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1. Impaired kidney function, cerebral small vessel disease and cognitive disorders: the Framingham Heart Study

Author

Kelly, Dearbhla M, Pinheiro, Adlin A, Koini, Marisa, Anderson, Christopher D, Aparicio, Hugo, Hofer, Edith, Kern, Daniela, Blacker, Deborah, DeCarli, Charles, Hwang, Shih-Jen, Viswanathan, Anand, Gonzales, Mitzi M, Beiser, Alexa S, Seshadri, Sudha, Schmidt, Reinhold, Demissie, Serkalem, and Romero, Jose R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Minority Health, Clinical Research, Acquired Cognitive Impairment, Kidney Disease, Neurosciences, Aging, Dementia, Cerebrovascular, Brain Disorders, Vascular Cognitive Impairment/Dementia, Hypertension, Alzheimer's Disease, Alzheimer's Disease Related Dementias (ADRD), Neurodegenerative, Neurological, Renal and urogenital, Humans, Female, Male, Cerebral Small Vessel Diseases, Aged, Renal Insufficiency, Chronic, Glomerular Filtration Rate, Cognitive Dysfunction, Middle Aged, Albuminuria, Risk Factors, Magnetic Resonance Imaging, Cohort Studies, Prognosis, Follow-Up Studies, Cognition Disorders, albuminuria, cerebral small vessel disease, CKD, cognitive impairment, dementia, hypertension, Urology & Nephrology, Clinical sciences
Abstract

Background and hypothesisIt remains unclear whether the relation of chronic kidney disease (CKD) with cognitive dysfunction is independent of blood pressure (BP). We evaluated kidney function in relation to premorbid BP measurements, cerebral small vessel disease (CSVD), and incident mild cognitive impairment (MCI) and dementia in Framingham Offspring Cohort participants.MethodsWe included Framingham Offspring participants free of dementia, attending an examination during midlife (exam cycle 6, baseline) for ascertainment of kidney function status, with brain magnetic resonance imaging late in life (exam cycles 7-9), cognitive outcome data, and available interim hypertension and BP assessments. We related CKD (estimated glomerular filtration rate

Published
2024

2. Association of MRI Visible Perivascular Spaces and Neurofilament Light Chain: The Framingham Heart Study

Author

Ekenze, Oluchi, Pinheiro, Adlin, Demissie, Serkalem, Aparicio, Hugo J, Charidimou, Andreas, Beiser, Alexa S, Satizabal, Claudia L, Kautz, Tiffany, DeCarli, Charles, Greenberg, Steven, Seshadri, Sudha, and Romero, Jose R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Acquired Cognitive Impairment, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Research, Biomedical Imaging, Neurosciences, Neurodegenerative, Dementia, Aging, Prevention, Vascular Cognitive Impairment/Dementia, Cerebrovascular, Neurological, Male, Humans, Female, Intermediate Filaments, Brain, Magnetic Resonance Imaging, Basal Ganglia, Longitudinal Studies, Cerebral Small Vessel Diseases, Alzheimer's disease, basal ganglia, cerebral small vessel disease, MRI visible perivascular spaces, neurofilament light chain, neuroaxonal injury, Alzheimer’s disease, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences, Biological psychology
Abstract

BackgroundNeurofilament light chain (NfL) is a marker of neuronal injury. Perivascular spaces (PVS) visible on magnetic resonance imaging (MRI) represent cerebral small vessel disease (CSVD) but their role as markers of neuronal injury needs further clarification.ObjectiveTo relate PVS burden according to brain topography and plasma NfL.MethodsFramingham Heart Study (FHS) participants with brain MRI and NfL measurements were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) using validated methods and categorized based on counts. A mixed region variable representing high burden PVS in either BG or CSO was assessed. Multivariable linear regression analyses were used to relate PVS burden to log-transformed NfL levels in models adjusted for age, sex, FHS cohort, time between MRI and clinic exam, and image view (model 1), vascular risk factors (model 2), and white matter hyperintensity volume, covert brain infarcts, and cerebral microbleeds (model 3).ResultsAmong 1,457 participants (68.1±8.5 years, 45% males), NfL levels increased with higher PVS burden. Multivariable analysis showed an association of high PVS burden strictly in BG with NfL (β= 0.117, 95% CI 0.014-0.221; p = 0.027), but attenuated in model 3. The associations were mainly in participants≥65 years (β= 0.122, 95% CI 0.015-0.229, p = 0.026), women (β= 0.156, 95% CI 0.024-0.288, p = 0.021), and APOE ɛ4 non-carriers (β= 0.140, 95% CI 0.017-0.263, p = 0.026).ConclusionsThe association of strictly BG high PVS burden with NfL suggests a role for PVS as markers of neuroaxonal injury, but our results are hypothesis generating and require further replication.

Published
2023

3. Aging, prevalence and risk factors of MRI-visible enlarged perivascular spaces

Author

Lara, Frances Rodriguez, Scruton, Ashlea Lynn, Pinheiro, Adlin, Demissie, Serkalem, Parva, Pedram, Charidimou, Andreas, Francis, Michael, Himali, Jayandra J, DeCarli, Charles, Beiser, Alexa, Seshadri, Sudha, and Romero, Jose R

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Clinical Sciences, Biological Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Cerebrovascular, Clinical Research, Vascular Cognitive Impairment/Dementia, Neurodegenerative, Brain Disorders, Cardiovascular, Prevention, Biomedical Imaging, Dementia, Alzheimer's Disease Related Dementias (ADRD), Aging, Acquired Cognitive Impairment, Aged, Biomarkers, Cerebral Small Vessel Diseases, Female, Humans, Magnetic Resonance Imaging, Male, Prevalence, Risk Factors, cerebral small vessel disease, neurological markers, aging, disease marker, perivascular spaces, Biochemistry and cell biology, Clinical sciences
Abstract

Background and purposeCerebral small vessel disease (CSVD) increases with age and is associated with stroke and cognitive decline. Enlarged Perivascular Spaces (ePVS) is an emerging marker of CSVD, but its prevalence over the life span remain unclear. We characterized the age and sex-specific prevalence of ePVS and relation to age-specific risk factors, in a large community-based sample.MethodsWe included 3,710 Framingham Heart Study participants with available brain MRI (average age 61.4±14.6, 46% men). ePVS burden was rated in the centrum semiovale (CSO) and basal ganglia (BG) regions. Individual vascular risk factors were related to ePVS burden in the CSO, BG, and mixed CSO-BG regions using multivariable adjusted ordinal logistic regression analysis.ResultsSevere ePVS prevalence increased with age in men and women, and paralleled increase in vascular risk factors, and prevention treatment use. Older age, hypertension (and resulting higher treatment use), higher systolic and diastolic blood pressure, and smoking were associated with higher burden of ePVS in the CSO, BG and mixed regions.ConclusionsOur observations reinforce the hypothesis that ePVS may be a marker of aging-driven brain vascular pathologies, and its association with vascular risk factors support their role as CSVD imaging biomarker.

Published
2022

4. Cortical superficial siderosis in the general population: The Framingham Heart and Rotterdam studies

Author

Shoamanesh, Ashkan, Akoudad, Saloua, Himali, Jayandra J, Beiser, Alexa S, DeCarli, Charles, Seshadri, Sudha, Ikram, M Arfan, Romero, Jose R, and Vernooij, Meike W

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Stroke, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Vascular Cognitive Impairment/Dementia, Neurosciences, Dementia, Cerebrovascular, Acquired Cognitive Impairment, Brain Disorders, Alzheimer's Disease Related Dementias (ADRD), Neurodegenerative, Aging, Neurological, Aged, Cerebral Amyloid Angiopathy, Cerebral Hemorrhage, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Siderosis, Brain microbleeds, cerebral amyloid angiopathy, cerebral hemorrhage, community, cortical superficial siderosis, stroke facilities, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract

ObjectiveWe aimed to characterize cortical superficial siderosis, its determinants and sequel, in community-dwelling older adults.MethodsThe sample consisted of Framingham (n = 1724; 2000-2009) and Rotterdam (n = 4325; 2005-2013) study participants who underwent brain MRI. In pooled individual-level analysis, we compared baseline characteristics in patients with cortical superficial siderosis to two reference groups: (i) persons without hemorrhagic MRI markers of cerebral amyloid angiopathy (no cortical superficial siderosis and no microbleeds) and (ii) those with presumed cerebral amyloid angiopathy based on the presence of strictly lobar microbleeds but without cortical superficial siderosis.ResultsAmong a total of 6049 participants, 4846 did not have any microbleeds or cortical superficial siderosis (80%), 401 had deep/mixed microbleeds (6.6%), 776 had strictly lobar microbleeds without cortical superficial siderosis (12.8%) and 26 had cortical superficial siderosis with/without microbleeds (0.43%). In comparison to participants without microbleeds or cortical superficial siderosis and to those with strictly lobar microbleeds but without cortical superficial siderosis, participants with cortical superficial siderosis were older (OR 1.09 per year, 95% CI 1.05, 1.14; p 999.99; p = 0.006). During a mean follow-up of 5.6 years, 42.4% participants with cortical superficial siderosis had a stroke (five intracerebral hemorrhage, two ischemic strokes and four undetermined strokes), 19.2% had transient neurological deficits and 3.8% developed incident dementia.ConclusionOur study adds supporting evidence to the association between cortical superficial siderosis and cerebral amyloid angiopathy within the general population. Community-dwelling persons with cortical superficial siderosis may be at high risk for intracerebral hemorrhage and future neurological events.

Published
2021

6. The progression of carotid atherosclerosis and imaging markers of dementia

Author

Baradaran, Hediyeh, Demissie, Serkalem, Himali, Jayandra J, Beiser, Alexa, Gupta, Ajay, Polak, Joseph F, DeCarli, Charles, Seshadri, Sudha, and Romero, Jose R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Atherosclerosis, Neurosciences, Aging, Cardiovascular, Clinical Research, atherosclerosis, carotid artery, carotid ultrasound, hippocampus, magnetic resonance imaging, Clinical sciences, Biological psychology
Abstract

IntroductionWe studied the association of carotid intima-media thickness (CIMT) with hippocampal volume (HV) in community dwelling individuals, testing the hypothesis that persons with carotid atherosclerosis progression would have lower HV.MethodsWe studied 1376 Framingham Offspring participants with two carotid ultrasounds and brain magnetic resonance imaging (MRIs). We used multivariable linear regression analyses to relate CIMT progression and HV and total brain volume. Regression models were adjusted for demographics and vascular risk factors, time interval between imaging examinations, and baseline CIMT. We assessed effect modification by hypertension treatment (HRx).ResultsParticipants with higher ICA IMT progression had significantly lower HV after adjustment for vascular risk factors and baseline IMT (standardized beta ± standard error: -0.067 ± 0.027, P = .01). We observed weaker association between ICA IMT change and HV among subjects treated for hypertension (β = -0.047, P = .19 vs β = -0.096, P = .026).DiscussionCumulative vascular risk factor exposure, reflected by CIMT progression, may increase the risk of neurodegeneration.

Published
2020

7. Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna) : Update from the Advisory Committee on Immunization Practices — United States, July 2021

Author

Rosenblum, Hannah G., Hadler, Stephen C., Moulia, Danielle, Shimabukuro, Tom T., Su, John R., Tepper, Naomi K., Ess, Kevin C., Woo, Emily Jane, Mba-Jonas, Adamma, Alimchandani, Meghna, Nair, Narayan, Klein, Nicola P., Hanson, Kayla E., Markowitz, Lauri E., Wharton, Melinda, McNally, Veronica V., Romero, José R., Talbot, H. Keipp, Lee, Grace M., Daley, Matthew F., Mbaeyi, Sarah A., and Oliver, Sara E.

Published
2021

8. Use of mRNA COVID-19 Vaccine After Reports of Myocarditis Among Vaccine Recipients : Update from the Advisory Committee on Immunization Practices — United States, June 2021

Author

Gargano, Julia W., Wallace, Megan, Hadler, Stephen C., Langley, Gayle, Su, John R., Oster, Matthew E., Broder, Karen R., Gee, Julianne, Weintraub, Eric, Shimabukuro, Tom, Scobie, Heather M., Moulia, Danielle, Markowitz, Lauri E., Wharton, Melinda, McNally, Veronica V., Romero, José R., Talbot, H. Keipp, Lee, Grace M., Daley, Matthew F., and Oliver, Sara E.

Published
2021

9. 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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10. The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine in Adolescents Aged 12–15 Years — United States, May 2021

Author

Wallace, Megan, Woodworth, Kate R., Gargano, Julia W., Scobie, Heather M., Blain, Amy E., Moulia, Danielle, Chamberland, Mary, Reisman, Nicole, Hadler, Stephen C., MacNeil, Jessica R., Campos-Outcalt, Doug, Morgan, Rebecca L., Daley, Matthew F., Romero, José R., Talbot, H. Keipp, Lee, Grace M., Bell, Beth P., and Oliver, Sara E.

Published
2021

11. Updated Recommendations from the Advisory Committee on Immunization Practices for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of Thrombosis with Thrombocytopenia Syndrome Among Vaccine Recipients — United States, April 2021

Author

MacNeil, Jessica R., Su, John R., Broder, Karen R., Guh, Alice Y., Gargano, Julia W., Wallace, Megan, Hadler, Stephen C., Scobie, Heather M., Blain, Amy E., Moulia, Danielle, Daley, Matthew F., McNally, Veronica V., Romero, José R., Talbot, H. Keipp, Lee, Grace M., Bell, Beth P., and Oliver, Sara E.

Published
2021

13. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Author

Chauhan, Ganesh, Adams, Hieab HH, Satizabal, Claudia L, Bis, Joshua C, Teumer, Alexander, Sargurupremraj, Muralidharan, Hofer, Edith, Trompet, Stella, Hilal, Saima, Smith, Albert Vernon, Jian, Xueqiu, Malik, Rainer, Traylor, Matthew, Pulit, Sara L, Amouyel, Philippe, Mazoyer, Bernard, Zhu, Yi-Cheng, Kaffashian, Sara, Schilling, Sabrina, Beecham, Gary W, Montine, Thomas J, Schellenberg, Gerard D, Kjartansson, Olafur, Guðnason, Vilmundur, Knopman, David S, Griswold, Michael E, Windham, B Gwen, Gottesman, Rebecca F, Mosley, Thomas H, Schmidt, Reinhold, Saba, Yasaman, Schmidt, Helena, Takeuchi, Fumihiko, Yamaguchi, Shuhei, Nabika, Toru, Kato, Norihiro, Rajan, Kumar B, Aggarwal, Neelum T, De Jager, Philip L, Evans, Denis A, Psaty, Bruce M, Rotter, Jerome I, Rice, Kenneth, Lopez, Oscar L, Liao, Jiemin, Chen, Christopher, Cheng, Ching-Yu, Wong, Tien Y, Ikram, Mohammad K, van der Lee, Sven J, Amin, Najaf, Chouraki, Vincent, DeStefano, Anita L, Aparicio, Hugo J, Romero, Jose R, Maillard, Pauline, DeCarli, Charles, Wardlaw, Joanna M, del C. Valdés Hernández, Maria, Luciano, Michelle, Liewald, David, Deary, Ian J, Starr, John M, Bastin, Mark E, Maniega, Susana Muñoz, Slagboom, P Eline, Beekman, Marian, Deelen, Joris, Uh, Hae-Won, Lemmens, Robin, Brodaty, Henry, Wright, Margaret J, Ames, David, Boncoraglio, Giorgio B, Hopewell, Jemma C, Beecham, Ashley H, Blanton, Susan H, Wright, Clinton B, Sacco, Ralph L, Wen, Wei, Thalamuthu, Anbupalam, Armstrong, Nicola J, Chong, Elizabeth, Schofield, Peter R, Kwok, John B, van der Grond, Jeroen, Stott, David J, Ford, Ian, Jukema, J Wouter, Vernooij, Meike W, Hofman, Albert, Uitterlinden, André G, van der Lugt, Aad, Wittfeld, Katharina, Grabe, Hans J, Hosten, Norbert, von Sarnowski, Bettina, Völker, Uwe, Levi, Christopher, and Jimenez-Conde, Jordi

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Genetics, Stroke, Cardiovascular, Aging, Human Genome, Prevention, Cerebrovascular, Brain Disorders, 2.1 Biological and endogenous factors, Good Health and Well Being, Stroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), METASTROKE, Alzheimer's Disease Genetics Consortium (ADGC), and the Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.MethodsWe performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.ResultsThe mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy.ConclusionIn this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.

Published
2019

23. Analysis of Repair Costs of Scholar Buildings Affected by Earthquakes Using Data Mining. Case Study: Earthquakes of 2017 in Mexico

Author

García-Rueda, Graciela, Valdovinos, Rosa M., Valdés-González, Jesús, Alejo, Roberto, González-Ruiz, J. Leonardo, Marcial-Romero, José R., Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Figueroa Mora, Karina Mariela, editor, Anzurez Marín, Juan, editor, Cerda, Jaime, editor, Carrasco-Ochoa, Jesús Ariel, editor, Martínez-Trinidad, José Francisco, editor, and Olvera-López, José Arturo, editor

Published
2020
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28. Blood Viral Load in Symptomatic Congenital Cytomegalovirus Infection

Author

Collaborative Antiviral Study Group (CASG), Marsico, Concetta, Aban, Immaculada, Kuo, Huichien, James, Scott H., Sanchez, Pablo J., Ahmed, Amina, Arav-Boger, Ravit, Michaels, Marian G., Ashouri, Negar, Englund, Janet A., Estrada, Benjamin, Jacobs, Richard F., Romero, José R., Sood, Sunil K., Whitworth, Suzanne, Jester, Penelope M., Whitley, Richard J., and Kimberlin, David W.

Published
2019

30. Inflammatory biomarkers, cerebral microbleeds, and small vessel disease

Author

Shoamanesh, Ashkan, Preis, Sarah R, Beiser, Alexa S, Vasan, Ramachandran S, Benjamin, Emelia J, Kase, Carlos S, Wolf, Philip A, DeCarli, Charles, Romero, Jose R, and Seshadri, Sudha

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Acquired Cognitive Impairment, Dementia, Neurodegenerative, Neurosciences, Clinical Research, Stroke, Brain Disorders, Vascular Cognitive Impairment/Dementia, Aging, Alzheimer's Disease Related Dementias (ADRD), Cerebrovascular, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, Aged, Biomarkers, Cerebral Hemorrhage, Cerebral Small Vessel Diseases, Cross-Sectional Studies, Female, Humans, Inflammation Mediators, Male, Massachusetts, Middle Aged, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveWe investigated the association between circulating biomarkers of inflammation and MRI markers of small vessel disease.MethodsWe performed a cross-sectional study relating a panel of 15 biomarkers, representing systemic inflammation (high-sensitivity C-reactive protein, interleukin-6, monocyte chemotactic protein-1, tumor necrosis factor α, tumor necrosis factor receptor 2, osteoprotegerin, and fibrinogen), vascular inflammation (intercellular adhesion molecule 1, CD40 ligand, P-selectin, lipoprotein-associated phospholipase A2 mass and activity, total homocysteine, and vascular endothelial growth factor), and oxidative stress (myeloperoxidase) to ischemic (white matter hyperintensities/silent cerebral infarcts) and hemorrhagic (cerebral microbleeds) markers of cerebral small vessel disease (CSVD) on MRI in 1,763 stroke-free Framingham offspring (mean age 60.2 ± 9.1 years, 53.7% women).ResultsWe observed higher levels of circulating tumor necrosis factor receptor 2 and myeloperoxidase in the presence of cerebral microbleed (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1-4.1 and OR 1.5, 95% CI 1.1-2.0, respectively), higher levels of osteoprotegerin (OR 1.1, 95% CI 1.0-1.2), intercellular adhesion molecule 1 (OR 1.7, 95% CI 1.1-2.5), and lipoprotein-associated phospholipase A2 mass (OR 1.5, 95% CI 1.1-2.1), and lower myeloperoxidase (OR 0.8, 95% CI 0.7-1.0) in participants with greater white matter hyperintensity volumes and silent cerebral infarcts.ConclusionsOur study supports a possible role for inflammation in the pathogenesis of CSVD, but suggests that differing inflammatory pathways may underlie ischemic and hemorrhagic subtypes. If validated in other samples, these biomarkers may improve stroke risk prognostication and point to novel therapeutic targets to combat CSVD.

Published
2015

31. Abstract TP39: Multi-Marker Cerebral Small Vessel Disease Score and Risk of Incident Depression: The Framingham Heart Study

Author

Araujo Contreras, Robert, primary, Pinheiro, Adlin, additional, Ekenze, Oluchi, additional, Aparicio, Hugo J, additional, Beiser, Alexa, additional, Himali, Jayandra J, additional, Lioutas, Vasileios, additional, De Carli, Charles, additional, Seshadri, Sudha, additional, Demissie, Serkalem, additional, and Romero, Jose R, additional

Published
2024
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33. Abstract WP239: Apolipoprotein E4 Allele Effect on the Prevalence of Intracranial Large Artery Stenosis

Author

Lopez-Navarro, Edgar R, primary, Khasiyev, Farid, additional, Spagnolo-Allende, Antonio J, additional, Guzman, Vanessa A, additional, Strobino, Kevin, additional, Liu, Minghua, additional, Del Brutto, Oscar, additional, Sanchez, Danurys, additional, Hilal, Saima, additional, Elkind, Mitchell, additional, Rundek, Tatjana, additional, Del, Victor J, additional, Brickman, Adam, additional, Manly, Jennifer, additional, Andrews, Howard, additional, Seshadri, Sudha, additional, Romero, Jose R, additional, Chen, Christopher, additional, and Gutierrez, Jose, additional

Published
2024
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34. Abstract TP15: Association Between Prevalent Cardiovascular Disease Plus Atrial Fibrillation and Global Cerebral Small Vessel Disease- The Framingham Heart Study

Author

Ekenze, Oluchi, primary, Pinheiro, Adlin, additional, Beiser, Alexa, additional, Lioutas, Vasileios, additional, Benjamin, Emelia J, additional, Vasan, Ramachandran, additional, De Carli, Charles, additional, Seshadri, Sudha, additional, Demissie, Serkalem, additional, and Romero, Jose R, additional

Published
2024
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38. Association of brain arterial diameters with demographic and anatomical factors in a multi-national pooled analysis of cohort studies.

Author

Del Brutto, Victor J, Khasiyev, Farid, Liu, Minghua, Spagnolo-Allende, Antonio, Qiao, Ye, Melgarejo Arias, Jesus D, Guzman, Vanessa A, Igwe, Kay C, Sanchez, Danurys L, Andrews, Howard, Morales, Clarissa D, Farrell, Meagan T, Bassil, Darina T, Seshadri, Sudha, Wagner, Ryan G, Mngomezulu, Victor, Manly, Jennifer, Elkind, Mitchell SV, Berkman, Lisa, and Romero, Jose R

Abstract

Background and Purpose: Brain arterial diameters are markers of cerebrovascular disease. Demographic and anatomical factors may influence arterial diameters. We hypothesize that age, sex, height, total cranial volume (TCV), and persistent fetal posterior cerebral artery (fPCA) correlate with brain arterial diameters across populations. Methods: Participants had a time-of-flight MRA from nine international cohorts. Arterial diameters of the cavernous internal carotid arteries (ICA), middle cerebral arteries (MCA), and basilar artery (BA) were measured using LAVA software. Regression models assessed the association between exposures and brain arterial diameters. Results: We included 6,518 participants (mean age: 70 ± 9 years; 41% men). Unilateral fPCA was present in 13.2% and bilateral in 3.2%. Larger ICA, MCA, and BA diameters correlated with older age (Weighted average [WA] per 10 years: 0.18 mm, 0.11 mm, and 0.12 mm), male sex (WA: 0.24 mm, 0.13 mm, and 0.21 mm), and TCV (WA: for one TCV standard deviation: 0.24 mm, 0.29 mm, and 0.18 mm). Unilateral and bilateral fPCAs showed a positive correlation with ICA diameters (WA: 0.39 mm and 0.73 mm) and negative correlation with BA diameters (WA: −0.88 mm and −1.73 mm). Regression models including age, sex, TCV, and fPCA explained on average 15%, 13%, and 25% of the ICA, MCA, and BA diameter interindividual variation, respectively. Using height instead of TCV as a surrogate of head size decreased the R-squared by 3% on average. Conclusion: Brain arterial diameters correlated with age, sex, TCV, and fPCA. These factors should be considered when defining abnormal diameter cutoffs across populations. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Association of brain arterial diameters with demographic and anatomical factors in a multi-national pooled analysis of cohort studies

Author

Del Brutto, Victor J, primary, Khasiyev, Farid, additional, Liu, Minghua, additional, Spagnolo-Allende, Antonio, additional, Qiao, Ye, additional, Melgarejo Arias, Jesus D, additional, Guzman, Vanessa A, additional, Igwe, Kay C, additional, Sanchez, Danurys L., additional, Andrews, Howard, additional, Morales, Clarissa D, additional, Farrell, Meagan T, additional, Bassil, Darina T, additional, Seshadri, Sudha, additional, Wagner, Ryan G, additional, Mngomezulu, Victor, additional, Manly, Jennifer, additional, Elkind, Mitchell SV, additional, Berkman, Lisa, additional, Romero, Jose R, additional, Maestre, Gladys E, additional, Del Brutto, Oscar H, additional, Brickman, Adam M, additional, Venketasubramanian, Narayanaswamy, additional, Chen, Christopher, additional, Robert, Caroline, additional, Hilal, Saima, additional, Rundek, Tatjana, additional, Wasserman, Bruce A, additional, and Gutierrez, Jose, additional

Published
2023
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