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1. Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆

Author: Frid, P., Xu, H., Mitchell, B.D., Drake, M., Wasselius, J., Gaynor, B., Ryan, K., Giese, A.K., Schirmer, M., Donahue, K.L., Irie, R., Bouts, M.J.R.J., McIntosh, E.C., Mocking, S.J.T., Dalca, A.V., Giralt-Steinhauer, E., Holmegaard, L., Jood, K., Roquer, J., Cole, J.W., McArdle, P.F., Broderick, J.P., Jimenez-Conde, J., Jern, C., Kissela, B.M., Kleindorfer, D.O., Lemmens, R., Meschia, J.F., Rosand, J., Rundek, T., Sacco, R.L., Schmidt, R., Sharma, P., Slowik, A., Thijs, V., Woo, D., Worrall, B.B., Kittner, S.J., Petersson, J., Golland, P., Wu, O., Rost, N.S., and Lindgren, A.
Published: 2022
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2. Primary stroke prevention worldwide: translating evidence into action.

Author: Owolabi M.O., Thrift A.G., Mahal A., Ishida M., Martins S., Johnson W.D., Pandian J., Abd-Allah F., Yaria J., Phan H.T., Roth G., Gall S.L., Beare R., Phan T.G., Mikulik R., Akinyemi R.O., Norrving B., Brainin M., Feigin V.L., Abanto C., Abera S.F., Addissie A., Adebayo O., Adeleye A.O., Adilbekov Y., Adilbekova B., Adoukonou T.A., Aguiar de Sousa D., Ajagbe T., Akhmetzhanova Z., Akpalu A., Alvarez Ahlgren J., Ameriso S., Andonova S., Awoniyi F.E., Bakhiet M., Barboza M., Basri H., Bath P., Bello O., Bereczki D., Beretta S., Berkowitz A., Bernabe-Ortiz A., Bernhardt J., Berzina G., Bisharyan M., Bovet P., Budincevic H., Cadilhac D., Caso V., Chen C., Chin J., Chwojnicki K., Conforto A., Cruz V.T., D'Amelio M., Danielyan K., Davis S., Demarin V., Dempsey R., Dichgans M., Dokova K., Donnan G., Elkind M.S., Endres M., Fischer U., Gankpe F., Gaye Saavedra A., Gil A., Giroud M., Gnedovskaya E., Hachinski V., Hafdi M., Hamadeh R., Hamzat T.K., Hankey G., Heldner M., Ibrahim E.A., Ibrahim N.M., Inoue M., Jee S., Jeng J.-S., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Khan T., Kiechl S., Kondybayeva A., Korv J., Kravchenko M., Krishnamurthi R.V., Kruja J., Lakkhanaloet M., Langhorne P., Lavados P.M., Law Z.K., Lawal A., Lazo-Porras M., Lebedynets D., Lee T.-H., Leung T., Liebeskind D.S., Lindsay P., Lopez-Jaramillo P., Lotufo P.A., Machline-Carrion J., Makanjuola A., Markus H.S., Marquez-Romero J.M., Medina M., Medukhanova S., Mehndiratta M.M., Merkin A., Mirrakhimov E., Mohl S., Moscoso-Porras M., Muller-Stierlin A., Murphy S., Musa K.I., Nasreldein A., Nogueira R.G., Nolte C., Noubiap J.J., Novarro-Escudero N., Ogun Y., Oguntoye R.A., Oraby M.I., Osundina M., Ovbiagele B., Orken D.N., Ozdemir A.O., Ozturk S., Paccot M., Phromjai J., Piradov P., Platz T., Potpara T., Ranta A., Rathore F., Richard E., Sacco R.L., Sahathevan R., Santos Carquin I., Saposnik G., Sarfo F.S., Sharma M., Sheth K., Shobhana A., Suwanwela N., Svyato I., Sylaja P.N., Tao X., Thakur K.T., Toni D., Topcuoglu M.A., Torales J., Towfighi A., Truelsen T.C., Tsiskaridze A., Tulloch-Reid M., Useche N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K.W., Wang W., Wijeratne T., Wolfe C., Yifru Y.M., Yock-Corrales A., Yonemoto N., Yperzeele L., Zhang P., Owolabi M.O., Thrift A.G., Mahal A., Ishida M., Martins S., Johnson W.D., Pandian J., Abd-Allah F., Yaria J., Phan H.T., Roth G., Gall S.L., Beare R., Phan T.G., Mikulik R., Akinyemi R.O., Norrving B., Brainin M., Feigin V.L., Abanto C., Abera S.F., Addissie A., Adebayo O., Adeleye A.O., Adilbekov Y., Adilbekova B., Adoukonou T.A., Aguiar de Sousa D., Ajagbe T., Akhmetzhanova Z., Akpalu A., Alvarez Ahlgren J., Ameriso S., Andonova S., Awoniyi F.E., Bakhiet M., Barboza M., Basri H., Bath P., Bello O., Bereczki D., Beretta S., Berkowitz A., Bernabe-Ortiz A., Bernhardt J., Berzina G., Bisharyan M., Bovet P., Budincevic H., Cadilhac D., Caso V., Chen C., Chin J., Chwojnicki K., Conforto A., Cruz V.T., D'Amelio M., Danielyan K., Davis S., Demarin V., Dempsey R., Dichgans M., Dokova K., Donnan G., Elkind M.S., Endres M., Fischer U., Gankpe F., Gaye Saavedra A., Gil A., Giroud M., Gnedovskaya E., Hachinski V., Hafdi M., Hamadeh R., Hamzat T.K., Hankey G., Heldner M., Ibrahim E.A., Ibrahim N.M., Inoue M., Jee S., Jeng J.-S., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Khan T., Kiechl S., Kondybayeva A., Korv J., Kravchenko M., Krishnamurthi R.V., Kruja J., Lakkhanaloet M., Langhorne P., Lavados P.M., Law Z.K., Lawal A., Lazo-Porras M., Lebedynets D., Lee T.-H., Leung T., Liebeskind D.S., Lindsay P., Lopez-Jaramillo P., Lotufo P.A., Machline-Carrion J., Makanjuola A., Markus H.S., Marquez-Romero J.M., Medina M., Medukhanova S., Mehndiratta M.M., Merkin A., Mirrakhimov E., Mohl S., Moscoso-Porras M., Muller-Stierlin A., Murphy S., Musa K.I., Nasreldein A., Nogueira R.G., Nolte C., Noubiap J.J., Novarro-Escudero N., Ogun Y., Oguntoye R.A., Oraby M.I., Osundina M., Ovbiagele B., Orken D.N., Ozdemir A.O., Ozturk S., Paccot M., Phromjai J., Piradov P., Platz T., Potpara T., Ranta A., Rathore F., Richard E., Sacco R.L., Sahathevan R., Santos Carquin I., Saposnik G., Sarfo F.S., Sharma M., Sheth K., Shobhana A., Suwanwela N., Svyato I., Sylaja P.N., Tao X., Thakur K.T., Toni D., Topcuoglu M.A., Torales J., Towfighi A., Truelsen T.C., Tsiskaridze A., Tulloch-Reid M., Useche N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K.W., Wang W., Wijeratne T., Wolfe C., Yifru Y.M., Yock-Corrales A., Yonemoto N., Yperzeele L., and Zhang P.
Abstract: Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Published: 2022

3. The state of stroke services across the globe: Report of World Stroke Organization-World Health Organization surveys.

Author: Owolabi M.O., Thrift A.G., Martins S., Johnson W., Pandian J., Abd-Allah F., Varghese C., Mahal A., Yaria J., Phan H.T., Gall S.L., Beare R., Phan T.G., Mikulik R., Feigin V.L., on behalf of the Stroke Experts Collaboration Group, Abera S.F., Addissie A., Adeleye A., Adilbekov Y., Adilbekova B., Adoukonou T.A., Aguiar D.S.D., Akhmetzhanova Z., Akinyemi R.O., Akpalu A., Ameriso S.F., Andonova S., Abanto C., Awoniyi F.E., Bakhiet M., Basri H., Bath P.M., Bereczki D., Beretta S., Berkowitz A.L., Bernhardt J., Berzina G., Bhavsar B., Bisharyan M.S., Bovet P., Brainin M., Budincevic H., Cabral N.L., Cadilhac D.A., Caso V., Chen C., Chin J.H., Christensen H., Chwojnicki K., Conforto A.B., Cruz V.T., D'Amelio M., Danielyan K.E., Davis S., Demarin V., Dempsey R.J., Dichgans M., Dokova, Donnan G., Duran J., Elizondo M.A.B., Elkind M.S., Endres M., Etedal I., Faris M.E., Fischer U., Gankpe F., Gavidia M., Gaye-Saavedra A., Giroud M., Gongora-Rivera F., Hachinski V., Hacke W., Hamadeh R.R., Hamzat T.K., Hankey G.J., Heldner M.R., Ibrahim N.M., Inoue M., Jee S., Jiann-Shing J., Johnston S., Kalkonde Y., Kamenova S., Kelly P., Khan T., Kiechl S., Kondybayeva A., Korv J., Kravchenko M., Krishnamurthi R., Langhorne P., Kang Z.L., Kruja J., Lavados P.M., Lebedynets D., Leung T.W., Liebeskind D.S., Lindsay P., Liu L., Lopez-Jaramillo P., Lotufo P.A., Machline-Carrion J.M., Markus H.S., Marquez-Romero J.M., Medina M.T., Medukhanova S., Mehndiratta M.M., Mirrakhimov E., Mohl S., Murphy S., Musa K.I., Nasreldein A., Nogueira R., Nolte C.H., Norrving B., Noubiap J.J., Novarro-Escudero N., O'Donnell M., Ogun V., Oraby M.I., Ovbiagele B., Orken D.N., Ozdemir A.O., Ozturk S., Paccot M., Peters A., Piradov M., Platz T., Potpara T., Ranta A., Rathore F.A., Roth G., Sacco R.L., Sahathevan R., Santos I.C., Saposnik G., Sarfo F.S., Sharma M., Sheth K.N., Shobhana A., Silva S.N., Suwanwela N., Sylaja P.N., Thakur K., Toni D., Topcuoglu M.A., Torales J., Towfighi A., Truelsen T., Tsiskaridze A., Tsong-Hai L., Tulloch-Reid M., Useche J.N., Vanacker P., Vassilopoulou S., Venketasubramanian N., Vukorepa G., Vuletic V., Wahab K.W., Wang W., Wijeratne T., Wolfe C., Yifru M.Y., Yock-Corrales A., Yonemoto N., Yperzeele L., Owolabi M.O., Thrift A.G., Martins S., Johnson W., Pandian J., Abd-Allah F., Varghese C., Mahal A., Yaria J., Phan H.T., Gall S.L., Beare R., Phan T.G., Mikulik R., Feigin V.L., on behalf of the Stroke Experts Collaboration Group, Abera S.F., Addissie A., Adeleye A., Adilbekov Y., Adilbekova B., Adoukonou T.A., Aguiar D.S.D., Akhmetzhanova Z., Akinyemi R.O., Akpalu A., Ameriso S.F., Andonova S., Abanto C., Awoniyi F.E., Bakhiet M., Basri H., Bath P.M., Bereczki D., Beretta S., Berkowitz A.L., Bernhardt J., Berzina G., Bhavsar B., Bisharyan M.S., Bovet P., Brainin M., Budincevic H., Cabral N.L., Cadilhac D.A., Caso V., Chen C., Chin J.H., Christensen H., Chwojnicki K., Conforto A.B., Cruz V.T., D'Amelio M., Danielyan K.E., Davis S., Demarin V., Dempsey R.J., Dichgans M., Dokova, Donnan G., Duran J., Elizondo M.A.B., Elkind M.S., Endres M., Etedal I., Faris M.E., Fischer U., Gankpe F., Gavidia M., Gaye-Saavedra A., Giroud M., Gongora-Rivera F., Hachinski V., Hacke W., Hamadeh R.R., Hamzat T.K., Hankey G.J., Heldner M.R., Ibrahim N.M., Inoue M., Jee S., Jiann-Shing J., Johnston S., Kalkonde Y., Kamenova S., Kelly P., Khan T., Kiechl S., Kondybayeva A., Korv J., Kravchenko M., Krishnamurthi R., Langhorne P., Kang Z.L., Kruja J., Lavados P.M., Lebedynets D., Leung T.W., Liebeskind D.S., Lindsay P., Liu L., Lopez-Jaramillo P., Lotufo P.A., Machline-Carrion J.M., Markus H.S., Marquez-Romero J.M., Medina M.T., Medukhanova S., Mehndiratta M.M., Mirrakhimov E., Mohl S., Murphy S., Musa K.I., Nasreldein A., Nogueira R., Nolte C.H., Norrving B., Noubiap J.J., Novarro-Escudero N., O'Donnell M., Ogun V., Oraby M.I., Ovbiagele B., Orken D.N., Ozdemir A.O., Ozturk S., Paccot M., Peters A., Piradov M., Platz T., Potpara T., Ranta A., Rathore F.A., Roth G., Sacco R.L., Sahathevan R., Santos I.C., Saposnik G., Sarfo F.S., Sharma M., Sheth K.N., Shobhana A., Silva S.N., Suwanwela N., Sylaja P.N., Thakur K., Toni D., Topcuoglu M.A., Torales J., Towfighi A., Truelsen T., Tsiskaridze A., Tsong-Hai L., Tulloch-Reid M., Useche J.N., Vanacker P., Vassilopoulou S., Venketasubramanian N., Vukorepa G., Vuletic V., Wahab K.W., Wang W., Wijeratne T., Wolfe C., Yifru M.Y., Yock-Corrales A., Yonemoto N., and Yperzeele L.
Abstract: Background: Improving stroke services is critical for reducing the global stroke burden. The World Stroke Organization-World Health Organization-Lancet Neurology Commission on Stroke conducted a survey of the status of stroke services in low and middle-income countries (LMICs) compared to high-income countries. Method(s): Using a validated World Stroke Organization comprehensive questionnaire, we collected and compared data on stroke services along four pillars of the stroke quadrangle (surveillance, prevention, acute stroke, and rehabilitation) in 84 countries across World Health Organization regions and economic strata. The World Health Organization also conducted a survey of non-communicable diseases in 194 countries in 2019. Result(s): Fewer surveillance activities (including presence of registries, presence of recent risk factors surveys, and participation in research) were reported in low-income countries than high-income countries. The overall global score for prevention was 40.2%. Stroke units were present in 91% of high-income countries in contrast to 18% of low-income countries (p < 0.001). Acute stroke treatments were offered in ~ 60% of high-income countries compared to 26% of low-income countries (p = 0.009). Compared to high-income countries, LMICs provided less rehabilitation services including in-patient rehabilitation, home assessment, community rehabilitation, education, early hospital discharge program, and presence of rehabilitation protocol. Conclusion(s): There is an urgent need to improve access to stroke units and services globally especially in LMICs. Countries with less stroke services can adapt strategies from those with better services. This could include establishment of a framework for regular monitoring of stroke burden and services, implementation of integrated prevention activities and essential acute stroke care services, and provision of interdisciplinary care for stroke rehabilitation.Copyright © 2021 World Stroke Organization.
Published: 2021

4. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke

Author: Mohr, J.P., Thompson, J.L.P., Lazar, R.M., Levin, B., Sacco, R.L., Furie, K.L., Kistler, J.P., Albers, G.W., Pettigrew, L.C., Adams, H.P., Jr., Jackson, C.M., and Pullicino, P.
Subjects: Stroke (Disease) -- Prevention, Aspirin -- Evaluation, Warfarin -- Evaluation
Abstract: Warfarin and aspirin appear to be equally effective in preventing a second stroke in stroke patients, according to a study of 2,206 patients. The rate of major hemorrhage or bleeding was also similar for either treatment.
Published: 2001

5. Primary end-point times, functional outcome and adverse event profile after acute ischaemic stroke

Author: Ali, M., Sacco, R.L., and Lees, K.R.
Published: 2009
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6. Common genetic variation indicates separate causes for periventricular and deep white matter hyperintensities

Author: Armstrong, N.J., Mather, K.A., Sargurupremraj, M., Knol, M.J., Malik, R., Satizabal, C.L., Yanek, L.R., Wen, W., Gudnason, V.G., Dueker, N.D., Elliott, L.T., Hofer, E., Bis, J., Jahanshad, N., Li, S., Logue, M.A., Luciano, M., Scholz, M., Smith, A.V., Trompet, S., Vojinovic, D., Xia, R., Alfaro-Almagro, F., Ames, D., Amin, N., Amouyel, P., Beiser, A.S., Brodaty, H., Deary, I.J., Fennema-Notestine, C., Gampawar, P.G., Gottesman, R., Griffanti, L., Jack, C.R., Jenkinson, M., Jiang, J., Kral, B.G., Kwok, J.B., Lampe, L., Liewald, D.C.M., Maillard, P., Marchini, J., Bastin, M.E., Mazoyer, B., Pirpamer, L., Romero, J.R., Roshchupkin, G.V., Schofield, P.R., Schroeter, M.L., Stott, D.J., Thalamuthu, A., Trollor, J., Tzourio, C., Van der Grond, J., Vernooij, M.W., Witte, V.A., Wright, M.J., Yang, Q., Morris, Z., Siggurdsson, S., Psaty, B.M., Villringer, A., Schmidt, H., Håberg, A.K., van Duijn, C.M., Jukema, J.W., Dichgans, M., Sacco, R.L., Wright, C.B., Kremen, W.S., Becker, L.C., Thompson, P.M., Mosley, T.H., Wardlaw, J.M., Ikram, M.A., Adams, H.H.H., Seshadri, S., Sachdev, P.S., Smith, S.M., Launer, L., Longstreth, W.T., DeCarli, C., Schmidt, R., Fornage, M., Debette, S., Nyquist, P.A., Armstrong, N.J., Mather, K.A., Sargurupremraj, M., Knol, M.J., Malik, R., Satizabal, C.L., Yanek, L.R., Wen, W., Gudnason, V.G., Dueker, N.D., Elliott, L.T., Hofer, E., Bis, J., Jahanshad, N., Li, S., Logue, M.A., Luciano, M., Scholz, M., Smith, A.V., Trompet, S., Vojinovic, D., Xia, R., Alfaro-Almagro, F., Ames, D., Amin, N., Amouyel, P., Beiser, A.S., Brodaty, H., Deary, I.J., Fennema-Notestine, C., Gampawar, P.G., Gottesman, R., Griffanti, L., Jack, C.R., Jenkinson, M., Jiang, J., Kral, B.G., Kwok, J.B., Lampe, L., Liewald, D.C.M., Maillard, P., Marchini, J., Bastin, M.E., Mazoyer, B., Pirpamer, L., Romero, J.R., Roshchupkin, G.V., Schofield, P.R., Schroeter, M.L., Stott, D.J., Thalamuthu, A., Trollor, J., Tzourio, C., Van der Grond, J., Vernooij, M.W., Witte, V.A., Wright, M.J., Yang, Q., Morris, Z., Siggurdsson, S., Psaty, B.M., Villringer, A., Schmidt, H., Håberg, A.K., van Duijn, C.M., Jukema, J.W., Dichgans, M., Sacco, R.L., Wright, C.B., Kremen, W.S., Becker, L.C., Thompson, P.M., Mosley, T.H., Wardlaw, J.M., Ikram, M.A., Adams, H.H.H., Seshadri, S., Sachdev, P.S., Smith, S.M., Launer, L., Longstreth, W.T., DeCarli, C., Schmidt, R., Fornage, M., Debette, S., and Nyquist, P.A.
Abstract: Background and Purpose: Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings. Methods: Participants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC. Results: In the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 (NBEAL), 10q23.1 (TSPAN14/FAM231A), and 10q24.33 (SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 (NOS3) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype. Conclusions: Our study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was mo
Published: 2020

7. Cerebral Embolism and Procoagulant States

Author: Jacobs, B.S., primary, Sacco, R.L., additional, and Alter, M., additional
Published: 1998
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8. Clinical discriminators of lobar and deep hemorrhages: the Stroke Data Bank

Author: Massaro, A.R., Sacco, R.L., Mohr, J.P., Foulkes, M.A., Tatemichi, T.K., Price, T.R., Hier, D.B., and Wolf, P.A.
Subjects: Stroke (Disease) -- Physiological aspects, Stroke (Disease) -- Demographic aspects, Brain -- Hemorrhage, Health, Psychology and mental health
Abstract: The clinical symptoms of stroke may result from the infarction of brain tissue or from the occurrence of a hemorrhage within the brain itself. Prior to the development of modern imaging techniques, many brain hemorrhages were not recognized as such, and were diagnosed as infarctions based on the patient's symptoms. CT scanning and magnetic resonance imaging (MRI) now permit the clear distinction of infarction from primary hemorrhage. (Of course, some hemorrhage may also occur as a secondary consequence of infarction.) The Stroke Data Bank was organized as a large prospective study for the evaluation of stroke patients. Of the 1,805 patients in the data bank, 237 had parenchymous hemorrhage. (This is a hemorrhage within the brain substance itself, distinct from other cranial hemorrhages such as a subarachnoid hemorrhage resulting from an aneurysm.) Thirty-four of these hemorrhages were secondary, and 31 were in the brain stem or cerebellum. The remaining 172 may be divided into lobar hemorrhages, which lie within or just under the cerebral cortex, and deep hemorrhages, which affect the central gray matter. (The central gray matter, deep within the brain, includes the basal ganglia and the thalamus.) Severe headache was a more common symptom among the 65 patients with lobar hemorrhage. Motor deficits were more common among the 107 patients with deep hemorrhage. Hypertension, the most important risk factor for cerebral hemorrhage, was more common among the patients with deep hemorrhage. Many other clinical features, such as seizures, focal neurological deficits, and decreased consciousness or coma, were found with comparable frequency among the patients with lobar hemorrhage and those with deep hemorrhage. (Consumer Summary produced by Reliance Medical Information, Inc.)
Published: 1991

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

Author: Chauhan, G., Adams, H.H.H., Satizabal, C.L., Bis, J.C., Teumer, A., Sargurupremraj, M., Hofer, E., Trompet, S., Hilal, S., Smith, A.V., Jian, X.Q., Malik, R., Traylor, M., Pulit, S.L., Amouyel, P., Mazoyer, B., Zhu, Y.C., Kaffashian, S., Schilling, S., Beecham, G.W., Montine, T.J., Schellenberg, G.D., Kjartansson, O., Gudnason, V., Knopman, D.S., Griswold, M.E., Windham, B.G., Gottesman, R.F., Mosley, T.H., Schmidt, R., Saba, Y., Schmidt, H., Takeuchi, F., Yamaguchi, S., Nabika, T., Kato, N., Rajan, K.B., Aggarwal, N.T., Jager, P.L. de, Evans, D.A., Psaty, B.M., Rotter, J.I., Rice, K., Lopez, O.L., Liao, J.M., Chen, C., Cheng, C.Y., Wong, T.Y., Ikram, M.K., Lee, S.J. van der, Amin, N., Chouraki, V., DeStefano, A.L., Aparicio, H.J., Romero, J.R., Maillard, P., DeCarli, C., Wardlaw, J.M., Hernandez, M.D.V., Luciano, M., Liewald, D., Deary, I.J., Starr, J.M., Bastin, M.E., Maniega, S.M., Slagboom, P.E., Beekman, M., Deelen, J., Uh, H.W., Lemmens, R., Brodaty, H., Wright, M.J., Ames, D., Boncoraglio, G.B., Hopewell, J.C., Beecham, A.H., Blanton, S.H., Wright, C.B., Sacco, R.L., Wen, W., Thalamuthu, A., Armstrong, N.J., Chong, E., Schofield, P.R., Kwok, J.B., Grond, J. van der, Stott, D.J., Ford, I., Jukema, J.W., Vernooij, M.W., Hofman, A., Uitterlinden, A.G., Lugt, A. van der, Wittfeld, K., Grabe, H.J., Hosten, N., Sarnowski, B. von, Volker, U., Levi, C., Jimenez-Conde, J., Sharma, P., Sudlow, C.L.M., Rosand, J., Woo, D., Cole, J.W., Meschia, J.F., Slowik, A., Thijs, V., Lindgren, A., Melander, O., Grewal, R.P., Rundek, T., Rexrode, K., Rothwell, P.M., Arnett, D.K., Jern, C., Johnson, J.A., Benavente, O.R., Wasssertheil-Smoller, S., Lee, J.M., Wong, Q., Mitchell, B.D., Rich, S.S., McArdle, P.F., Geerlings, M.I., Graaf, Y. van der, Bakker, P.I.W. de, Asselbergs, F.W., Srikanth, V., Thomson, R., McWhirter, R., Moran, C., Callisaya, M., Phan, T., Rutten-Jacobs, L.C.A., Bevan, S., Tzourio, C., Mather, K.A., Sachdev, P.S., Duijn, C.M. van, Worrall, B.B., Dichgans, M., Kittner, S.J., Markus, H.S., Ikram, M.A., Fornage, M., Launer, L.J., Seshadri, S., Longstreth, W.T., Debette, S., Stroke Genetics Network SiGN, ISGC, METASTROKE, ADGC, and CHARGE Consortium
Subjects: Meta-analysis, Mendelian Randomization, Blood Pressure, Polymorphisms, Genome-wide Association, Silent, Insights, Small Vessel Disease, Matter Hyperintensity Volume, Ischemic Stroke, Doenças Cardio e Cérebro-vasculares
Abstract: Collaborators (845): Astrid M. Vicente Free PMC article:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369905/ Objective: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods: We 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. Results: The 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. Conclusion: In 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. info:eu-repo/semantics/publishedVersion
Published: 2019

10. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Author: Feigin, V.L. Nichols, E. Alam, T. Bannick, M.S. Beghi, E. Blake, N. Culpepper, W.J. Dorsey, E.R. Elbaz, A. Ellenbogen, R.G. Fisher, J.L. Fitzmaurice, C. Giussani, G. Glennie, L. James, S.L. Johnson, C.O. Kassebaum, N.J. Logroscino, G. Marin, B. Mountjoy-Venning, W.C. Nguyen, M. Ofori-Asenso, R. Patel, A.P. Piccininni, M. Roth, G.A. Steiner, T.J. Stovner, L.J. Szoeke, C.E.I. Theadom, A. Vollset, S.E. Wallin, M.T. Wright, C. Zunt, J.R. Abbasi, N. Abd-Allah, F. Abdelalim, A. Abdollahpour, I. Aboyans, V. Abraha, H.N. Acharya, D. Adamu, A.A. Adebayo, O.M. Adeoye, A.M. Adsuar, J.C. Afarideh, M. Agrawal, S. Ahmadi, A. Ahmed, M.B. Aichour, A.N. Aichour, I. Aichour, M.T.E. Akinyemi, R.O. Akseer, N. Al-Eyadhy, A. Al-Shahi Salman, R. Alahdab, F. Alene, K.A. Aljunid, S.M. Altirkawi, K. Alvis-Guzman, N. Anber, N.H. Antonio, C.A.T. Arabloo, J. Aremu, O. Ärnlöv, J. Asayesh, H. Asghar, R.J. Atalay, H.T. Awasthi, A. Ayala Quintanilla, B.P. Ayuk, T.B. Badawi, A. Banach, M. Banoub, J.A.M. Barboza, M.A. Barker-Collo, S.L. Bärnighausen, T.W. Baune, B.T. Bedi, N. Behzadifar, M. Behzadifar, M. Béjot, Y. Bekele, B.B. Belachew, A.B. Bennett, D.A. Bensenor, I.M. Berhane, A. Beuran, M. Bhattacharyya, K. Bhutta, Z.A. Biadgo, B. Bijani, A. Bililign, N. Bin Sayeed, M.S. Blazes, C.K. Brayne, C. Butt, Z.A. Campos-Nonato, I.R. Cantu-Brito, C. Car, M. Cárdenas, R. Carrero, J.J. Carvalho, F. Castañeda-Orjuela, C.A. Castro, F. Catalá-López, F. Cerin, E. Chaiah, Y. Chang, J.-C. Chatziralli, I. Chiang, P.P.-C. Christensen, H. Christopher, D.J. Cooper, C. Cortesi, P.A. Costa, V.M. Criqui, M.H. Crowe, C.S. Damasceno, A.A.M. Daryani, A. De la Cruz-Góngora, V. De La Hoz, F.P. De Leo, D. Degefa, M.G. Demoz, G.T. Deribe, K. Dharmaratne, S.D. Diaz, D. Dinberu, M.T. Djalalinia, S. Doku, D.T. Dubey, M. Dubljanin, E. Duken, E.E. Edvardsson, D. El-Khatib, Z. Endres, M. Endries, A.Y. Eskandarieh, S. Esteghamati, A. Esteghamati, S. Farhadi, F. Faro, A. Farzadfar, F. Farzaei, M.H. Fatima, B. Fereshtehnejad, S.-M. Fernandes, E. Feyissa, G.T. Filip, I. Fischer, F. Fukumoto, T. Ganji, M. Gankpe, F.G. Garcia-Gordillo, M.A. Gebre, A.K. Gebremichael, T.G. Gelaw, B.K. Geleijnse, J.M. Geremew, D. Gezae, K.E. Ghasemi-Kasman, M. Gidey, M.Y. Gill, P.S. Gill, T.K. Gnedovskaya, E.V. Goulart, A.C. Grada, A. Grosso, G. Guo, Y. Gupta, R. Gupta, R. Haagsma, J.A. Hagos, T.B. Haj-Mirzaian, A. Haj-Mirzaian, A. Hamadeh, R.R. Hamidi, S. Hankey, G.J. Hao, Y. Haro, J.M. Hassankhani, H. Hassen, H.Y. Havmoeller, R. Hay, S.I. Hegazy, M.I. Heidari, B. Henok, A. Heydarpour, F. Hoang, C.L. Hole, M.K. Homaie Rad, E. Hosseini, S.M. Hu, G. Igumbor, E.U. Ilesanmi, O.S. Irvani, S.S.N. Islam, S.M.S. Jakovljevic, M. Javanbakht, M. Jha, R.P. Jobanputra, Y.B. Jonas, J.B. Józwiak, J.J. Jürisson, M. Kahsay, A. Kalani, R. Kalkonde, Y. Kamil, T.A. Kanchan, T. Karami, M. Karch, A. Karimi, N. Kasaeian, A. Kassa, T.D. Kassa, Z.Y. Kaul, A. Kefale, A.T. Keiyoro, P.N. Khader, Y.S. Khafaie, M.A. Khalil, I.A. Khan, E.A. Khang, Y.-H. Khazaie, H. Kiadaliri, A.A. Kiirithio, D.N. Kim, A.S. Kim, D. Kim, Y.-E. Kim, Y.J. Kisa, A. Kokubo, Y. Koyanagi, A. Krishnamurthi, R.V. Kuate Defo, B. Kucuk Bicer, B. Kumar, M. Lacey, B. Lafranconi, A. Lansingh, V.C. Latifi, A. Leshargie, C.T. Li, S. Liao, Y. Linn, S. Lo, W.D. Lopez, J.C.F. Lorkowski, S. Lotufo, P.A. Lucas, R.M. Lunevicius, R. Mackay, M.T. Mahotra, N.B. Majdan, M. Majdzadeh, R. Majeed, A. Malekzadeh, R. Malta, D.C. Manafi, N. Mansournia, M.A. Mantovani, L.G. März, W. Mashamba-Thompson, T.P. Massenburg, B.B. Mate, K.K.V. McAlinden, C. McGrath, J.J. Mehta, V. Meier, T. Meles, H.G. Melese, A. Memiah, P.T.N. Memish, Z.A. Mendoza, W. Mengistu, D.T. Mengistu, G. Meretoja, A. Meretoja, T.J. Mestrovic, T. Miazgowski, B. Miazgowski, T. Miller, T.R. Mini, G.K. Mirrakhimov, E.M. Moazen, B. Mohajer, B. Mohammad Gholi Mezerji, N. Mohammadi, M. Mohammadi-Khanaposhtani, M. Mohammadibakhsh, R. Mohammadnia-Afrouzi, M. Mohammed, S. Mohebi, F. Mokdad, A.H. Monasta, L. Mondello, S. Moodley, Y. Moosazadeh, M. Moradi, G. Moradi-Lakeh, M. Moradinazar, M. Moraga, P. Moreno Velásquez, I. Morrison, S.D. Mousavi, S.M. Muhammed, O.S. Muruet, W. Musa, K.I. Mustafa, G. Naderi, M. Nagel, G. Naheed, A. Naik, G. Najafi, F. Nangia, V. Negoi, I. Negoi, R.I. Newton, C.R.J. Ngunjiri, J.W. Nguyen, C.T. Nguyen, L.H. Ningrum, D.N.A. Nirayo, Y.L. Nixon, M.R. Norrving, B. Noubiap, J.J. Nourollahpour Shiadeh, M. Nyasulu, P.S. Ogbo, F.A. Oh, I.-H. Olagunju, A.T. Olagunju, T.O. Olivares, P.R. Onwujekwe, O.E. Oren, E. Owolabi, M.O. A, M.P. Pakpour, A.H. Pan, W.-H. Panda-Jonas, S. Pandian, J.D. Patel, S.K. Pereira, D.M. Petzold, M. Pillay, J.D. Piradov, M.A. Polanczyk, G.V. Polinder, S. Postma, M.J. Poulton, R. Poustchi, H. Prakash, S. Prakash, V. Qorbani, M. Radfar, A. Rafay, A. Rafiei, A. Rahim, F. Rahimi-Movaghar, V. Rahman, M. Rahman, M.H.U. Rahman, M.A. Rajati, F. Ram, U. Ranta, A. Rawaf, D.L. Rawaf, S. Reinig, N. Reis, C. Renzaho, A.M.N. Resnikoff, S. Rezaeian, S. Rezai, M.S. Rios González, C.M. Roberts, N.L.S. Roever, L. Ronfani, L. Roro, E.M. Roshandel, G. Rostami, A. Sabbagh, P. Sacco, R.L. Sachdev, P.S. Saddik, B. Safari, H. Safari-Faramani, R. Safi, S. Safiri, S. Sagar, R. Sahathevan, R. Sahebkar, A. Sahraian, M.A. Salamati, P. Salehi Zahabi, S. Salimi, Y. Samy, A.M. Sanabria, J. Santos, I.S. Santric Milicevic, M.M. Sarrafzadegan, N. Sartorius, B. Sarvi, S. Sathian, B. Satpathy, M. Sawant, A.R. Sawhney, M. Schneider, I.J.C. Schöttker, B. Schwebel, D.C. Seedat, S. Sepanlou, S.G. Shabaninejad, H. Shafieesabet, A. Shaikh, M.A. Shakir, R.A. Shams-Beyranvand, M. Shamsizadeh, M. Sharif, M. Sharif-Alhoseini, M. She, J. Sheikh, A. Sheth, K.N. Shigematsu, M. Shiri, R. Shirkoohi, R. Shiue, I. Siabani, S. Siddiqi, T.J. Sigfusdottir, I.D. Sigurvinsdottir, R. Silberberg, D.H. Silva, J.P. Silveira, D.G.A. Singh, J.A. Sinha, D.N. Skiadaresi, E. Smith, M. Sobaih, B.H. Sobhani, S. Soofi, M. Soyiri, I.N. Sposato, L.A. Stein, D.J. Stein, M.B. Stokes, M.A. Sufiyan, M.B. Sykes, B.L. Sylaja, P. Tabarés-Seisdedos, R. Te Ao, B.J. Tehrani-Banihashemi, A. Temsah, M.-H. Temsah, O. Thakur, J.S. Thrift, A.G. Topor-Madry, R. Tortajada-Girbés, M. Tovani-Palone, M.R. Tran, B.X. Tran, K.B. Truelsen, T.C. Tsadik, A.G. Tudor Car, L. Ukwaja, K.N. Ullah, I. Usman, M.S. Uthman, O.A. Valdez, P.R. Vasankari, T.J. Vasanthan, R. Veisani, Y. Venketasubramanian, N. Violante, F.S. Vlassov, V. Vosoughi, K. Vu, G.T. Vujcic, I.S. Wagnew, F.S. Waheed, Y. Wang, Y.-P. Weiderpass, E. Weiss, J. Whiteford, H.A. Wijeratne, T. Winkler, A.S. Wiysonge, C.S. Wolfe, C.D.A. Xu, G. Yadollahpour, A. Yamada, T. Yano, Y. Yaseri, M. Yatsuya, H. Yimer, E.M. Yip, P. Yisma, E. Yonemoto, N. Yousefifard, M. Yu, C. Zaidi, Z. Zaman, S.B. Zamani, M. Zandian, H. Zare, Z. Zhang, Y. Zodpey, S. Naghavi, M. Murray, C.J.L. Vos, T. GBD 2016 Neurology Collaborators
Abstract: Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach. Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable). Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. Funding: Bill & Melinda Gates Foundation. © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Published: 2019

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

Author: Aparicio H.J., Del C. Valdes Hernandez M., Luciano M., Liewald D., Deary I.J., Starr J.M., Bastin M.E., Maniega S.M., Slagboom P.E., Beekman M., Deelen J., Uh H.-W., Lemmens R., Brodaty H., Wright M.J., Ames D., Boncoraglio G.B., Hopewell J.C., Beecham A.H., Blanton S.H., Wright C.B., Sacco R.L., Wen W., Thalamuthu A., Armstrong N.J., Chong E., Schofield P.R., Kwok J.B., van der Grond J., Stott D.J., Ford I., Jukema J.W., Vernooij M.W., Hofman A., Uitterlinden A.G., van der Lugt A., Wittfeld K., Grabe H.J., Hosten N., von Sarnowski B., Volker U., Levi C., Jimenez-Conde J., Sharma P., Sudlow C.L.M., Rosand J., Woo D., Cole J.W., Meschia J.F., Slowik A., Thijs V., Lindgren A., Melander O., Grewal R.P., Rundek T., Rexrode K., Rothwell P.M., Arnett D.K., Jern C., Johnson J.A., Benavente O.R., Wasssertheil-Smoller S., Lee J.-M., Wong Q., Mitchell B.D., Rich S.S., McArdle P.F., Geerlings M.I., van der Graaf Y., de Bakker P.I.W., Asselbergs F.W., Srikanth V., Thomson R., McWhirter R., Moran C., Callisaya M., Phan T., Rutten-Jacobs L.C.A., Bevan S., Tzourio C., Mather K.A., Sachdev P.S., van Duijn C.M., Worrall B.B., Dichgans M., Kittner S.J., Markus H.S., Ikram M.A., Fornage M., Launer L.J., Seshadri S., Longstreth W.T., Debette S., Chauhan G., Adams H.H.H., Satizabal C.L., Bis J.C., Teumer A., Sargurupremraj M., Hofer E., Trompet S., Hilal S., Smith A.V., Jian X., Malik R., Traylor M., Pulit S.L., Amouyel P., Mazoyer B., Zhu Y.-C., Kaffashian S., Schilling S., Beecham G.W., Montine T.J., Schellenberg G.D., Kjartansson O., Gudnason V., Knopman D.S., Griswold M.E., Windham B.G., Gottesman R.F., Mosley T.H., Schmidt R., Saba Y., Schmidt H., Takeuchi F., Yamaguchi S., Nabika T., Kato N., Rajan K.B., Aggarwal N.T., De Jager P.L., Evans D.A., Psaty B.M., Rotter J.I., Rice K., Lopez O.L., Liao J., Chen C., Cheng C.-Y., Wong T.Y., Ikram M.K., van der Lee S.J., Amin N., Chouraki V., Destefano A.L., Romero J.R., Maillard P., Decarli C., Wardlaw J.M., Aparicio H.J., Del C. Valdes Hernandez M., Luciano M., Liewald D., Deary I.J., Starr J.M., Bastin M.E., Maniega S.M., Slagboom P.E., Beekman M., Deelen J., Uh H.-W., Lemmens R., Brodaty H., Wright M.J., Ames D., Boncoraglio G.B., Hopewell J.C., Beecham A.H., Blanton S.H., Wright C.B., Sacco R.L., Wen W., Thalamuthu A., Armstrong N.J., Chong E., Schofield P.R., Kwok J.B., van der Grond J., Stott D.J., Ford I., Jukema J.W., Vernooij M.W., Hofman A., Uitterlinden A.G., van der Lugt A., Wittfeld K., Grabe H.J., Hosten N., von Sarnowski B., Volker U., Levi C., Jimenez-Conde J., Sharma P., Sudlow C.L.M., Rosand J., Woo D., Cole J.W., Meschia J.F., Slowik A., Thijs V., Lindgren A., Melander O., Grewal R.P., Rundek T., Rexrode K., Rothwell P.M., Arnett D.K., Jern C., Johnson J.A., Benavente O.R., Wasssertheil-Smoller S., Lee J.-M., Wong Q., Mitchell B.D., Rich S.S., McArdle P.F., Geerlings M.I., van der Graaf Y., de Bakker P.I.W., Asselbergs F.W., Srikanth V., Thomson R., McWhirter R., Moran C., Callisaya M., Phan T., Rutten-Jacobs L.C.A., Bevan S., Tzourio C., Mather K.A., Sachdev P.S., van Duijn C.M., Worrall B.B., Dichgans M., Kittner S.J., Markus H.S., Ikram M.A., Fornage M., Launer L.J., Seshadri S., Longstreth W.T., Debette S., Chauhan G., Adams H.H.H., Satizabal C.L., Bis J.C., Teumer A., Sargurupremraj M., Hofer E., Trompet S., Hilal S., Smith A.V., Jian X., Malik R., Traylor M., Pulit S.L., Amouyel P., Mazoyer B., Zhu Y.-C., Kaffashian S., Schilling S., Beecham G.W., Montine T.J., Schellenberg G.D., Kjartansson O., Gudnason V., Knopman D.S., Griswold M.E., Windham B.G., Gottesman R.F., Mosley T.H., Schmidt R., Saba Y., Schmidt H., Takeuchi F., Yamaguchi S., Nabika T., Kato N., Rajan K.B., Aggarwal N.T., De Jager P.L., Evans D.A., Psaty B.M., Rotter J.I., Rice K., Lopez O.L., Liao J., Chen C., Cheng C.-Y., Wong T.Y., Ikram M.K., van der Lee S.J., Amin N., Chouraki V., Destefano A.L., Romero J.R., Maillard P., Decarli C., and Wardlaw J.M.
Abstract: Objective To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods We 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. Results The 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 x 10-8; and LINC00539/ZDHHC20, p = 5.82 x 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 x 10-25; p [SSBI] = 5.23 x 10-14 for hypertension), smoking (p[BI]= 4.4 x 10-10; p [SSBI] = 1.2 x 10 -4), diabetes (p[BI] = 1.7 x 10 -8; p [SSBI] = 2.8 x 10 -3), previous cardiovascular disease (p [BI] = 1.0 x 10-18; p [SSBI] = 2.3 x 10-7), stroke (p [BI] = 3.9 x 10-69; p [SSBI] = 3.2 x 10 -24), and MRI-defined white matter hyperintensity burden (p [BI]=1.43 x 10-157; p [SSBI] = 3.16 x 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. Conclusion In 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 significa
Published: 2019

12. Antiplatelet Therapy After Noncardioembolic Stroke An Individual Patient Data Network Meta-Analysis

Author: Greving, J.P. (Jacoba), Diener, H.C. (Hans Christoph), Reitsma, J.B. (Johannes), Bath, P.M., Csiba, L., Hacke, W. (Werner), Kappelle, L.J. (Jaap), Koudstaal, P.J. (Peter), Leys, D., Mas, J.L., Sacco, R.L. (Ralph), Algra, A. (Ale), Greving, J.P. (Jacoba), Diener, H.C. (Hans Christoph), Reitsma, J.B. (Johannes), Bath, P.M., Csiba, L., Hacke, W. (Werner), Kappelle, L.J. (Jaap), Koudstaal, P.J. (Peter), Leys, D., Mas, J.L., Sacco, R.L. (Ralph), and Algra, A. (Ale)
Abstract: Background and Purpose— We assessed the efficacy and safety of antiplatelet agents after noncardioembolic stroke or transient ischemic attack and examined how these vary according to patients’ demographic and clinical characteristics. Methods— We did a network meta-analysis (NMA) of data from 6 randomized trials of the effects of commonly prescribed antiplatelet agents in the long-term (≥3 months) secondary prevention of noncardioembolic stroke or transient ischemic attack. Individual patient data from 43 112 patients were pooled and reanalyzed. Main outcomes were serious vascular events (nonfatal stroke, nonfatal myocardial infarction, or vascular death), major bleeding, and net clinical benefit (serious vascular event or major bleeding). Subgroup analyses were done according to age, sex, ethnicity, hypertension, qualifying diagnosis, type of vessel involved (large versus small vessel disease), and time from qualifying event to randomization. Results— Aspirin/dipyridamole combination (RRNMA-adj, 0.83; 95% CI, 0.74–0.94) significantly reduced the risk of vascular events compared with aspirin, as did clopidogrel (RRNMA-adj, 0.88; 95% CI, 0.78–0.98), and aspirin/clopidogrel combination (RRNMA-adj, 0.83; 95% CI, 0.71–0.96). Clopidogrel caused significantly less major bleeding and intracranial hemorrhage than aspirin, aspirin/dipyridamole combination, and aspirin/clopidogrel combination. Aspirin/clopidogrel combination caused significantly more major bleeding than aspirin, aspirin/dipyridamole combination, and clopidogrel. Net clinical benefit was similar for clopidogrel and aspirin/dipyridamole combination (RRNMA-adj, 0.99; 95% CI, 0.93–1.05). Subgroup analyses showed no heterogeneity of treatment effectiveness across prespecified subgroups. The excess risk of major bleeding associated with aspirin/clopidogrel combination compared with clopidogrel alone was higher in patients aged <65 years than it was in patients ≥65 years (RRNMA-adj, 3.9 versus 1.7). Conclusions— Res
Published: 2019
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13. Re-spect Esus : Dabigratan versus acetylsalicylic acid for stroke prevention in patients with embolic stroke of undetermined source

Author: Diener, Hans Christoph, Sacco, R.L., Easton, J.D., Granger, C.B., Cronin, L., Grauer, C., Cotton, D., and Brueckmann, M.
Subjects: Medizin
Published: 2018

14. Brain Perivascular Spaces as Biomarkers of Vascular Risk: Results from the Northern Manhattan Study

Author: Gutierrez, J., primary, Elkind, M.S.V., additional, Dong, C., additional, Di Tullio, M., additional, Rundek, T., additional, Sacco, R.L., additional, and Wright, C.B., additional
Published: 2017
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15. Genetic variation at 16q24.2 is associated with small vessel stroke

Author: Traylor, M. (Matthew), Malik, R. (Rainer), Nalls, M.A. (Michael), Cotlarciuc, I. (Ioana), Radmanesh, F. (Farid), Thorleifsson, G. (Gudmar), Hanscombe, K.B. (Ken B.), Langefeld, C.D. (Carl), Saleheen, D. (Danish), Rost, N.S. (Natalia), Yet, I. (Idil), Spector, T.D. (Timothy), Bell, J.T. (Jordana), Hannon, E. (Eilis), Mill, J. (Jonathan), Chauhan, G. (Ganesh), Debette, S. (Stéphanie), Bis, J.C. (Joshua), Longstreth Jr, W.T., Ikram, M.K. (Kamran), Launer, L.J. (Lenore), Seshadri, S. (Sudha), Hamilton-Bruce, M.A. (Monica Anne), Jimenez-Conde, J. (Jordi), Cole, J.W. (John W.), Schmidt, R. (Reinhold), Slowik, A. (Agnieszka), Lemmens, R. (Robin), Lindgren, A.G. (Arne G.), Melander, O. (Olle), Grewal, R.P. (Raji P.), Sacco, R.L. (Ralph), Rundek, T. (Tatjana), Rexrode, K. (Kathryn), Arnett, D.K. (Donna), Johnson, J.A. (Julie A.), Benavente, O.R. (Oscar R.), Wasssertheil-Smoller, S. (Sylvia), Lee, J.-M. (Jin-Moo), Pulit, S.L. (Sara), Wong, Q. (Quenna), Rich, S.S. (Stephen), Bakker, P.I.W. (Paul) de, McArdle, P.F. (Patrick), Woo, D. (Daniel), Anderson, C.D. (Christopher D.), Xu, H. (Huichun), Heitsch, L. (Laura), Fornage, M. (Myriam), Jern, C. (Christina), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Gretarsdottir, S. (Solveig), Lewis, C.M. (Cathryn), Sharma, P. (Pankaj), Sudlow, C. (Cathie), Rothwell, P.M. (Peter), Boncoraglio, G. (Giorgio Battista), Thijs, V. (Vincent), Levi, C. (Christopher), Meschia, J.F. (James F.), Rosand, J. (Jonathan), Kittner, T. (Thomas), Mitchell, B.D. (Braxton), Kubisch, C. (Christian), Worrall, B.B. (Bradford B.), Markus, H.S. (Hugh), Traylor, M. (Matthew), Malik, R. (Rainer), Nalls, M.A. (Michael), Cotlarciuc, I. (Ioana), Radmanesh, F. (Farid), Thorleifsson, G. (Gudmar), Hanscombe, K.B. (Ken B.), Langefeld, C.D. (Carl), Saleheen, D. (Danish), Rost, N.S. (Natalia), Yet, I. (Idil), Spector, T.D. (Timothy), Bell, J.T. (Jordana), Hannon, E. (Eilis), Mill, J. (Jonathan), Chauhan, G. (Ganesh), Debette, S. (Stéphanie), Bis, J.C. (Joshua), Longstreth Jr, W.T., Ikram, M.K. (Kamran), Launer, L.J. (Lenore), Seshadri, S. (Sudha), Hamilton-Bruce, M.A. (Monica Anne), Jimenez-Conde, J. (Jordi), Cole, J.W. (John W.), Schmidt, R. (Reinhold), Slowik, A. (Agnieszka), Lemmens, R. (Robin), Lindgren, A.G. (Arne G.), Melander, O. (Olle), Grewal, R.P. (Raji P.), Sacco, R.L. (Ralph), Rundek, T. (Tatjana), Rexrode, K. (Kathryn), Arnett, D.K. (Donna), Johnson, J.A. (Julie A.), Benavente, O.R. (Oscar R.), Wasssertheil-Smoller, S. (Sylvia), Lee, J.-M. (Jin-Moo), Pulit, S.L. (Sara), Wong, Q. (Quenna), Rich, S.S. (Stephen), Bakker, P.I.W. (Paul) de, McArdle, P.F. (Patrick), Woo, D. (Daniel), Anderson, C.D. (Christopher D.), Xu, H. (Huichun), Heitsch, L. (Laura), Fornage, M. (Myriam), Jern, C. (Christina), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Gretarsdottir, S. (Solveig), Lewis, C.M. (Cathryn), Sharma, P. (Pankaj), Sudlow, C. (Cathie), Rothwell, P.M. (Peter), Boncoraglio, G. (Giorgio Battista), Thijs, V. (Vincent), Levi, C. (Christopher), Meschia, J.F. (James F.), Rosand, J. (Jonathan), Kittner, T. (Thomas), Mitchell, B.D. (Braxton), Kubisch, C. (Christian), Worrall, B.B. (Bradford B.), and Markus, H.S. (Hugh)
Abstract: Objective: Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises one quarter of all ischemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown that younger-onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger-onset SVS population, to identify novel associations with stroke. Methods: We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated with stroke. On identifying a novel locus associated with SVS, we assessed its influence on other small vessel disease phenotypes, as well as on messenger RNA (mRNA) expression of nearby genes, and on DNA methylation of nearby CpG sites in whole blood and in the fetal brain. Results: We identified an association with SVS in 4,203 cases and 50,728 controls on chromosome 16q24.2 (odds ratio [OR; 95% confidence interval {CI}] = 1.16 [1.10–1.22]; p = 3.2 × 10−9). The lead single-nucleotide polymorphism (rs12445022) was also associated with cerebral white matter hyperintensities (OR [95% CI] = 1.10 [1.05–1.16]; p = 5.3 × 10−5; N = 3,670), but not intracerebral hemorrhage (OR [95% CI] = 0.97 [0.84–1.12]; p = 0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p = 9.4 × 10−7) and DNA methylation at probe cg16596957
Published: 2017
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16. Automatic identification of variables in epidemiological datasets using logic regression

Author: Lorenz, M.W. (Matthias W.), Abdi, N.A. (Negin Ashtiani), Scheckenbach, F. (Frank), Pflug, A. (Anja), Bulbul, A. (Alpaslan), Catapano, A.L. (Alberico), Agewall, S. (Stefan), Ezhov, M. (Marat), Bots, M.L. (Michiel), Kiechl, S. (Stefan), Orth, A. (Andreas), Norata, G.D. (Giuseppe), Empana, J.P. (Jean Philippe), Lin, H.-J. (Hung-Ju), McLachlan, S. (Stela), Bokemark, L. (Lena), Ronkainen, K. (Kimmo), Amato, M. (Mauro), Schminke, U. (Ulf), Srinivasan, S.R. (Sathanur R.), Lind, L. (Lars), Kato, A. (Akihiko), Dimitriadis, C. (Chrystosomos), Przewlocki, T. (Tadeusz), Okazaki, S. (Shuhei), Stehouwer, C.D. (Coen), Lazarevic, T. (Tatjana), Willeit, J. (Johann), Yanez, D.N. (David N.), Steinmetz, H. (helmuth), Sander, D. (Dirk), Poppert, H. (Holger), Desvarieux, M. (Moise), Ikram, M.A. (Arfan), Bevc, S. (Sebastjan), Staub, D. (Daniel), Sirtori, C.R. (Cesare R.), Iglseder, B. (Bernhard), Engström, G., Tripepi, G.L. (Giovanni), Beloqui, O. (Oscar), Lee, M.-S. (Moo-Sik), Friera, A. (Alfonsa), Xie, W. (Wuxiang), Grigore, L. (Liliana), Plichart, M. (Matthieu), Su, T.-C. (Ta-Chen), Robertson, C.M. (Christine M), Schmidt, C. (Caroline), Tuomainen, T.-P. (Tomi-Pekka), Veglia, F. (Fabrizio), Völzke, H. (Henry), Nijpels, M.G.A.A.M. (Giel), Jovanovic, A. (Aleksandar), Sacco, R.L. (Ralph L.), Franco, O.H. (Oscar), Hojs, R. (Radovan), Uthoff, H. (Heiko), Hedblad, B. (Bo), Park, H.W. (Hyun Woong), Suarez, C. (Carmen), Zhao, D. (Dong), Catapano, A. (Alberico), Ducimetiere, P. (P.), Chien, K.-L. (Kuo-Liong), Price, J.F. (Jackie F.), Bergstrom, G. (Goran), Kauhanen, J. (Jussi), Tremoli, E. (Elena), Dörr, M. (Marcus), Berenson, G. (Gerald), Papagianni, A. (Aikaterini), Kablak-Ziembicka, A. (Anna), Kitagawa, K. (Kazuo), Dekker, J.M. (Jacqueline), Stolic, R. (Radojica), Polak, J.F. (Joseph F.), Sitzer, M. (Matthias), Bickel, H. (Horst), Rundek, T. (Tatjana), Hofman, A. (Albert), Ekart, R. (Robert), Frauchiger, B. (Beat), Castelnuovo, S. (Samuela), Rosvall, M. (Maria), Zoccali, C. (Carmine), Landecho, M.F. (Manuel F.), Bae, J.-H. (Jang-Ho), Gabriel, R. (Rafael), Liu, J. (Jing), Baldassarre, D. (Damiano), Kavousi, M. (Maryam), Lorenz, M.W. (Matthias W.), Abdi, N.A. (Negin Ashtiani), Scheckenbach, F. (Frank), Pflug, A. (Anja), Bulbul, A. (Alpaslan), Catapano, A.L. (Alberico), Agewall, S. (Stefan), Ezhov, M. (Marat), Bots, M.L. (Michiel), Kiechl, S. (Stefan), Orth, A. (Andreas), Norata, G.D. (Giuseppe), Empana, J.P. (Jean Philippe), Lin, H.-J. (Hung-Ju), McLachlan, S. (Stela), Bokemark, L. (Lena), Ronkainen, K. (Kimmo), Amato, M. (Mauro), Schminke, U. (Ulf), Srinivasan, S.R. (Sathanur R.), Lind, L. (Lars), Kato, A. (Akihiko), Dimitriadis, C. (Chrystosomos), Przewlocki, T. (Tadeusz), Okazaki, S. (Shuhei), Stehouwer, C.D. (Coen), Lazarevic, T. (Tatjana), Willeit, J. (Johann), Yanez, D.N. (David N.), Steinmetz, H. (helmuth), Sander, D. (Dirk), Poppert, H. (Holger), Desvarieux, M. (Moise), Ikram, M.A. (Arfan), Bevc, S. (Sebastjan), Staub, D. (Daniel), Sirtori, C.R. (Cesare R.), Iglseder, B. (Bernhard), Engström, G., Tripepi, G.L. (Giovanni), Beloqui, O. (Oscar), Lee, M.-S. (Moo-Sik), Friera, A. (Alfonsa), Xie, W. (Wuxiang), Grigore, L. (Liliana), Plichart, M. (Matthieu), Su, T.-C. (Ta-Chen), Robertson, C.M. (Christine M), Schmidt, C. (Caroline), Tuomainen, T.-P. (Tomi-Pekka), Veglia, F. (Fabrizio), Völzke, H. (Henry), Nijpels, M.G.A.A.M. (Giel), Jovanovic, A. (Aleksandar), Sacco, R.L. (Ralph L.), Franco, O.H. (Oscar), Hojs, R. (Radovan), Uthoff, H. (Heiko), Hedblad, B. (Bo), Park, H.W. (Hyun Woong), Suarez, C. (Carmen), Zhao, D. (Dong), Catapano, A. (Alberico), Ducimetiere, P. (P.), Chien, K.-L. (Kuo-Liong), Price, J.F. (Jackie F.), Bergstrom, G. (Goran), Kauhanen, J. (Jussi), Tremoli, E. (Elena), Dörr, M. (Marcus), Berenson, G. (Gerald), Papagianni, A. (Aikaterini), Kablak-Ziembicka, A. (Anna), Kitagawa, K. (Kazuo), Dekker, J.M. (Jacqueline), Stolic, R. (Radojica), Polak, J.F. (Joseph F.), Sitzer, M. (Matthias), Bickel, H. (Horst), Rundek, T. (Tatjana), Hofman, A. (Albert), Ekart, R. (Robert), Frauchiger, B. (Beat), Castelnuovo, S. (Samuela), Rosvall, M. (Maria), Zoccali, C. (Carmine), Landecho, M.F. (Manuel F.), Bae, J.-H. (Jang-Ho), Gabriel, R. (Rafael), Liu, J. (Jing), Baldassarre, D. (Damiano), and Kavousi, M. (Maryam)
Abstract: Background: For an individual participant data (IPD) meta-analysis, multiple datasets must be transformed in a consistent format, e.g. using uniform variable names. When large numbers of datasets have to be processed, this can be a time-consuming and error-prone task. Automated or semi-automated identification of variables can help to reduce the workload and improve the data quality. For semi-automation high sensitivity in the recognition of matching variables is particularly important, because it allows creating software which for a target variable presents a choice of source variables, from which a user can choose the matching one, with only low risk of having missed a correct source variable. Methods: For each variable in a set of target variables, a number of simple rules were manually created. With logic regression, an optimal Boolean combination of these rules was searched for every target variable, using a random subset of a large database of epidemiological and clinical cohort data (construction subset). In a second subset of this database (validation subset), this optimal combination rules were validated. Results: In the construction sample, 41 target variables were allocated on average with a positive predictive value (PPV) of 34%, and a negative predictive value (NPV) of 95%. In the validation sample, PPV was 33%, whereas NPV remained at 94%. In the construction sample, PPV was 50% or less in 63% of all variables, in the validation sample in 71% of all variables. Conclusions: We demonstrated that the application of logic regression in a complex data management task in large epidemiological IPD meta-analyses is feasible. However, the performance of the algorithm is poor, which may require backup strategies.
Published: 2017
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17. Novel genetic loci associated with hippocampal volume

Author: Hibar, D.P. (Derrek), Adams, H.H.H. (Hieab), Jahanshad, N. (Neda), Chauhan, G. (Ganesh), Stein, J.L., Hofer, E. (Edith), Rentería, M.E. (Miguel), Bis, J.C. (Joshua), Arias-Vásquez, A. (Alejandro), Ikram, M.K. (M. Kamran), Desrivières, S. (Sylvane), Vernooij, M.W. (Meike), Abramovic, L. (Lucija), Alhusaini, S. (Saud), Amin, N. (Najaf), Andersson, M. (Micael), Arfanakis, K. (Konstantinos), Aribisala, B. (Benjamin), Armstrong, N.J. (Nicola J.), Athanasiu, L. (Lavinia), Axelsson, T. (Tomas), Beecham, A.H. (Ashley), Beiser, A. (Alexa), Bernard, M. (Manon), Blanton, S.H. (Susan H.), Bohlken, M.M. (Marc M.), Boks, M.P.M. (Marco), Bralten, L.B.C. (Linda), Brickman, A.M. (Adam M.), Carmichael, O. (Owen), Chakravarty, M.M. (M. Mallar), Chen, Q. (Qiang), Ching, C.R.K. (Christopher), Chouraki, V. (Vincent), Cuellar-Partida, G. (Gabriel), Crivello, F. (Fabrice), Braber, A. (Anouk) den, Doan, N.T. (Nhat Trung), Ehrlich, S.M. (Stefan), Giddaluru, S. (Sudheer), Goldman, A.L. (Aaron L.), Gottesman, R.F. (Rebecca), Grimm, O. (Oliver), Griswold, M.D. (Michael), Guadalupe, T. (Tulio), Gutman, B.A. (Boris A.), Hass, J. (Johanna), Haukvik, U.K. (Unn), Hoehn, D. (David), Holmes, A.J. (Avram), Hoogman, M. (Martine), Janowitz, D. (Deborah), Jia, T. (Tianye), Jørgensen, K.N. (Kjetil N.), Karbalai, N. (Nazanin), Kasperaviciute, D. (Dalia), Kim, S. (Shinseog), Klein, M. (Marieke), Kraemer, B. (Bernd), Lee, P.H. (Phil), Liewald, D.C.M. (David), Lopez, L.M. (Lorna), Luciano, M. (Michelle), MacAre, C. (Christine), Marquand, A.F. (Andre F.), Matarin, M. (Mar), Mather, R., Mattheisen, M. (Manuel), McKay, D.R. (David R.), Milaneschi, Y. (Yuri), Muñoz Maniega, S. (Susana), Nho, K. (Kwangsik), Nugent, A.C. (Allison), Nyquist, P. (Paul), Loohuis, L.M.O. (Loes M. Olde), Oosterlaan, J. (Jaap), Papmeyer, M. (Martina), Pirpamer, L. (Lukas), Pütz, B. (Benno), Ramasamy, A. (Adaikalavan), Richards, J.S. (Jennifer S.), Risacher, S.L. (Shannon), Roiz-Santiañez, R. (Roberto), Rommelse, N. (Nanda), Ropele, S. (Stefan), Rose, E.J. (Emma), Royle, N.A. (Natalie), Rundek, T. (Tatjana), Sämann, P.G. (Philipp), Saremi, A. (Arvin), Satizabal, C.L. (Claudia), Schmaal, L. (Lianne), Schork, N.J. (Nicholas), Shen, L. (Li), Shin, J. (Jean), Shumskaya, E. (Elena), Smith, A.V. (Albert Vernon), Sprooten, R. (Roy), Strike, L.T. (Lachlan), Teumer, A. (Alexander), Tordesillas-Gutierrez, D. (Diana), Toro, R. (Roberto), Trabzuni, D. (Danyah), Trompet, S. (Stella), Vaidya, D. (Dhananjay), van der Grond, J. (Jeroen), Lee, S.J. (Sven) van der, Van Der Meer, D. (Dennis), Van Donkelaar, M.M.J. (Marjolein M. J.), Eijk, K.R. (Kristel) van, Erp, T.G.M. (Theo G.) van, Van Rooij, D. (Daan), Walton, E. (Esther), Westlye, L.T. (Lars), Whelan, C.D. (Christopher), Windham, B.G. (Gwen), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Woldehawariat, G. (Girma), Björnsson, A. (Asgeir), Wolfers, T. (Thomas), Yanek, L.R. (Lisa), Yang, J. (Jingyun), Zijdenbos, A.P., Zwiers, M.P. (Marcel), Agartz, I. (Ingrid), Almasy, L. (Laura), Ames, D.J. (David), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Arepalli, S. (Sampath), Assareh, A.A., Barral, S. (Sandra), Bastin, M.E. (Mark), Becker, D.M. (Diane M.), Becker, J.T. (James), Bennett, D.A. (David A.), Blangero, J. (John), Bokhoven, H. (Hans) van, Boomsma, D.I. (Dorret), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Brunner, H.G., Buckner, M., Buitelaar, J.K. (Jan), Bulayeva, K. (Kazima), Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D.M. (Dara), Cavalleri, G. (Gianpiero), Cheng, C.-Y. (Ching-Yu), Cichon, S. (Sven), Cookson, M.R. (Mark), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Curran, J.E. (Joanne), Czisch, M. (Michael), Dale, A.M. (Anders), Davies, G.E. (Gareth), Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Jager, P.L. (Philip) de, Zubicaray, G.I. (Greig) de, Deary, I.J. (Ian), Debette, S. (Stéphanie), DeCarli, C. (Charles), Delanty, N., Depondt, C. (Chantal), DeStefano, A.L. (Anita), Dillman, A. (Allissa), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drevets, D.A. (Douglas), Duggirala, R. (Ravi), Dyer, M.D. (Matthew), Enzinger, C. (Christian), Erk, S., Espeseth, T. (Thomas), Fedko, I.O. (Iryna O.), Fernández, G. (Guillén), Ferrucci, L. (Luigi), Fisher, S.E. (Simon), Fleischman, D. (Debra), Ford, I. (Ian), Fornage, M. (Myriam), Foroud, T. (Tatiana), Fox, P.T. (Peter), Francks, C. (Clyde), Fukunaga, M. (Masaki), Gibbs, J.R. (J. Raphael), Glahn, D.C. (David), Gollub, R.L. (Randy), Göring, H.H.H. (Harald H.), Green, R.C. (Robert C.), Gruber, O. (Oliver), Gudnason, V. (Vilmundur), Guelfi, S. (Sebastian), Håberg, A.K. (Asta K.), Hansell, N.K. (Narelle), Hardy, J. (John), Hartman, C.A. (C.), Hashimoto, R. (Ryota), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Le Hellard, S. (Stephanie), Hernandez, D.G. (Dena), Heslenfeld, D.J. (Dirk), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Holsboer, F. (Florian), Homuth, G. (Georg), Hosten, N. (Norbert), Hottenga, J.J. (Jouke Jan), Huentelman, M.J. (Matthew), Pol, H.H., Ikeda, M. (Masashi), Jack, C.R. (Clifford R.), Jenkinson, S. (Sarah), Johnson, R. (Robert), Jönsson, E.G. (Erik G.), Jukema, J.W., Kahn, R. (René), Kanai, R. (Ryota), Kloszewska, I. (Iwona), Knopman, D.S. (David S.), Kochunov, P. (Peter), Kwok, J.B. (John B.), Lawrie, S. (Stephen), Lemaître, H. (Herve), Liu, X. (Xinmin), Longo, D.L. (Dan L.), Lopez, O.L. (Oscar L.), Lovestone, S. (Simon), Martinez, O. (Oliver), Martinot, J.-L. (Jean-Luc), Mattay, V.S. (Venkata S.), McDonald, C. (Colm), McIntosh, A.M. (Andrew), McMahon, F.J. (Francis J.), McMahon, K.L. (Katie L.), Mecocci, P. (Patrizia), Melle, I. (Ingrid), Meyer-Lindenberg, A. (Andreas), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant W.), Morris, D.W. (Derek W), Mosley, T.H. (Thomas H.), Mühleisen, T.W. (Thomas), Müller-Myhsok, B. (B.), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nichols, T.E. (Thomas), Niessen, W.J. (Wiro), Nöthen, M.M. (Markus), Nyberg, L. (Lars), Ohi, K. (Kazutaka), Olvera, R.L. (Rene), Ophoff, R.A. (Roel), Pandolfo, M. (Massimo), Paus, T. (Tomas), Pausova, Z. (Zdenka), Penninx, B.W.J.H. (Brenda), Pike, G.B. (G. Bruce), Potkin, S.G. (Steven), Psaty, B.M. (Bruce), Reppermund, S., Rietschel, M. (Marcella), Roffman, J.L. (Joshua), Seiferth, N. (Nina), Rotter, J.I. (Jerome I.), Ryten, M. (Mina), Sacco, R.L. (Ralph L.), Sachdev, P.S. (Perminder), Saykin, A.J. (Andrew), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, C.J. (Christopher), Sigursson, S. (Sigurdur), Simmons, A. (Andrew), Singleton, A. (Andrew), Sisodiya, S.M. (Sanjay), Smith, C. (Colin), Smoller, J.W., Soininen, H. (H.), Steen, V.M. (Vidar), Stott, D.J. (David J.), Sussmann, J. (Jessika), Thalamuthu, A. (Anbupalam), Toga, A.W. (Arthur W.), Traynor, B. (Bryan), Troncoso, J.C. (Juan), Tsolaki, M. (Magda), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Hernández, M.C.V. (Maria C. Valdés), Brug, M.P. (Marcel) van der, Lugt, A. (Aad) van der, Wee, N.J. (Nic) van der, Haren, N.E.M. (Neeltje E.) van, Ent, D. (Dennis) van 't, Tol, M.J.D. (Marie-José) van, Vardarajan, B.N. (Badri), Vellas, B. (Bruno), Veltman, D.J. (Dick), Völzke, H. (Henry), Walter, H.J. (Henrik), Wardlaw, J. (Joanna), Wassink, A.M.J. (Annemarie), Weale, M.E. (Michael), Weinberger, D.R. (Daniel R.), Weiner, M.W. (Michael W.), Wen, W. (Wei), Westman, E. (Eric), White, T.J.H. (Tonya), Wong, T.Y. (Tien Y.), Wright, C.B. (Clinton B.), Zielke, R.H. (Ronald H.), Zonderman, A.B., Martin, N.G. (Nicholas), Duijn, C.M. (Cornelia) van, Wright, M.J. (Margaret), Longstreth Jr, W.T., Schumann, G. (Gunter), Grabe, H.J. (Hans Jörgen), Franke, B. (Barbara), Launer, L.J. (Lenore), Medland, S.E. (Sarah), Seshadri, S. (Sudha), Thompson, P.M. (Paul), Ikram, M.K. (Kamran), Hibar, D.P. (Derrek), Adams, H.H.H. (Hieab), Jahanshad, N. (Neda), Chauhan, G. (Ganesh), Stein, J.L., Hofer, E. (Edith), Rentería, M.E. (Miguel), Bis, J.C. (Joshua), Arias-Vásquez, A. (Alejandro), Ikram, M.K. (M. Kamran), Desrivières, S. (Sylvane), Vernooij, M.W. (Meike), Abramovic, L. (Lucija), Alhusaini, S. (Saud), Amin, N. (Najaf), Andersson, M. (Micael), Arfanakis, K. (Konstantinos), Aribisala, B. (Benjamin), Armstrong, N.J. (Nicola J.), Athanasiu, L. (Lavinia), Axelsson, T. (Tomas), Beecham, A.H. (Ashley), Beiser, A. (Alexa), Bernard, M. (Manon), Blanton, S.H. (Susan H.), Bohlken, M.M. (Marc M.), Boks, M.P.M. (Marco), Bralten, L.B.C. (Linda), Brickman, A.M. (Adam M.), Carmichael, O. (Owen), Chakravarty, M.M. (M. Mallar), Chen, Q. (Qiang), Ching, C.R.K. (Christopher), Chouraki, V. (Vincent), Cuellar-Partida, G. (Gabriel), Crivello, F. (Fabrice), Braber, A. (Anouk) den, Doan, N.T. (Nhat Trung), Ehrlich, S.M. (Stefan), Giddaluru, S. (Sudheer), Goldman, A.L. (Aaron L.), Gottesman, R.F. (Rebecca), Grimm, O. (Oliver), Griswold, M.D. (Michael), Guadalupe, T. (Tulio), Gutman, B.A. (Boris A.), Hass, J. (Johanna), Haukvik, U.K. (Unn), Hoehn, D. (David), Holmes, A.J. (Avram), Hoogman, M. (Martine), Janowitz, D. (Deborah), Jia, T. (Tianye), Jørgensen, K.N. (Kjetil N.), Karbalai, N. (Nazanin), Kasperaviciute, D. (Dalia), Kim, S. (Shinseog), Klein, M. (Marieke), Kraemer, B. (Bernd), Lee, P.H. (Phil), Liewald, D.C.M. (David), Lopez, L.M. (Lorna), Luciano, M. (Michelle), MacAre, C. (Christine), Marquand, A.F. (Andre F.), Matarin, M. (Mar), Mather, R., Mattheisen, M. (Manuel), McKay, D.R. (David R.), Milaneschi, Y. (Yuri), Muñoz Maniega, S. (Susana), Nho, K. (Kwangsik), Nugent, A.C. (Allison), Nyquist, P. (Paul), Loohuis, L.M.O. (Loes M. Olde), Oosterlaan, J. (Jaap), Papmeyer, M. (Martina), Pirpamer, L. (Lukas), Pütz, B. (Benno), Ramasamy, A. (Adaikalavan), Richards, J.S. (Jennifer S.), Risacher, S.L. (Shannon), Roiz-Santiañez, R. (Roberto), Rommelse, N. (Nanda), Ropele, S. (Stefan), Rose, E.J. (Emma), Royle, N.A. (Natalie), Rundek, T. (Tatjana), Sämann, P.G. (Philipp), Saremi, A. (Arvin), Satizabal, C.L. (Claudia), Schmaal, L. (Lianne), Schork, N.J. (Nicholas), Shen, L. (Li), Shin, J. (Jean), Shumskaya, E. (Elena), Smith, A.V. (Albert Vernon), Sprooten, R. (Roy), Strike, L.T. (Lachlan), Teumer, A. (Alexander), Tordesillas-Gutierrez, D. (Diana), Toro, R. (Roberto), Trabzuni, D. (Danyah), Trompet, S. (Stella), Vaidya, D. (Dhananjay), van der Grond, J. (Jeroen), Lee, S.J. (Sven) van der, Van Der Meer, D. (Dennis), Van Donkelaar, M.M.J. (Marjolein M. J.), Eijk, K.R. (Kristel) van, Erp, T.G.M. (Theo G.) van, Van Rooij, D. (Daan), Walton, E. (Esther), Westlye, L.T. (Lars), Whelan, C.D. (Christopher), Windham, B.G. (Gwen), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Woldehawariat, G. (Girma), Björnsson, A. (Asgeir), Wolfers, T. (Thomas), Yanek, L.R. (Lisa), Yang, J. (Jingyun), Zijdenbos, A.P., Zwiers, M.P. (Marcel), Agartz, I. (Ingrid), Almasy, L. (Laura), Ames, D.J. (David), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Arepalli, S. (Sampath), Assareh, A.A., Barral, S. (Sandra), Bastin, M.E. (Mark), Becker, D.M. (Diane M.), Becker, J.T. (James), Bennett, D.A. (David A.), Blangero, J. (John), Bokhoven, H. (Hans) van, Boomsma, D.I. (Dorret), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Brunner, H.G., Buckner, M., Buitelaar, J.K. (Jan), Bulayeva, K. (Kazima), Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D.M. (Dara), Cavalleri, G. (Gianpiero), Cheng, C.-Y. (Ching-Yu), Cichon, S. (Sven), Cookson, M.R. (Mark), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Curran, J.E. (Joanne), Czisch, M. (Michael), Dale, A.M. (Anders), Davies, G.E. (Gareth), Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Jager, P.L. (Philip) de, Zubicaray, G.I. (Greig) de, Deary, I.J. (Ian), Debette, S. (Stéphanie), DeCarli, C. (Charles), Delanty, N., Depondt, C. (Chantal), DeStefano, A.L. (Anita), Dillman, A. (Allissa), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drevets, D.A. (Douglas), Duggirala, R. (Ravi), Dyer, M.D. (Matthew), Enzinger, C. (Christian), Erk, S., Espeseth, T. (Thomas), Fedko, I.O. (Iryna O.), Fernández, G. (Guillén), Ferrucci, L. (Luigi), Fisher, S.E. (Simon), Fleischman, D. (Debra), Ford, I. (Ian), Fornage, M. (Myriam), Foroud, T. (Tatiana), Fox, P.T. (Peter), Francks, C. (Clyde), Fukunaga, M. (Masaki), Gibbs, J.R. (J. Raphael), Glahn, D.C. (David), Gollub, R.L. (Randy), Göring, H.H.H. (Harald H.), Green, R.C. (Robert C.), Gruber, O. (Oliver), Gudnason, V. (Vilmundur), Guelfi, S. (Sebastian), Håberg, A.K. (Asta K.), Hansell, N.K. (Narelle), Hardy, J. (John), Hartman, C.A. (C.), Hashimoto, R. (Ryota), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Le Hellard, S. (Stephanie), Hernandez, D.G. (Dena), Heslenfeld, D.J. (Dirk), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Holsboer, F. (Florian), Homuth, G. (Georg), Hosten, N. (Norbert), Hottenga, J.J. (Jouke Jan), Huentelman, M.J. (Matthew), Pol, H.H., Ikeda, M. (Masashi), Jack, C.R. (Clifford R.), Jenkinson, S. (Sarah), Johnson, R. (Robert), Jönsson, E.G. (Erik G.), Jukema, J.W., Kahn, R. (René), Kanai, R. (Ryota), Kloszewska, I. (Iwona), Knopman, D.S. (David S.), Kochunov, P. (Peter), Kwok, J.B. (John B.), Lawrie, S. (Stephen), Lemaître, H. (Herve), Liu, X. (Xinmin), Longo, D.L. (Dan L.), Lopez, O.L. (Oscar L.), Lovestone, S. (Simon), Martinez, O. (Oliver), Martinot, J.-L. (Jean-Luc), Mattay, V.S. (Venkata S.), McDonald, C. (Colm), McIntosh, A.M. (Andrew), McMahon, F.J. (Francis J.), McMahon, K.L. (Katie L.), Mecocci, P. (Patrizia), Melle, I. (Ingrid), Meyer-Lindenberg, A. (Andreas), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant W.), Morris, D.W. (Derek W), Mosley, T.H. (Thomas H.), Mühleisen, T.W. (Thomas), Müller-Myhsok, B. (B.), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nichols, T.E. (Thomas), Niessen, W.J. (Wiro), Nöthen, M.M. (Markus), Nyberg, L. (Lars), Ohi, K. (Kazutaka), Olvera, R.L. (Rene), Ophoff, R.A. (Roel), Pandolfo, M. (Massimo), Paus, T. (Tomas), Pausova, Z. (Zdenka), Penninx, B.W.J.H. (Brenda), Pike, G.B. (G. Bruce), Potkin, S.G. (Steven), Psaty, B.M. (Bruce), Reppermund, S., Rietschel, M. (Marcella), Roffman, J.L. (Joshua), Seiferth, N. (Nina), Rotter, J.I. (Jerome I.), Ryten, M. (Mina), Sacco, R.L. (Ralph L.), Sachdev, P.S. (Perminder), Saykin, A.J. (Andrew), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, C.J. (Christopher), Sigursson, S. (Sigurdur), Simmons, A. (Andrew), Singleton, A. (Andrew), Sisodiya, S.M. (Sanjay), Smith, C. (Colin), Smoller, J.W., Soininen, H. (H.), Steen, V.M. (Vidar), Stott, D.J. (David J.), Sussmann, J. (Jessika), Thalamuthu, A. (Anbupalam), Toga, A.W. (Arthur W.), Traynor, B. (Bryan), Troncoso, J.C. (Juan), Tsolaki, M. (Magda), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Hernández, M.C.V. (Maria C. Valdés), Brug, M.P. (Marcel) van der, Lugt, A. (Aad) van der, Wee, N.J. (Nic) van der, Haren, N.E.M. (Neeltje E.) van, Ent, D. (Dennis) van 't, Tol, M.J.D. (Marie-José) van, Vardarajan, B.N. (Badri), Vellas, B. (Bruno), Veltman, D.J. (Dick), Völzke, H. (Henry), Walter, H.J. (Henrik), Wardlaw, J. (Joanna), Wassink, A.M.J. (Annemarie), Weale, M.E. (Michael), Weinberger, D.R. (Daniel R.), Weiner, M.W. (Michael W.), Wen, W. (Wei), Westman, E. (Eric), White, T.J.H. (Tonya), Wong, T.Y. (Tien Y.), Wright, C.B. (Clinton B.), Zielke, R.H. (Ronald H.), Zonderman, A.B., Martin, N.G. (Nicholas), Duijn, C.M. (Cornelia) van, Wright, M.J. (Margaret), Longstreth Jr, W.T., Schumann, G. (Gunter), Grabe, H.J. (Hans Jörgen), Franke, B. (Barbara), Launer, L.J. (Lenore), Medland, S.E. (Sarah), Seshadri, S. (Sudha), Thompson, P.M. (Paul), and Ikram, M.K. (Kamran)
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017
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18. Novel genetic loci associated with hippocampal volume

Author: Hibar, D.P., Adams, H.H.H., Jahanshad, N., Chauhan, G., Stein, J.L., Hofer, E., Renteria, M.E., Bis, J.C., Arias-Vasquez, A., Ikram, M.K., Desrivières, S., Vernooij, M.W., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beecham, A.H., Beiser, A., Bernard, M., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chen, Q., Ching, C.R.K., Chouraki, V., Cuellar-Partida, G., Crivello, F., den Braber, A., Doan, N.T., Ehrlich, S., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Grimm, O., Griswold, M.E., Guadalupe, T., Gutman, B.A., Hass, J., Haukvik, U.K., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Jørgensen, K.N., Karbalai, N., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A.F., Matarin, M., Mather, K.A., Mattheisen, M., McKay, D.R., Milaneschi, Y., Munoz Maniega, S., Nho, K., Nugent, A.C., Nyquist, P., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pirpamer, L., Putz, B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Ropele, S., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Saremi, A., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Trompet, S., Vaidya, D., Van der Grond, J., van der Lee, S.J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Wittfeld, K., Woldehawariat, G., Wolf, C., Wolfers, T., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., de Craen, A.J.M., de Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Deary, I.J., Debette, S., DeCarli, C., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Enzinger, C., Erk, S., Espeseth, T., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Fornage, M., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Håberg, A.K., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Huentelman, M., Pol, H.E.H., Ikeda, M., Jack Jr, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schmidt, H., Schofield, P.R., Sigursson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Tsolaki, M., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., van der Lugt, A., van der Wee, N.J.A., van Haren, N.E.M., van ’t Ent, D., van Tol, M-J, Vardarajan, B.N., Vellas, B., Veltman, D.J., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, R.H., Zonderman, A.B., Martin, N.G., van Duijn, C.M., Wright, M.J., Longstreth, W.T., Schumann, G., Grabe, H.J., Franke, B., Launer, L.J., Medland, S.E., Seshadri, S., Thompson, P.M., Ikram, M.A., Hibar, D.P., Adams, H.H.H., Jahanshad, N., Chauhan, G., Stein, J.L., Hofer, E., Renteria, M.E., Bis, J.C., Arias-Vasquez, A., Ikram, M.K., Desrivières, S., Vernooij, M.W., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beecham, A.H., Beiser, A., Bernard, M., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chen, Q., Ching, C.R.K., Chouraki, V., Cuellar-Partida, G., Crivello, F., den Braber, A., Doan, N.T., Ehrlich, S., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Grimm, O., Griswold, M.E., Guadalupe, T., Gutman, B.A., Hass, J., Haukvik, U.K., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Jørgensen, K.N., Karbalai, N., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A.F., Matarin, M., Mather, K.A., Mattheisen, M., McKay, D.R., Milaneschi, Y., Munoz Maniega, S., Nho, K., Nugent, A.C., Nyquist, P., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pirpamer, L., Putz, B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Ropele, S., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Saremi, A., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Trompet, S., Vaidya, D., Van der Grond, J., van der Lee, S.J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Wittfeld, K., Woldehawariat, G., Wolf, C., Wolfers, T., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., de Craen, A.J.M., de Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Deary, I.J., Debette, S., DeCarli, C., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Enzinger, C., Erk, S., Espeseth, T., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Fornage, M., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Håberg, A.K., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Huentelman, M., Pol, H.E.H., Ikeda, M., Jack Jr, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schmidt, H., Schofield, P.R., Sigursson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Tsolaki, M., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., van der Lugt, A., van der Wee, N.J.A., van Haren, N.E.M., van ’t Ent, D., van Tol, M-J, Vardarajan, B.N., Vellas, B., Veltman, D.J., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, R.H., Zonderman, A.B., Martin, N.G., van Duijn, C.M., Wright, M.J., Longstreth, W.T., Schumann, G., Grabe, H.J., Franke, B., Launer, L.J., Medland, S.E., Seshadri, S., Thompson, P.M., and Ikram, M.A.
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Published: 2017

19. Novel genetic loci underlying human intracranial volume identified through genome-wide association

Author: Adams, H.H.H., Hibar, D.P., Chouraki, V., Stein, J.L., Nyquist, P.A., Renteria, M.E., Trompet, S., Arias-Vasquez, A., Seshadri, S., Desrivières, S., Beecham, A.H., Jahanshad, N., Wittfeld, K., van der Lee, S.J., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beiser, A., Bernard, M., Bis, J.C., Blanken, L.M.E., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chauhan, G., Chen, Q., Ching, C.R.K., Cuellar-Partida, G., Braber, A.D., Doan, N.T., Ehrlich, S., Filippi, I., Ge, T., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Greven, C.U., Grimm, O., Griswold, M.E., Guadalupe, T., Hass, J., Haukvik, U.K., Hilal, S., Hofer, E., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liao, J., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A., Matarin, M., Mather, K.A., Mattheisen, M., Mazoyer, B., McKay, D.R., McWhirter, R., Milaneschi, Y., Mirza-Schreiber, N., Muetzel, R.L., Maniega, S.M., Nho, K., Nugent, A.C., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pappa, I., Pirpamer, L., Pudas, S., Pütz, B., Rajan, K.B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Thomson, R., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Vaidya, D., Van der Grond, J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Woldehawariat, G., Wolf, C., Wolfers, T., Xu, B., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Aggarwal, N.T., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Chen, C., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., De Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Erk, S., Espeseth, T., Evans, D.A., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Grabe, H.J., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Pol, H.E.H., Ikeda, M., Ikram, M.K., Jack, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Longstreth, W.T., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, K.L., McMahon, F.J., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schofield, P.R., Sigurdsson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Srikanth, V., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Tiemeier, H., Toga, A.W., Traynor, B.J., Troncoso, J., Turner, J.A., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., Van der Lugt, A., van der Wee, N.J.A., van Duijn, C.M., van Haren, N.E.M., Van′t Ent, D., van Tol, M-J, Vardarajan, B.N., Veltman, D.J., Vernooij, M.W., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, H.R., Zonderman, A.B., Deary, I.J., DeCarli, C., Schmidt, H., Martin, N.G., de Craen, A.J.M., Wright, M.J., Launer, L.J., Schumann, G., Fornage, M., Franke, B., Debette, S., Medland, S.E., Ikram, M.A., Thompson, P.M., Adams, H.H.H., Hibar, D.P., Chouraki, V., Stein, J.L., Nyquist, P.A., Renteria, M.E., Trompet, S., Arias-Vasquez, A., Seshadri, S., Desrivières, S., Beecham, A.H., Jahanshad, N., Wittfeld, K., van der Lee, S.J., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beiser, A., Bernard, M., Bis, J.C., Blanken, L.M.E., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chauhan, G., Chen, Q., Ching, C.R.K., Cuellar-Partida, G., Braber, A.D., Doan, N.T., Ehrlich, S., Filippi, I., Ge, T., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Greven, C.U., Grimm, O., Griswold, M.E., Guadalupe, T., Hass, J., Haukvik, U.K., Hilal, S., Hofer, E., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liao, J., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A., Matarin, M., Mather, K.A., Mattheisen, M., Mazoyer, B., McKay, D.R., McWhirter, R., Milaneschi, Y., Mirza-Schreiber, N., Muetzel, R.L., Maniega, S.M., Nho, K., Nugent, A.C., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pappa, I., Pirpamer, L., Pudas, S., Pütz, B., Rajan, K.B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Thomson, R., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Vaidya, D., Van der Grond, J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Woldehawariat, G., Wolf, C., Wolfers, T., Xu, B., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Aggarwal, N.T., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Chen, C., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., De Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Erk, S., Espeseth, T., Evans, D.A., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Grabe, H.J., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Pol, H.E.H., Ikeda, M., Ikram, M.K., Jack, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Longstreth, W.T., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, K.L., McMahon, F.J., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schofield, P.R., Sigurdsson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Srikanth, V., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Tiemeier, H., Toga, A.W., Traynor, B.J., Troncoso, J., Turner, J.A., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., Van der Lugt, A., van der Wee, N.J.A., van Duijn, C.M., van Haren, N.E.M., Van′t Ent, D., van Tol, M-J, Vardarajan, B.N., Veltman, D.J., Vernooij, M.W., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, H.R., Zonderman, A.B., Deary, I.J., DeCarli, C., Schmidt, H., Martin, N.G., de Craen, A.J.M., Wright, M.J., Launer, L.J., Schumann, G., Fornage, M., Franke, B., Debette, S., Medland, S.E., Ikram, M.A., and Thompson, P.M.
Abstract: Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
Published: 2016

20. Mediterranean diet and carotid atherosclerosis in the Northern Manhattan study

Author: Gardener, H. Wright, C.B. Cabral, D. Scarmeas, N. Gu, Y. Cheung, K. Elkind, M.S.V. Sacco, R.L. Rundek, T.
Abstract: Objective: Adherence to a Mediterranean-style diet (MeDi) may protect against clinical vascular events by reducing atherosclerosis, but data is limited. This is the first observational study of the association between MeDi adherence and carotid plaque thickness and area. Methods: The study included 1374 participants of the population-based Northern Manhattan Study with diet assessed and carotid intima-media thickness (cIMT) and plaque measured using B-mode ultrasound (mean age 66±9years, 60% female, 60% Hispanic, 18% White, 19% Black). A MeDi adherence score (range=0-9, 9 representing maximal adherence) was examined continuously and in quintiles (3/4/5/6-9 vs. 0-2). Results: Mean cIMT=0.9±0.1mm and 57% had plaque (median plaque thickness=1.5mm, 75th percentile=2.2; median plaque area=4.2mm2, 75th percentile=15.8). There was no association between MeDi and cIMT or plaque presence. MeDi adherence was inversely associated with the 75th percentile of plaque thickness and median of plaque area in quantile regression analyses. These associations persisted after controlling for demographics, smoking, physical activity, and total energy consumption (effect of a 1-point increase in MeDi score on the 75th percentile of plaque thickness=-0.049mm, p=0.03; median of plaque area=-0.371mm2, p=0.03), and when additionally controlling for vascular disease biomarkers, medication use, BMI, and previous cardiac disease. The protective associations appeared strongest for those with a MeDi score of 5 (4th quintile) vs. 0-2 (bottom quintile). Differential effects of a MeDi on plaque thickness and area across race/ethnic groups was suggested. Conclusions: Moderate and strict adherence to a MeDi may protect against a higher burden of carotid atherosclerotic plaque, which may mediate the protection against clinical vascular events. Efforts to improve adherence to a MeDi are critical to reducing the burden of atherosclerotic disease. © 2014.
Published: 2014

21. Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: A pooled analysis of 97 prospective cohorts with 1·8 million participants

Author: Lu, Y. Hajifathalian, K. Ezzati, M. Woodward, M. Rimm, E.B. Danaei, G. Selmer, R. Strand, B.H. Dobson, A. Hozawa, A. Nozaki, A. Okayama, A. Rodgers, A. Tamakoshi, A. Zhou, B.F. Zhou, B. Yao, C.H. Jiang, C.Q. Gu, D.F. Heng, D. Giles, G.G. Shan, G.L. Whitlock, G. Arima, H. Kim, H.C. Christensen, H. Horibe, H. Maegawa, H. Tanaka, H. Ueshima, H. Zhang, H.Y. Kim, I.S. Suh, I. Fuh, J.L. Lee, J. Woo, J. Xie, J.X. Zhou, J. Hughes, K. Jamrozik, K. Nakachi, K. Sakata, K. Shimamoto, K. Chen, L.Q. Liu, L.S. Hobbs, M. Iida, M. Kagaya, M. Divitini, M.L. Luszcz, M. Nakamura, M. Huang, M.S. Knuiman, M.W. Aoki, N. Norman, P. Sritara, P. Yang, Q.D. Broadhurst, R. Huxley, R. Jackson, R. Norton, R. Ameratunga, S. Ho, S.C. Li, S.C. Jee, S.H. Chew, S.K. Macmahon, S. Choudhury, S.R. Saitoh, S. Yao, S.X. Welborn, T.A. Lam, T.H. Hashimoto, T. Ohkubo, T. Pan, W.-H. Duan, X.F. Fang, X. Wu, X.G. Fang, X.H. Yu, X.H. Li, Y.H. He, Y. Imai, Y. Kita, Y. Kiyohara, Y. Matsutani, Y. Hong, Z. Wu, Z.L. Chen, Z.M. Wu, Z.S. Tang, Z. Li, Z.Z. Parker, E.D. Pereira, M.A. Stevens, J. Panagiotakos, D.B. Pitsavos, C. Attia, J.R. Dâ€™este, C.A. Zhang, X. Clays, E. De Bacquer, D.A.O. Van Herck, K. Morrison, H.I. Wang, F. Chuang, S.-Y. Yeh, W.-T. Chen, Z. Smith, M.C. Zhou, M. Wang, W. Zhang, X.-T. Zhao, D. Vollset, S.E. Fuchs, S.C. Fuchs, F.D. Moreira, L.B. Dontas, I.A. Dontas, C.A. Kafatos, A.G. Moschandreas, J. Lanti, M. Menotti, A. Kromhout, D. Jensen, M.K. Overvad, K. Tjonneland, A. Klotsche, J. Wittchen, H.-U. Fischer, S. Hanefeld, M. Schwanebeck, U. Simons, L.A. Simons, J. Bender, R. Matthies, S. Nissinen, A. Tolonen, H.K. Tuomilehto, J. Chaturvedi, N. Fuller, J.H. Soedamah-Muthu, S.S. Kotseva, K. Wood, D.A. Bots, M.L. Moons, K.G.M. Heliovaara, M. Knekt, P.B. Rissanen, H. Ferrie, J.E. Shipley, M.J. Smith, G.D. Johansson, S. Lappas, G. Rosengren, A. Sham, A. Yu, R.H.Y. Hata, J. Ninomiya, T. Hoshide, S. Kario, K. Rastenyte, D. Tamosiunas, A. de Simone, G. Devereux, R.B. Gerdts, E. Colquhoun, D.M. Keech, A.C. Kirby, A.C. Mizuno, K. Nakamura, H. Uchiyama, S. Bassett, J.K. Hodge, A.M. Wilhelmsen, L. Dhaliwal, S.S. Nakamura, Y. Kadota, A. Okamura, T. Sandvei, M.S. Vatten, L.J. Vik, A. Morkedal, B. Romundstad, P.R. Elkind, M.S.V. Gardener, H. Sacco, R.L. Mignano, A. Novo, S. Rizzo, M. Assmann, G. Schulte, H. Lissner, L. Skoog, I. Sundh, V. Marin, A. Medrano, M.J. Hofman, A. Kuningas, M. Stricker, B.H. van der Graaf, Y. Visseren, F.L.J. Lee, J.J.M. Bemelmans, W. de Groot, L.C.P.G.M. de Hollander, E.L. Adachi, H. Hirai, Y. Azizi, F. Hadaegh, F. Khalili, D. Mathiesen, E.B. Njolstad, I. Wilsgaard, T. Can, G. Onat, A. Arnlov, J. Sundstrom, J. Blackburn, H.W. Jacobs, D.R. Averna, M.R. Cefalu, A.B. Noto, D. Concin, H. Nagel, G. Ulmer, H. Krasnow, R.E. Swan, G.E. Kivimaki, M. David Batty, G. Milic, N. Ostojic, M.C. Parapid, B. Geleijnse, J.M. Waterham, E. Feskens, E.J. The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects)
Abstract: Background Body-mass index (BMI) and diabetes have increased worldwide, whereas global average blood pressure and cholesterol have decreased or remained unchanged in the past three decades. We quantified how much of the effects of BMI on coronary heart disease and stroke are mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors. Methods We pooled data from 97 prospective cohort studies that collectively enrolled 1·8 million participants between 1948 and 2005, and that included 57 161 coronary heart disease and 31 093 stroke events. For each cohort we excluded participants who were younger than 18 years, had a BMI of lower than 20 kg/m2, or who had a history of coronary heart disease or stroke. We estimated the hazard ratio (HR) of BMI on coronary heart disease and stroke with and without adjustment for all possible combinations of blood pressure, cholesterol, and glucose. We pooled HRs with a random-effects model and calculated the attenuation of excess risk after adjustment for mediators. Findings The HR for each 5 kg/m2 higher BMI was 1·27 (95% CI 1·23-1·31) for coronary heart disease and 1·18 (1·14-1·22) for stroke after adjustment for confounders. Additional adjustment for the three metabolic risk factors reduced the HRs to 1·15 (1·12-1·18) for coronary heart disease and 1·04 (1·01-1·08) for stroke, suggesting that 46% (95% CI 42-50) of the excess risk of BMI for coronary heart disease and 76% (65-91) for stroke is mediated by these factors. Blood pressure was the most important mediator, accounting for 31% (28-35) of the excess risk for coronary heart disease and 65% (56-75) for stroke. The percentage excess risks mediated by these three mediators did not differ significantly between Asian and western cohorts (North America, western Europe, Australia, and New Zealand). Both overweight (BMI ≥25 to
Published: 2014

22. The association between a mediterranean-style diet and kidney function in the northern manhattan study cohort

Author: Khatri, M. Moon, Y.P. Scarmeas, N. Gu, Y. Gardener, H. Cheung, K. Wright, C.B. Sacco, R.L. Nickolas, T.L. Elkind, M.S.V.
Abstract: Background and objectives Various dietary strategies have been investigated to slow kidney function decline. However, it is unknownwhether aMediterranean diet,which has been associatedwith improved cardiovascular risk, is associated with change in kidney function Design, setting, participants, & measurements This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinine measurements were taken a mean 6.9 years apart. A baseline dietary questionnairewas extrapolated into a previously used 9-point scoring system(MeDi). The primary outcomewas incident eGFR,60 ml/min per 1.73 m2using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline (≥2.5 ml/min per 1.73 m2 per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors. Results Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m2. Incident eGFR,60 ml/min per 1.73 m2 developed in 14%. In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR,60 ml/min per 1.73 m2 (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98). Conclusions A Mediterranean diet was associated with a reduced incidence of eGFR,60 ml/min per 1.73m2 and upper quartile of eGFR decline in a multiethnic cohort. © 2014 by the American Society of Nephrology.
Published: 2014

23. Update on the global burden of ischemic and hemorrhagic stroke in 1990-2013: The GBD 2013 study.

Author: Hamadeh R.R., Harewood H., Springer K., Da Costa Leite I., Lindsay M.P., Riccio P.M., Li B., Jiang G., Ma J., Zhou M., Zhu S., Liang X., Zhang Y., Alcala-Cerra G., Temesgen A., Sahle B.W., Prabhakaran D., Gupta R., Rajagopalan V., Warouw T.S., O'Donnell M.J., Ricci S., Asad M.M., Bwire V.K., Jee S.H., Khang Y.-H., Myint C.Y., Norheim O., Khalifa S.E., De Dieu Ngirabega J., Nyemazi J.P., Muhimpundu M.A., Saeedi M., Bedi N., Havmoeller R., Atwine L., O'Callaghan F., Critchley J.A., Ezzati M., Rothwell P.M., Whiteley W., Chen Z., Colomar M., Durrani A.M., Dayama A., Amlie-Lefond C., Huang C., Sumeet C., Cundiff D.K., Qato D., Kabagambe E.K., Ding E., Bukhman G., Kwan G., Thurston G., Coresh J., Lefondulq K., Corriere M.A., Mainoo N., Schwartz S.M., Fung T., Byers T.E., Rocca W.A., Lo W., Feigin V.L., Krishnamurthi R.V., Parmar P., Norrving B., Mensah G.A., Bennett D.A., Barker-Collo S., Moran A.E., Sacco R.L., Truelsen T., Davis S., Pandian J.D., Naghavi M., Forouzanfar M.H., Nguyen G., Johnson C.O., Vos T., Meretoja A., Murray C.J.L., Roth G.A., Abd-Allah F., Abera S.F., Akinyemi R.O., Salman R.A.-S., Anderson C.S., Bahit M.C., Banerjee A., Basu S., Beauchamp N.J., Bornstein N.M., Brainin M., Cabral N.L., Campos-Nonato I., Caso V., Catala-Lopez F., Chowdhury R., Christensen H.K., Connor M.D., DeVeber G., Dharmaratne S.D., Dokova K., Donnan G., Endres M., Fernandes J.G., Gankpe F., Geleijnse J.M., Gillium R.F., Giroud M., Hankey G.J., Jeemon P., Jonas J.B., Kazi D.S., Kengne A.P., Kim D., Kissela B.M., Kokubo Y., Kosen S., Kravchenko M., Lavados P.M., Liu M., Lotufo P.A., MacKay M.T., Malekzadeh R., Mehndiratta M.M., Melaku Y.A., Misganaw A., Nand D., Piradov M., Pourmalek F., Rojas-Rueda D., Roy N., Sahathevan R., Sampson U.K.A., Shamalov N., Sheth K.N., Shinohara Y., Shiue I., Soljak M., Sposato L.A., Stroumpoulis K., Tanne D., Thrift A.G., Tirschwell D.L., Varakin Y., Venketasubramanian N., Vlassov V.V., Wang W., Westerman R., Wolfe C., Yu C., Yunjin K., Stavreski B., Pearse E., Ademi Z., Guliyev T., Hamadeh R.R., Harewood H., Springer K., Da Costa Leite I., Lindsay M.P., Riccio P.M., Li B., Jiang G., Ma J., Zhou M., Zhu S., Liang X., Zhang Y., Alcala-Cerra G., Temesgen A., Sahle B.W., Prabhakaran D., Gupta R., Rajagopalan V., Warouw T.S., O'Donnell M.J., Ricci S., Asad M.M., Bwire V.K., Jee S.H., Khang Y.-H., Myint C.Y., Norheim O., Khalifa S.E., De Dieu Ngirabega J., Nyemazi J.P., Muhimpundu M.A., Saeedi M., Bedi N., Havmoeller R., Atwine L., O'Callaghan F., Critchley J.A., Ezzati M., Rothwell P.M., Whiteley W., Chen Z., Colomar M., Durrani A.M., Dayama A., Amlie-Lefond C., Huang C., Sumeet C., Cundiff D.K., Qato D., Kabagambe E.K., Ding E., Bukhman G., Kwan G., Thurston G., Coresh J., Lefondulq K., Corriere M.A., Mainoo N., Schwartz S.M., Fung T., Byers T.E., Rocca W.A., Lo W., Feigin V.L., Krishnamurthi R.V., Parmar P., Norrving B., Mensah G.A., Bennett D.A., Barker-Collo S., Moran A.E., Sacco R.L., Truelsen T., Davis S., Pandian J.D., Naghavi M., Forouzanfar M.H., Nguyen G., Johnson C.O., Vos T., Meretoja A., Murray C.J.L., Roth G.A., Abd-Allah F., Abera S.F., Akinyemi R.O., Salman R.A.-S., Anderson C.S., Bahit M.C., Banerjee A., Basu S., Beauchamp N.J., Bornstein N.M., Brainin M., Cabral N.L., Campos-Nonato I., Caso V., Catala-Lopez F., Chowdhury R., Christensen H.K., Connor M.D., DeVeber G., Dharmaratne S.D., Dokova K., Donnan G., Endres M., Fernandes J.G., Gankpe F., Geleijnse J.M., Gillium R.F., Giroud M., Hankey G.J., Jeemon P., Jonas J.B., Kazi D.S., Kengne A.P., Kim D., Kissela B.M., Kokubo Y., Kosen S., Kravchenko M., Lavados P.M., Liu M., Lotufo P.A., MacKay M.T., Malekzadeh R., Mehndiratta M.M., Melaku Y.A., Misganaw A., Nand D., Piradov M., Pourmalek F., Rojas-Rueda D., Roy N., Sahathevan R., Sampson U.K.A., Shamalov N., Sheth K.N., Shinohara Y., Shiue I., Soljak M., Sposato L.A., Stroumpoulis K., Tanne D., Thrift A.G., Tirschwell D.L., Varakin Y., Venketasubramanian N., Vlassov V.V., Wang W., Westerman R., Wolfe C., Yu C., Yunjin K., Stavreski B., Pearse E., Ademi Z., and Guliyev T.
Abstract: Background: Global stroke epidemiology is changing rapidly. Although age-standardized rates of stroke mortality have decreased worldwide in the past 2 decades, the absolute numbers of people who have a stroke every year, and live with the consequences of stroke or die from their stroke, are increasing. Regular updates on the current level of stroke burden are important for advancing our knowledge on stroke epidemiology and facilitate organization and planning of evidence-based stroke care. Objective(s): This study aims to estimate incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke (IS) and hemorrhagic stroke (HS) for 188 countries from 1990 to 2013. Methodology: Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated using all available data on mortality and stroke incidence, prevalence and excess mortality. Statistical models and country-level covariate data were employed, and all rates were age-standardized to a global population. All estimates were produced with 95% uncertainty intervals (UIs). Result(s): In 2013, there were globally almost 25.7 million stroke survivors (71% with IS), 6.5 million deaths from stroke (51% died from IS), 113 million DALYs due to stroke (58% due to IS) and 10.3 million new strokes (67% IS). Over the 1990-2013 period, there was a significant increase in the absolute number of DALYs due to IS, and of deaths from IS and HS, survivors and incident events for both IS and HS. The preponderance of the burden of stroke continued to reside in developing countries, comprising 75.2% of deaths from stroke and 81.0% of stroke-related DALYs. Globally, the proportional contribution of stroke-related DALYs and deaths due to stroke compared to all diseases increased from 1990 (3.54% (95% UI 3.11-4.00) and 9.66% (95% UI 8.47-10.70), respectively) to 2013 (4.62% (95% UI 4.01-5.30) and 11.75% (95% UI 10.45-13.31), respectively), but there was
Published: 2015

24. Carotid Intima-Media thickness progression and risk of vascular events in people with Diabetes: Results from the PROG-IMT collaboration

Author: Lorenz, M.W. (Matthias), Price, J.F. (Jackie F.), Robertson, C.M. (Christine M), Bots, M.L. (Michiel), Polak, J.F. (Joseph F.), Poppert, H. (Holger), Kavousi, M. (Maryam), Dörr, M. (Marcus), Stensland, E. (Eva), Ducimetiere, P. (Pierre), Ronkainen, K. (Kimmo), Kiechl, S. (Stefan), Sitzer, M. (Matthias), Rundek, T. (Tatjana), Lind, L. (Lars), Liu, J. (Jing), Bergstrom, G. (Goran), Grigore, L. (Liliana), Bokemark, L. (Lena), Friera, A. (Alfonsa), Yanez, D. (David), Bickel, H. (Horst), Ikram, M.A. (Arfan), Volzke, H. (Henry), Johnsen, S.H., Empana, J.P. (Jean Philippe), Tuomainen, T.-P. (Tomi-Pekka), Willeit, J. (Johann), Steinmetz, H. (Helmuth), Desvarieux, M. (Moise), Xie, W. (Wuxiang), Schmidt, C. (Caroline), Norata, G.D. (Giuseppe), Suárez, C. (Carmen), Sander, D. (Dirk), Hofman, A. (Albert), Schminke, U. (Ulf), Mathiesen, E.B. (Ellisiv), Plichart, M. (Matthieu), Kauhanen, J. (Jussi), Sacco, R.L. (Ralph), McLachlan, S. (Stela), Zhao, D. (Dong), Fagerberg, B. (Bjorn), Catapano, A.L. (Alberico L.), Gabriel, R. (Rafael), Franco, O.H. (Oscar), Bulbul, A. (Alpaslan), Scheckenbach, F. (Frank), Pflug, A. (Anja), Gao, L. (Lu), Thompson, S.G. (Simon G.), Lorenz, M.W. (Matthias), Price, J.F. (Jackie F.), Robertson, C.M. (Christine M), Bots, M.L. (Michiel), Polak, J.F. (Joseph F.), Poppert, H. (Holger), Kavousi, M. (Maryam), Dörr, M. (Marcus), Stensland, E. (Eva), Ducimetiere, P. (Pierre), Ronkainen, K. (Kimmo), Kiechl, S. (Stefan), Sitzer, M. (Matthias), Rundek, T. (Tatjana), Lind, L. (Lars), Liu, J. (Jing), Bergstrom, G. (Goran), Grigore, L. (Liliana), Bokemark, L. (Lena), Friera, A. (Alfonsa), Yanez, D. (David), Bickel, H. (Horst), Ikram, M.A. (Arfan), Volzke, H. (Henry), Johnsen, S.H., Empana, J.P. (Jean Philippe), Tuomainen, T.-P. (Tomi-Pekka), Willeit, J. (Johann), Steinmetz, H. (Helmuth), Desvarieux, M. (Moise), Xie, W. (Wuxiang), Schmidt, C. (Caroline), Norata, G.D. (Giuseppe), Suárez, C. (Carmen), Sander, D. (Dirk), Hofman, A. (Albert), Schminke, U. (Ulf), Mathiesen, E.B. (Ellisiv), Plichart, M. (Matthieu), Kauhanen, J. (Jussi), Sacco, R.L. (Ralph), McLachlan, S. (Stela), Zhao, D. (Dong), Fagerberg, B. (Bjorn), Catapano, A.L. (Alberico L.), Gabriel, R. (Rafael), Franco, O.H. (Oscar), Bulbul, A. (Alpaslan), Scheckenbach, F. (Frank), Pflug, A. (Anja), Gao, L. (Lu), and Thompson, S.G. (Simon G.)
Abstract: OBJECTIVE Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes. RESEARCH DESIGN AND MET
Published: 2015
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25. Sex differences in stroke incidence, prevalence,mortality and disability-adjusted life years: Results from the global burden of disease study 2013.

Author: Patrice Lindsay M., Thrift A.G., Stroumpoulis K., Prabhakaran D., Gupta R., Rajagopalan V., Kosen S., Warouw T.S., O'Donnell M.J., Shinohara Y., Asad M.M., Bwire V.K., Jee S.H., Khang Y.-H., Sahathevan R., Campos-Nonato I., Gankpe F., Myint C.Y., Norheim O., Khalifa S.E., Kravchenko M., Piradov M., Shalamov N., Varakin Y., De Dieu Ngirabega J., Nyemazi J.P., Muhimpundu M.A., Saeedi M., Bedi N., Havmoeller R., Atwine L., O'Callaghan F., Critchley J.A., Ezzati M., Soljak M., Connor M.D., Rothwell P.M., Salman R.A.-S., Whiteley W., Chen Z., Durrani A.M., Dayama A., Moran A.E., Misganaw A., Amlie-Lefond C., Huang C., Sumeet C., Cundiff D.K., Kazi D.S., Qato D., Kabagambe E.K., Ding E., Bukhman G., Kwan G., Coresh J., Lefondulq K., Corriere M.A., Mainoo N., Beauchamp N.J., Schwartz S.M., Chugh S., Fung T., Byers T.E., Sampson U.K.A., Rocca W.A., Lo W., Barker-Collo S., Bennett D.A., Krishnamurthi R.V., Parmar P., Feigin V.L., Naghavi M., Forouzanfar M.H., Johnson C.O., Nguyen G., Mensah G.A., Vos T., Murray C.J.L., Roth G.A., Abd-Allah F., Abera S.F., Akinyemi R.O., Bahit M.C., Banerjee A., Basu S., Brainin M., Bornstein N.M., Caso V., Catala-Lopez F., Chowdhury R., Christensen H.K., Colomar M., Davis S., Deveber G., Dharmaratne S.D., Donnan G., Dorairaj P., Dokova K., Endres M., Fernandes J.G., Geleijnse J.M., Gillum R.F., Giroud M., Hamadeh R.R., Hankey G.J., Jeemon P., Jiang G., Jonas J.B., Kalkonde Y., Kengne A.P., Kim D., Kissela B.M., Kokubo Y., Lavados P.M., Lotufo P.A., Mackay M.T., Malekzadeh R., Mehndiratta M.M., Nand D., Norrving B., Pandian J.D., Perkins H., Pourmalek F., Ricci S., Riccio P.M., Rojas-Rueda D., Roy N., Sacco R.L., Sheth K.N., Shiue I., Sposato L.A., Tanne D., Thurston G.D., Tirschwell D.L., Venketasubramanian N., Vlassov V.V., Westerman R., Wolfe C., Yunjin K., Meretoja A., Stavreski B., Anderson C.S., Pearse E., Ademi Z., Guliyev T., Harewood H., Springer K., Da Costa Leite I., Cabral N.L., Li B., Yu C., Ma J., Zhou M., Liu M., Zhu S., Wang W., Liang X., Zhang Y., Alcala-Cerra G., Truelsen T., Temesgen A., Sahle B.W., Melaku Y.A., Patrice Lindsay M., Thrift A.G., Stroumpoulis K., Prabhakaran D., Gupta R., Rajagopalan V., Kosen S., Warouw T.S., O'Donnell M.J., Shinohara Y., Asad M.M., Bwire V.K., Jee S.H., Khang Y.-H., Sahathevan R., Campos-Nonato I., Gankpe F., Myint C.Y., Norheim O., Khalifa S.E., Kravchenko M., Piradov M., Shalamov N., Varakin Y., De Dieu Ngirabega J., Nyemazi J.P., Muhimpundu M.A., Saeedi M., Bedi N., Havmoeller R., Atwine L., O'Callaghan F., Critchley J.A., Ezzati M., Soljak M., Connor M.D., Rothwell P.M., Salman R.A.-S., Whiteley W., Chen Z., Durrani A.M., Dayama A., Moran A.E., Misganaw A., Amlie-Lefond C., Huang C., Sumeet C., Cundiff D.K., Kazi D.S., Qato D., Kabagambe E.K., Ding E., Bukhman G., Kwan G., Coresh J., Lefondulq K., Corriere M.A., Mainoo N., Beauchamp N.J., Schwartz S.M., Chugh S., Fung T., Byers T.E., Sampson U.K.A., Rocca W.A., Lo W., Barker-Collo S., Bennett D.A., Krishnamurthi R.V., Parmar P., Feigin V.L., Naghavi M., Forouzanfar M.H., Johnson C.O., Nguyen G., Mensah G.A., Vos T., Murray C.J.L., Roth G.A., Abd-Allah F., Abera S.F., Akinyemi R.O., Bahit M.C., Banerjee A., Basu S., Brainin M., Bornstein N.M., Caso V., Catala-Lopez F., Chowdhury R., Christensen H.K., Colomar M., Davis S., Deveber G., Dharmaratne S.D., Donnan G., Dorairaj P., Dokova K., Endres M., Fernandes J.G., Geleijnse J.M., Gillum R.F., Giroud M., Hamadeh R.R., Hankey G.J., Jeemon P., Jiang G., Jonas J.B., Kalkonde Y., Kengne A.P., Kim D., Kissela B.M., Kokubo Y., Lavados P.M., Lotufo P.A., Mackay M.T., Malekzadeh R., Mehndiratta M.M., Nand D., Norrving B., Pandian J.D., Perkins H., Pourmalek F., Ricci S., Riccio P.M., Rojas-Rueda D., Roy N., Sacco R.L., Sheth K.N., Shiue I., Sposato L.A., Tanne D., Thurston G.D., Tirschwell D.L., Venketasubramanian N., Vlassov V.V., Westerman R., Wolfe C., Yunjin K., Meretoja A., Stavreski B., Anderson C.S., Pearse E., Ademi Z., Guliyev T., Harewood H., Springer K., Da Costa Leite I., Cabral N.L., Li B., Yu C., Ma J., Zhou M., Liu M., Zhu S., Wang W., Liang X., Zhang Y., Alcala-Cerra G., Truelsen T., Temesgen A., Sahle B.W., and Melaku Y.A.
Abstract: Background: Accurate information on stroke burden in men and women are important for evidence-based healthcare planning and resource allocation. Previously, limited research suggested that the absolute number of deaths from stroke in women was greater than in men, but the incidence and mortality rates were greater in men. However, sex differences in various metrics of stroke burden on a global scale have not been a subject of comprehensive and comparable assessment for most regions of the world, nor have sex differences in stroke burden been examined for trends over time. Method(s): Stroke incidence, prevalence, mortality, disability-adjusted life years (DALYs) and healthy years lost due to disability were estimated as part of the Global Burden of Disease (GBD) 2013 Study. Data inputs included all available information on stroke incidence, prevalence and death and case fatality rates. Analysis was performed separately by sex and 5-year age categories for 188 countries. Statistical models were employed to produce globally comprehensive results over time. All rates were age-standardized to a global population and 95% uncertainty intervals (UIs) were computed. Finding(s): In 2013, global ischemic stroke (IS) and hemorrhagic stroke (HS) incidence (per 100,000) in men (IS 132.77 (95% UI 125.34-142.77); HS 64.89 (95% UI 59.82-68.85)) exceeded those of women (IS 98.85 (95% UI 92.11-106.62); HS 45.48 (95% UI 42.43-48.53)). IS incidence rates were lower in 2013 compared with 1990 rates for both sexes (1990 male IS incidence 147.40 (95% UI 137.87-157.66); 1990 female IS incidence 113.31 (95% UI 103.52-123.40)), but the only significant change in IS incidence was among women.Copyright © 2015 S. Karger AG, Basel.
Published: 2015

26. Update on the Global Burden of Ischemic and Hemorrhagic Stroke in 1990-2013: The GBD 2013 Study

Author: Feigin, V.L., Krishnamurthi, R.V., Parmar, P., Norrving, B., Mensah, G.A., Bennett, D., Barker-Collo, S., Moran, A.E., Sacco, R.L., Truelsen, T., Davis, S.C., Pandian, J.D., Naghavi, M.R., Forouzanfar, M.H., Nguyen, G., Johnson, C., Vos, T., Meretoja, A., Murray, C.J., Roth, G.A., Geleijnse, J.M., Feigin, V.L., Krishnamurthi, R.V., Parmar, P., Norrving, B., Mensah, G.A., Bennett, D., Barker-Collo, S., Moran, A.E., Sacco, R.L., Truelsen, T., Davis, S.C., Pandian, J.D., Naghavi, M.R., Forouzanfar, M.H., Nguyen, G., Johnson, C., Vos, T., Meretoja, A., Murray, C.J., Roth, G.A., and Geleijnse, J.M.
Abstract: Background: Global stroke epidemiology is changing rapidly. Although age-standardized rates of stroke mortality have decreased worldwide in the past 2 decades, the absolute numbers of people who have a stroke every year, and live with the consequences of stroke or die from their stroke, are increasing. Regular updates on the current level of stroke burden are important for advancing our knowledge on stroke epidemiology and facilitate organization and planning of evidence-based stroke care. Objectives: This study aims to estimate incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke (IS) and hemorrhagic stroke (HS) for 188 countries from 1990 to 2013. Methodology: Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated using all available data on mortality and stroke incidence, prevalence and excess mortality. Statistical models and country-level covariate data were employed, and all rates were age-standardized to a global population. All estimates were produced with 95% uncertainty intervals (UIs). Results: In 2013, there were globally almost 25.7 million stroke survivors (71% with IS), 6.5 million deaths from stroke (51% died from IS), 113 million DALYs due to stroke (58% due to IS) and 10.3 million new strokes (67% IS). Over the 1990-2013 period, there was a significant increase in the absolute number of DALYs due to IS, and of deaths from IS and HS, survivors and incident events for both IS and HS. The preponderance of the burden of stroke continued to reside in developing countries, comprising 75.2% of deaths from stroke and 81.0% of stroke-related DALYs. Globally, the proportional contribution of stroke-related DALYs and deaths due to stroke compared to all diseases increased from 1990 (3.54% (95% UI 3.11-4.00) and 9.66% (95% UI 8.47-10.70), respectively) to 2013 (4.62% (95% UI 4.01-5.30) and 11.75% (95% UI 10.45-13.31), respectively), but there was a d
Published: 2015

27. Quality of life declines after first ischemic stroke: The Northern Manhattan Study(e–Pub ahead of print)(CME)

Author: Dhamoon, M.S., Moon, Y.P., Paik, M.C., Boden-Albala, B., Rundek, T., Sacco, R.L., and Elkind, M.S.V.
Subjects: Adult, Aged, 80 and over, Male, Psychiatric Status Rating Scales, Insurance, Health, Urban Population, Medicaid, Incidence, Articles, Recovery of Function, Disease-Free Survival, United States, Brain Ischemia, Stroke, Recurrence, Risk Factors, Quality of Life, Humans, Female, New York City, Prospective Studies, Aged, Follow-Up Studies
Abstract: Quality of life (QOL) after stroke is poorly characterized. We sought to determine long-term natural history and predictors of QOL among first ischemic stroke survivors without stroke recurrence or myocardial infarction (MI).In the population-based, multiethnic Northern Manhattan Study, QOL was prospectively assessed at 6 months and annually for 5 years using the Spitzer QOL index (QLI), a 10-point scale. Functional status was assessed using the Barthel Index (BI) at regular intervals, and cognition using the Mini-Mental State Examination at 1 year. Generalized estimating equations estimated the association between patient characteristics and repeated QOL measures over 5 years. Follow-up was censored at death, recurrent stroke, or MI.There were 525 incident ischemic stroke patients/=40 years (mean age 68.6 +/- 12.4 years). QLI declined after stroke (annual change -0.10, 95% confidence interval -0.17 to -0.04), after adjusting for age, sex, race-ethnicity, education, insurance, depressed mood, stroke severity, bladder continence, and stroke laterality. This decline remained when BI/=95 was added to the model as a time-dependent covariate, and functional status also predicted QLI. Changes in QLI over time differed by insurance status (p for interaction = 0.0017), with a decline for those with Medicaid/no insurance (p0.0001) but not Medicare/private insurance (p = 0.98).In this population-based study, QOL declined annually up to 5 years after stroke among survivors free of recurrence or MI and independently of other risk factors. QLI declined more among Medicaid patients and was associated with age, mood, stroke severity, urinary incontinence, functional status, cognition, and stroke laterality.
Published: 2010

28. Stroke outcome in clinical trial patients deriving from different countries

Author: Ali, M., Atula, S., Bath, P.M.W., Grotta, J., Hacke, W., Lyden, P., Marler, J.R., Sacco, R.L., and Lees, K.R.
Abstract: Background and Purpose: Stroke incidence and outcome vary widely within and across geographical locations. We examined whether differences in index stroke severity, stroke risk factors, mortality, and stroke outcome across geographical locations remain after adjusting for case mix.\ud \ud Methods: We analyzed 3284 patients from the Virtual International Stroke Trials Archive (VISTA). We used logistic regression to examine the incidence of mild index stroke, functional, and neurological outcomes after accounting for age, medical history, year of trial recruitment, and initial stroke severity in the functional and neurological outcome analyses. We examined mortality between geographical regions using a Cox proportional hazards model, accounting for age, initial stroke severity, medical history, and year of trial recruitment.\ud \ud Results Patients enrolled in the USA and Canada had the most severe index strokes. Those recruited in Austria and Switzerland had the best functional and neurological outcomes at 90 days (P\ud \ud Conclusion: We identified regional variations in index stroke severity, outcome, and mortality for patients enrolled in ischemic stroke clinical trials over the past 13 years that were not fully explained by case mix. Index stroke severity was greater in patients enrolled after 1998, with no significant improvement in outcomes compared to those enrolled before 1998.
Published: 2009

29. The Virtual International Stroke Trials Archive

Author: Ali, M., Bath, P.M.W., Curram, J., Davis, S.M., Diener, H.-C., Donnan, G.A., Fisher, M., Gregson, B.A., Grotta, J., Hacke, W., Hennerici, M.G., Hommel, M., Kaste, M., Marler, J.R., Sacco, R.L., Teal, P., Wahlgren, N.-G., Warach, S., Weir, C.J., and Lees, K.R.
Published: 2007

30. Gavestinel does not improve outcome after acute intracerebral hemorrhage: an analysis from the GAIN International and GAIN Americas studies

Author: Haley, E.C., Thompson, J.L.P., Levin, B., Davis, S., Lees, K.R., Pittman, J.G., Derosa, J.T., Ordronneau, P., Brown, D.L., and Sacco, R.L.
Abstract: Background and Purpose: Glycine Antagonist in Neuroprotection (GAIN) International and GAIN Americas trials were prospectively designed, randomized, placebo-controlled trials of gavestinel, a glycine-site antagonist and putative neuroprotectant drug administered within 6 hours of suspected ischemic or hemorrhagic stroke. Both trials reported that gavestinel was ineffective in ischemic stroke. This analysis reports the results in those with primary intracerebral hemorrhage.\ud \ud Methods: The primary hypothesis was that gavestinel treatment did not alter outcome, measured at 3 months by the Barthel Index (BI), from acute intracerebral hemorrhage, based on pooled results from both trials. The BI scores were divided into 3 groups: 95 to 100 (independent), 60 to 90 (assisted independence), and 0 to 55 (dependent) or dead.\ud \ud Results: In total, 3450 patients were randomized in GAIN International (N=1804) and GAIN Americas (N=1646). Of these, 571 were ultimately identified to have spontaneous intracerebral hematoma on baseline head computerized tomography scan. The difference in distribution of trichotomized BI scores at 3 months between gavestinel and placebo was not statistically significant (P=0.09). Serious adverse events were reported at similar rates in the 2 treatment groups.\ud \ud Conclusions: These observations from the combined GAIN International and GAIN Americas trials suggest that gavestinel is not of substantial benefit or harm to patients with primary intracerebral hemorrhage. These findings are similar to results previously reported in patients with ischemic stroke.
Published: 2005

31. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study

Author: O'Donnell, M.J., Serpault, Damien Xavier, Xiufeng, Liu, Zhang, H.Y., Chin, S.L., Rao-Melacini, P., Rangarajan, S., Islam, Sarmin, Pais, P., McQueen, M.J., Mondo, C., Damasceno, A., Lopez-Jaramillo, P., Hankey, G.J., Dans, A.L., Yusoff, K., Truelsen, T., Diener, H.C., Sacco, R.L., Ryglewicz, D., Czlonkowska, A., Hansen, Camilla Weimar Buhr, Wang, Yu, Shah, Sayed Yusuf, O'Donnell, M.J., Serpault, Damien Xavier, Xiufeng, Liu, Zhang, H.Y., Chin, S.L., Rao-Melacini, P., Rangarajan, S., Islam, Sarmin, Pais, P., McQueen, M.J., Mondo, C., Damasceno, A., Lopez-Jaramillo, P., Hankey, G.J., Dans, A.L., Yusoff, K., Truelsen, T., Diener, H.C., Sacco, R.L., Ryglewicz, D., Czlonkowska, A., Hansen, Camilla Weimar Buhr, Wang, Yu, and Shah, Sayed Yusuf
Abstract: Background The contribution of various risk factors to the burden of stroke worldwide is unknown, particularly in countries of low and middle income. We aimed to establish the association of known and emerging risk factors with stroke and its primary subtypes, assess the contribution of these risk factors to the burden of stroke, and explore the differences between risk factors for stroke and myocardial infarction. Methods We undertook a standardised case-control study in 22 countries worldwide between March 1, 2007, and April 23, 2010. Cases were patients with acute first stroke (within 5 days of symptoms onset and 72 h of hospital admission). Controls had no history of stroke, and were matched with cases for age and sex. All participants completed a structured questionnaire and a physical examination, and most provided blood and urine samples. We calculated odds ratios (ORs) and population-attributable risks (PARs) for the association of all stroke, ischaemic stroke, and intracerebral haemorrhagic stroke with selected risk factors. Findings In the first 3000 cases (n=2337, 78%, with ischaemic stroke; n=663, 22%, with intracerebral haemorrhagic stroke) and 3000 controls, significant risk factors for all stroke were: history of hypertension (OR 2.64, 99% CI 2.26-3.08; PAR 34.6%, 99% CI 30.4-39.1); current smoking (2.09, 1.75-2.51; 18.9%, 15.3-23.1); waist-to-hip ratio (1.65, 1.36-1.99 for highest vs lowest tertile; 26.5%, 18.8-36.0); diet risk score (1.35, 1.11-1.64 for highest vs lowest tertile; 18.8%, 11.2-29.7); regular physical activity (0.69, 0.53-0.90; 285%, 14 5-48.5); diabetes mellitus (1.36, 1.10-1.68; 5.0%, 2.6-9.5); alcohol intake (1.51, 1.18-1.92 for more than 30 drinks per month or binge drinking; 3 - 8%, 0.9-14.4); psychosocial stress (1.30, 1.06-1.60; 46%, 2.1-9.6) and depression (1.35, 1.10-1.66; 5.2%, 2.7-9.8); cardiac causes (2.38, 1.77-3.20; 6.7%, 4.8-9.1); and ratio of apolipoproteins B to A1 (1.89, 1.49-2.40 for highest vs lowest tertile; 24.9%
Published: 2010

32. Perivascular Spaces Are Associated with Atherosclerosis: An Insight from the Northern Manhattan Study

Author: Gutierrez, J., primary, Rundek, T., additional, Ekind, M.S.V., additional, Sacco, R.L., additional, and Wright, C.B., additional
Published: 2013
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33. Visual hemineglect and hemihallucinations in a patient with a subcortical infarction

Author: Chamorro, A., Sacco, R.L., Ciecierski, K., Binder, J.R., Tatemichi, T.K., and Mohr, J.P.
Subjects: Attention -- Abnormalities, Stroke (Disease) -- Complications, Brain -- Infarction, Hallucinations and illusions -- Case studies, Health, Psychology and mental health
Abstract: Hemineglect can be a consequence of a right hemisphere stroke. The patient fails to notice features of the left side of the visual field; in some cases the patient fails to recognize the left side of his/her own body. However, in the recent case of a 41-year-old alcoholic woman, the patient failed to have hallucinations in the left visual space. She initially experienced left-sided weakness, which suggested a right-hemisphere stroke. Testing revealed a mild neglect of the left space, although the patient could recognize and name objects and people in the left space when asked. The patient's medical history was remarkable for a number of hospitalizations for alcohol intoxication. On the day after admission, the patient began to develop hallucinations of birds and people, which were presumed to be a result of alcohol withdrawal. She claimed that the hallucinations were only present on the right side. The hallucinations persisted for three days, and the hemineglect lasted for about three weeks. Four weeks after her admission, hemiplegia was the only persisting symptom. Magnetic resonance imaging revealed the presence of an infarction in the putamen and the posterior limb of the internal capsule. The infarction extended into the anteromedial part of the temporal lobe and the corona radiata. This anatomical distribution of the infarction is significant, since hemineglect syndromes generally involve the parietal lobe of the brain, which was apparently spared in this case. The lack of involvement of the parietal lobe may account for the mildness of the hemineglect, in which the patient could identify objects in the left extrapersonal space. The authors suggest that the infarction may have disrupted connections between the basal ganglia and the parietal lobe, so that the signals which resulted in hallucinatory perceptions in the right visual space by the left hemisphere could not cause similar left-side hallucinatory perceptions in the damaged right hemisphere. (Consumer Summary produced by Reliance Medical Information, Inc.)
Published: 1990

34. Oral Anticoagulation in Patients with Cardiomyopathy or Heart Failure in Sinus Rhythm

Author: Pullicino, P., primary, Thompson, J.L.P., additional, Mohr, J.P., additional, Sacco, R.L., additional, Freudenberger, R., additional, Levin, B., additional, and Homma, S., additional
Published: 2008
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35. National Stroke Association guidelines for the management of transient ischemic attacks

Author: Johnston, S.C., primary, Nguyen-Huynh, M.N., additional, Schwarz, M.E., additional, Fuller, K., additional, Williams, C.E., additional, Josephson, S.A., additional, Hankey, G.J., additional, Hart, R.G., additional, Levine, S.R., additional, Biller, J., additional, Brown, R.D., additional, Sacco, R.L., additional, Kappelle, L.J., additional, Koudstaal, P.J., additional, Bogousslavsky, J., additional, Caplan, L.R., additional, van Gijn, J., additional, Algra, A., additional, Rothwell, P.M., additional, Adams, H.P., additional, and Albers, G.W., additional
Published: 2007
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36. Impact of Valvular Thickness on Stroke Recurrence in Medically Treated Patients with Stroke

Author: Okajima, K., primary, Abe, Y., additional, Suzuki, K., additional, Salameh, M.J., additional, Di Tullio, M.R., additional, Jin, Z., additional, Sacco, R.L., additional, Mohr, J.P., additional, and Homma, S., additional
Published: 2007
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37. American Heart Association; American Stroke Association Stroke Council. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: co-sponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group

Author: Goldstein, L.B., primary, Adams, R., additional, Alberts, M.J., additional, Appel, L.J., additional, Brass, L.M., additional, Bushnell, C.D., additional, Culebras, A., additional, DeGraba, T.J., additional, Gorelick, P.B., additional, Guyton, J.R., additional, Hart, R.G., additional, Howard, G., additional, Kelly-Hayes, M., additional, Nixon, J.V., additional, and Sacco, R.L., additional
Published: 2006
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38. American Heart Association/American Stroke Association Council on Stroke; Council on Cardiovascular Radiology and Intervention; American Academy of Neurology. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline

Author: Sacco, R.L., primary, Adams, R., additional, Albers, G., additional, Alberts, M.J., additional, Benavente, O., additional, Furie, K., additional, Goldstein, L.B., additional, Gorelick, P., additional, Halperin, J., additional, Harbaugh, R., additional, Johnston, S.C., additional, Katzan, I., additional, Kelly-Hayes, M., additional, Kenton, E.J., additional, Marks, M., additional, Schwamm, L.H., additional, and Tomsick, T., additional
Published: 2006
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39. The incidence of deep and lobar intracerebral hemorrhage in whites, blacks, and Hispanics

Author: Flaherty, M. L., primary, Woo, D., additional, Broderick, J., additional, Labovitz, D.L., additional, Halim, A., additional, Boden-Albala, B., additional, Hauser, W.A., additional, and Sacco, R.L., additional
Published: 2006
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40. Subarachnoid Hemorrhage Incidence among Whites, Blacks and Caribbean Hispanics: The Northern Manhattan Study

Author: Labovitz, D.L., primary, Halim, A.X., additional, Brent, B., additional, Boden-Albala, B., additional, Hauser, W.A., additional, and Sacco, R.L., additional
Published: 2006
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41. Effect of medical treatment in stroke patients with patent foramen ovale. patent foramen ovale in cryptogenic stroke study

Author: Homma, S., primary, Sacco, R.L., additional, Tullio, M.R., additional, Sciacca, R.R., additional, and Mohr, J.P., additional
Published: 2002
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42. La warfarina no es más eficaz que la aspirina en la prevención de los accidentes cerebrovasculares isquémicos recurrentes

Author: Mohr, J.P., primary, Thompson, J.L.P., additional, Lazar, R.M., additional, Levin, B., additional, Sacco, R.L., additional, Furie, K.L., additional, and Argimon, Josep M., additional
Published: 2002
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43. Predictors of resource use after acute hospitalization

Author: Rundek, T., primary, Mast, H., additional, Hartmann, A., additional, Boden–Albala, B., additional, Lennihan, L., additional, Lin, I.-F., additional, Paik, M.C., additional, and Sacco, R.L., additional
Published: 2000
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44. The protective effect of moderate alcohol consumption on ischemic stroke

Author: Sacco, R.L., primary, Elkind, M., additional, and Boden-Albala, B., additional
Published: 1999
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45. Lipid and lipoprotein levels remain stable in acute ischemic stroke: the Northern Manhattan Stroke Study

Author: Kargman, D.E, primary, Tuck, C, additional, Berglund, L, additional, Lin, I.-F, additional, Mukherjee, R.S, additional, Thompson, E.V, additional, Jones, J, additional, Boden-Albala, B, additional, Paik, M.C, additional, and Sacco, R.L, additional
Published: 1998
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46. Increased left atrial size as a risk factor for ischemic stroke in a multiethnic population

Author: Di Tullio, M.R., primary, Sacco, R.L., additional, Sciacca, R.R., additional, Boden-Albala, B., additional, Zwas, D.R., additional, Fard, A.K., additional, Titova, I., additional, Mendoza, L.M., additional, and Homma, S., additional
Published: 1998
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47. Are More Complex Study Designs Needed for Future Acute Stroke Trials?

Author: Mohr, J.P., primary, Mast, H., additional, Thompson, J.L.P., additional, and Sacco, R.L., additional
Published: 1998
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48. EEG in lacunar strokes in not normal

Author: Lee, K.S., primary, Walczak, T.S., additional, Sacco, R.L., additional, and Cohen, J., additional
Published: 1995
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49. Parametric Modeling of Stroke Recurrence

Author: Foulkes, M.A., primary, Sacco, R.L., additional, Mohr, J.P., additional, Hier, D.B., additional, Price, T.R., additional, and Wolf, P.A., additional
Published: 1994
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50. Lower prevalence of silent brain infarcts in the physically active

Author: Willey, J.Z., Moon, Y.P., Paik, M.C., Yoshita, M., DeCarli, C., Sacco, R.L., Elkind, M.S.V., and Wright, C.B.
Abstract: To examine the independent association between physical activity and subclinical cerebrovascular disease as measured by silent brain infarcts (SBI) and white matter hyperintensity volume (WMHV).
Published: 2011
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