midline shift using portable magnetic resonance imaging

Author

Sheth, Kevin N., Yuen, Matthew M., Mazurek, Mercy H., Cahn, Bradley A., Prabhat, Anjali M., Salehi, Sadegh, Shah, Jill T., By, Samantha, Welch, E. Brian, Sofka, Michal, Sacolick, Laura I., Kim, Jennifer A., Payabvash, Seyedmehdi, Falcone, Guido J., Gilmore, Emily J., Hwang, David Y., Matouk, Charles, Gordon-Kundu, Barbara, RN, Adrienne Ward, Petersen, Nils, Schindler, Joseph, Gobeske, Kevin T., Sansing, Lauren H., Sze, Gordon, Rosen, Matthew S., Kimberly, W. Taylor, and Kundu, Prantik

Published
2022
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25. White matter hyperintensity on MRI and plasma Aβ42/40 ratio additively increase the risk of cognitive impairment in hypertensive adults.

Author

de Havenon, Adam, Gottesman, Rebecca F., Willamson, Jeff D., Rost, Natalia, Sharma, Richa, Li, Vivian, Littig, Lauren, Stulberg, Eric, Falcone, Guido J., Prabhakaran, Shyam, Schneider, Andrea L. C., Sheth, Kevin N., Pajewski, Nicholas M., and Brickman, Adam M.

Abstract

INTRODUCTION: Dementia often involves comorbid Alzheimer's and vascular pathology, but their combined impact warrants additional study. METHODS: We analyzed the Systolic Blood Pressure Intervention Trial and categorized white matter hyperintensity (WMH) volume into highest versus lowest/mid tertile and the amyloid beta (Aβ)42/40 ratio into lowest versus mid/highest ratio tertile. Using these binary variables, we created four exposure categories: (1) combined low risk, (2) Aβ risk, (3) WMH risk, and (4) combined high risk. RESULTS: In the cohort of 467 participants (mean age 69.7 ± 7.1, 41.8% female, 31.9% nonwhite or Hispanic) during 4.8 years of follow‐up and across the four exposure categories the rates of cognitive impairment were 5.3%, 7.8%, 11.8%, and 22.6%. Compared to the combined low‐risk category, the adjusted hazard ratio for cognitive impairment was 4.12 (95% confidence interval, 1.71 to 9.94) in the combined high‐risk category. DISCUSSION: This study emphasizes the potential impact of therapeutic approaches to dementia prevention that target both vascular and amyloid pathology. Highlights: White matter hyperintensity (WMH) and plasma amyloid (Aβ42/40) are additive risk factors for the development of cognitive impairment in the SPRINT MIND trial.Individuals in the high‐risk categories of both WMH and Aβ42/40 had a near fivefold increase in risk of cognitive impairment during 4.8 years of follow‐up on average.These findings suggest that treatment strategies targeting both vascular health and amyloid burden warrant further research. [ABSTRACT FROM AUTHOR]

Published
2024
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26. APOE epsilon variants and composite risk of dementia, disability, and death in the health and retirement study.

Author

Clocchiatti‐Tuozzo, Santiago, Szejko, Natalia, Rivier, Cyprien A., Renedo, Daniela, Huo, Shufan, Sheth, Kevin N., Gill, Thomas M., and Falcone, Guido J.

Subjects
DEMENTIA risk factors, MORTALITY risk factors, RISK assessment, HEALTH status indicators, RESEARCH funding, SECONDARY analysis, RETIREMENT, DNA, DESCRIPTIVE statistics, APOLIPOPROTEINS, GENOTYPES, PROPORTIONAL hazards models
Abstract

Background: Clinical trials in older adults are increasingly focused on functional outcomes, and the composite outcome of dementia, disability, and death is gaining pivotal importance. Genetic variation, particularly the APOE epsilon(ε) variants, may modify responses to new treatments. Although APOE ε4 is known to influence these outcomes separately, the magnitude of its effect on this composite outcome remains unknown. We tested the hypothesis that APOE ε4 increases, whereas APOE ε2 decreases, the risk of a composite outcome of dementia, disability, and death. Methods: We evaluated clinical and genomic data from the Health and Retirement Study collected from 1992 to 2020. We used variants rs429358 and rs7412 to determine APOE genotypes, modeled dominantly (carriers/noncarriers). We conducted survival analysis, using multivariable Cox proportional hazards models with a composite endpoint of dementia, disability, and death. Our primary analysis evaluated participants with genetic data and no previous dementia or disability. In secondary analyses, we focused on persons aged > = 75 years without heart disease or stroke, a subpopulation increasingly important in clinical trials of older adults. Results: We included 14,527 participants in the primary analysis. Over a median of 18 (Interquartile Range [IQR] 12–24) years, 6711 (46%) participants developed the composite outcome. In Cox analyses, APOE ε4 associated with higher risk (HR:1.15, 95%CI:1.09–1.22) of the composite outcome, whereas APOE ε2 associated with lower risk (HR:0.92, 95%CI:0.86–0.99). In the secondary analysis, we included 3174 participants. Over a median of 7 (IQR 4–11) years, 1326 participants (42%) developed the composite outcome. In Cox analyses, APOE ε4 associated with higher risk (HR:1.25, 95%CI:1.10–1.41) of the composite outcome, whereas APOE ε2 associated with lower risk (HR:0.84, 95%CI:0.71–0.98). Conclusions: APOE ε variants are linked to the risk of dementia, disability, and death in older adults. By examining these variants in clinical trials, we can better elucidate how they might alter the effectiveness of tested interventions. Importantly, this genetic information could help identify participants who may have greater absolute benefit from such interventions. See related editorial by Nicholas M. Pajewski. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Rehabilitation Therapy Doses Are Low After Stroke and Predicted by Clinical Factors

Author

Young, Brittany M., Holman, E. Alison, Cramer, Steven C., Shah, Shreyansh, Griessenauer, Christoph J., Patel, Nirav, Lin, David J., Gee, Joey, Moon, Johnson, Schwertfeger, Julie, Jayaraman, Arun, Lee, Robert, Lansberg, Maarten, Payne, Jeremy, Patten, Carolynn, Cramer, Steven C., Holman, E. Alison, Agrawal, Kunal, Kissela, Brett, DeJong, Stacey, Cole, John, Silver, Brian, Cucchiara, Brett, Busza, Ania, Liew, Sook-Lei, Alderman, Susan, Hayes, Heather, Majersik, Jennifer J., Worrall, Brad, Tirschwell, David, Bushnell, Cheryl, El Husseini, Nada, Lee, Jin-Moo, and Falcone, Guido J.

Published
2023
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30. Analysis of shared heritability in common disorders of the brain

Author

Consortium, The Brainstorm, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K, Walters, Raymond K, Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J, Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A, Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H, Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-François, Duron, Emmanuelle, Vardarajan, Badri N, Reitz, Christiane, Goate, Alison M, Huentelman, Matthew J, Kamboh, M Ilyas, Larson, Eric B, Rogaeva, Ekaterina, St George-Hyslop, Peter, Hakonarson, Hakon, Kukull, Walter A, Farrer, Lindsay A, Barnes, Lisa L, Beach, Thomas G, Demirci, F Yesim, Head, Elizabeth, Hulette, Christine M, Jicha, Gregory A, Kauwe, John SK, Kaye, Jeffrey A, Leverenz, James B, Levey, Allan I, Lieberman, Andrew P, Pankratz, Vernon S, Poon, Wayne W, Quinn, Joseph F, Saykin, Andrew J, Schneider, Lon S, Smith, Amanda G, Sonnen, Joshua A, Stern, Robert A, Van Deerlin, Vivianna M, Van Eldik, Linda J, Harold, Denise, Russo, Giancarlo, Rubinsztein, David C, Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C, Hampel, Harald, Owen, Michael J, Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M, Schott, Jonathan M, Rossor, Martin, Lupton, Michelle K, Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C, Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, van der Lee, Sven J, De Jager, Philip L, Geschwind, Daniel H, Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I, Ransmayr, Gerhard, Hyman, Bradley T, Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, and Cuenca-Leon, Ester

Subjects
Biological Sciences, Genetics, Biological Psychology, Health Sciences, Psychology, Brain Disorders, Human Genome, Clinical Research, Neurosciences, Mental Illness, Mental Health, 2.1 Biological and endogenous factors, Neurological, Mental health, Brain Diseases, Genetic Variation, Genome-Wide Association Study, Humans, Mental Disorders, Phenotype, Quantitative Trait, Heritable, Risk Factors, Brainstorm Consortium, General Science & Technology
Abstract

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

Published
2018

31. Analysis of shared heritability in common disorders of the brain.

Author

Brainstorm Consortium, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K, Walters, Raymond K, Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J, Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A, Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H, Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-François, Duron, Emmanuelle, Vardarajan, Badri N, Reitz, Christiane, Goate, Alison M, Huentelman, Matthew J, Kamboh, M Ilyas, Larson, Eric B, Rogaeva, Ekaterina, St George-Hyslop, Peter, Hakonarson, Hakon, Kukull, Walter A, Farrer, Lindsay A, Barnes, Lisa L, Beach, Thomas G, Demirci, F Yesim, Head, Elizabeth, Hulette, Christine M, Jicha, Gregory A, Kauwe, John SK, Kaye, Jeffrey A, Leverenz, James B, Levey, Allan I, Lieberman, Andrew P, Pankratz, Vernon S, Poon, Wayne W, Quinn, Joseph F, Saykin, Andrew J, Schneider, Lon S, Smith, Amanda G, Sonnen, Joshua A, Stern, Robert A, Van Deerlin, Vivianna M, Van Eldik, Linda J, Harold, Denise, Russo, Giancarlo, Rubinsztein, David C, Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C, Hampel, Harald, Owen, Michael J, Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M, Rossor, Martin, Lupton, Michelle K, Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C, Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, van der Lee, Sven J, De Jager, Philip L, Geschwind, Daniel H, Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I, Ransmayr, Gerhard, Hyman, Bradley T, Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, and Furlotte, Nicholas

Subjects
Brainstorm Consortium, Humans, Brain Diseases, Risk Factors, Mental Disorders, Quantitative Trait, Heritable, Phenotype, Genetic Variation, Genome-Wide Association Study, Clinical Research, Neurosciences, Rare Diseases, Human Genome, Brain Disorders, Genetics, Mental Health, 2.1 Biological and endogenous factors, Mental health, Neurological, General Science & Technology
Abstract

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

Published
2018

32. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Author

Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten-Jacobs, Loes, Giese, Anne-Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chasman, Daniel I, Chen, Wei-Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Heckbert, Susan R, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I, Ikram, M Arfan, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez-Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin-Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei-Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Psaty, Bruce M, Pulit, Sara L, Rannikmäe, Kristiina, Reiner, Alexander P, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Ridker, Paul M, Rost, Natalia S, Rothwell, Peter M, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, and Sale, Michele M

Subjects
Biological Sciences, Genetics, Human Genome, Stroke, Clinical Research, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Computational Biology, Databases, Genetic, Epigenesis, Genetic, Female, Gene Regulatory Networks, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, INDEL Mutation, Linkage Disequilibrium, Male, Models, Genetic, Polymorphism, Single Nucleotide, Risk Factors, AFGen Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, International Genomics of Blood Pressure (iGEN-BP) Consortium, INVENT Consortium, STARNET, BioBank Japan Cooperative Hospital Group, COMPASS Consortium, EPIC-CVD Consortium, EPIC-InterAct Consortium, International Stroke Genetics Consortium, METASTROKE Consortium, Neurology Working Group of the CHARGE Consortium, NINDS Stroke Genetics Network, UK Young Lacunar DNA Study, MEGASTROKE Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

Published
2018

33. Burden of Ischemic and Hemorrhagic Stroke Across the US From 1990 to 2019

Author

Renedo, Daniela, primary, Acosta, Julian N., additional, Leasure, Audrey C., additional, Sharma, Richa, additional, Krumholz, Harlan M., additional, de Havenon, Adam, additional, Alahdab, Fares, additional, Aravkin, Aleksandr Y., additional, Aryan, Zahra, additional, Bärnighausen, Till Winfried, additional, Basu, Sanjay, additional, Burkart, Katrin, additional, Coberly, Kaleb, additional, Criqui, Michael H., additional, Dai, Xiaochen, additional, Desai, Rupak, additional, Dharmaratne, Samath Dhamminda, additional, Doshi, Rajkumar, additional, Elgendy, Islam Y., additional, Feigin, Valery L., additional, Filip, Irina, additional, Gad, Mohamed M., additional, Ghozy, Sherief, additional, Hafezi-Nejad, Nima, additional, Kalani, Rizwan, additional, Karaye, Ibraheem M., additional, Kisa, Adnan, additional, Krishnamoorthy, Vijay, additional, Lo, Warren, additional, Mestrovic, Tomislav, additional, Miller, Ted R., additional, Misganaw, Awoke, additional, Mokdad, Ali H., additional, Murray, Christopher J. L., additional, Natto, Zuhair S., additional, Radfar, Amir, additional, Ram, Pradhum, additional, Roth, Gregory A., additional, Seylani, Allen, additional, Shah, Nilay S., additional, Sharma, Purva, additional, Sheikh, Aziz, additional, Singh, Jasvinder A., additional, Song, Suhang, additional, Sotoudeh, Houman, additional, Vervoort, Dominique, additional, Wang, Cong, additional, Xiao, Hong, additional, Xu, Suowen, additional, Zand, Ramin, additional, Falcone, Guido J., additional, and Sheth, Kevin N., additional

Published
2024
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34. Radiomics-Based Prediction of Collateral Status from CT Angiography of Patients Following a Large Vessel Occlusion Stroke

Author

Avery, Emily W., primary, Abou-Karam, Anthony, additional, Abi-Fadel, Sandra, additional, Behland, Jonas, additional, Mak, Adrian, additional, Haider, Stefan P., additional, Zeevi, Tal, additional, Sanelli, Pina C., additional, Filippi, Christopher G., additional, Malhotra, Ajay, additional, Matouk, Charles C., additional, Falcone, Guido J., additional, Petersen, Nils, additional, Sansing, Lauren H., additional, Sheth, Kevin N., additional, and Payabvash, Seyedmehdi, additional

Published
2024
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35. APOE ε4 and Intracerebral Hemorrhage in Patients With Brain Arteriovenous Malformation

Author

Renedo, Daniela, primary, Rivier, Cyprien A., additional, Koo, Andrew B., additional, Sujijantarat, Nanthiya, additional, Clocchiatti-Tuozzo, Santiago, additional, Wu, Kane, additional, Torres-Lopez, Victor M., additional, Huo, Shufan, additional, Gunel, Murat, additional, de Havenon, Adam, additional, Sheth, Kevin N., additional, Matouk, Charles C., additional, and Falcone, Guido J., additional

Published
2024
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37. Abstract HUP3: Neighborhood Deprivation and Functional Outcomes Following Ischemic Stroke

Author

Kleinberg, Leah M, primary, Clocchiatti-Tuozzo, Santiago, additional, Rivier, Cyprien, additional, Torres Lopez, Victor M, additional, Kim, Jisoo, additional, Kitlen, Eva, additional, Kampp, Michael C, additional, Jasak, Sara, additional, Schindler, Joseph L, additional, Sansing, Lauren H, additional, Sheth, Kevin N, additional, and Falcone, Guido J, additional

Published
2024
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43. Abstract WMP53: Neighborhood Deprivation and Functional Outcomes Following Ischemic Stroke

Author

Kleinberg, Leah M, primary, Clocchiatti-Tuozzo, Santiago, additional, Rivier, Cyprien, additional, Torres Lopez, Victor M, additional, Kim, Jisoo, additional, Kitlen, Eva, additional, Kampp, Michael C, additional, Jasak, Sara, additional, Schindler, Joseph L, additional, Sansing, Lauren H, additional, Sheth, Kevin N, additional, and Falcone, Guido J, additional

Published
2024
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46. Abstract TP103: Association Between Neighborhood-Level Disadvantage and Patient-Reported Mental Health Outcomes in Intracerebral Hemorrhage Survivors

Author

Taylor, Christopher L, primary, Zabinska, Julia, additional, Falcone, Guido J, additional, Lalwani, Dheeraj, additional, Peasley, Emma, additional, Sansing, Lauren H, additional, Arora, Rohan, additional, Mena-Hurtado, Carlos, additional, Forman, Rachel, additional, de Havenon, Adam H, additional, Okpala, Munachi N, additional, Bushnell, Cheryl D, additional, Mullen, Michael T, additional, Cohen, Jordana, additional, Cohen, Debbie L, additional, Messe, Steven, additional, and Sheth, Kevin N, additional

Published
2024
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47. Abstract TMP84: Multi-Institutional Validation of an Automated Segmentation Tool for Intracerebral Hemorrhage (ICH) and Peri-Hematomal Edema (PHE) on Head CT

Author

TRAN, ANH TUAN, primary, Desser, Dmitriy, additional, Abou Karam, Gaby, additional, Zeevi, Tal, additional, Qureshi, Adnan I, additional, Werring, David J, additional, Malhotra, Ajay, additional, Falcone, Guido J, additional, Sheth, Kevin N, additional, Nawabi, Jawed, additional, and Payabvash, Seyedmehdi, additional

Published
2024
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49. Abstract WMP19: A Brain Care Score for Risk of Late-Life Depression: Data From the UK Biobank Cohort

Author

Singh, Sanjula D, primary, Rivier, Cyprien, additional, Oreskovic, Tin, additional, Carr, Sinclair, additional, Papier, Keren, additional, Chemali, Zeina, additional, Guiterrez-Martinez, Leidys, additional, Mallick, Akashleena, additional, Parodi, Livia, additional, Mayerhofer, Ernst, additional, Senff, Jasper, additional, Kourkoulis, Christina, additional, Marini, Sandro, additional, Clocchiatti-Tuozzo, Santiago, additional, Nunley, Courtney, additional, Newhouse, Amy, additional, Ouyang, An, additional, Westover, Michael B, additional, Tanzi, Rudolph, additional, Lazar, Ronald M, additional, Pikula, Aleksandra, additional, Ibrahim, Sarah, additional, Brouwers, H, additional, Howard, Virginia J, additional, Howard, George, additional, Yechoor, Nirupama, additional, van Duijn, Cornelia, additional, Littlejohns, Thomas, additional, Sheth, Kevin N, additional, Rosand, Jonathan, additional, Fricchione, Gregory, additional, Anderson, Christopher D, additional, and Falcone, Guido J, additional

Published
2024
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