Sudha Seshadri, MD

Professor of Neurology

Phone: 61Sudha Seshadri7.414.1337
Fax: 617.638.8086
Email: suseshad@bu.edu
Location: Robinson, B602

 

Background

Dr. Sudha Seshadri completed her MBBS from the Christian Medical College, Madras University, and her MD in Internal Medicine and DM in Neurology from the All India Institute of Medical Sciences, New Delhi, India. Additionally, she has completed a Residency in Neurology at the Boston University School of Medicine and a Fellowship in the Neurobiology of Aging and Alzheimer Disease at the University of Massachusetts Medical Center. She has previously worked as Assistant Professor of Neurology at the All India Institute of Medical Sciences, New Delhi, and joined the Boston University School of Medicine’s Department of Neurology in May 2001 as Assistant Professor in the Department of Neurology. She also serves as Co-Director of Medical Education for the Neurology Residency and Clerkship programs.

Research Interests

I have been an investigator at the Framingham Heart Study (FHS) since 1998, leading the clinical neurology and neurogenetics cores since 2005 and currently serve as PI on 3 R01 grants. As a board certified neurologist and Professor of Neurology at the Boston University School of Medicine, I run a Geriatric Memory Disorders and Dementia clinic, supervise a resident general neurology clinic and cover the in-patient, consult and emergency services for one month in each year. I also served as Co-Director of Medical Education for the Neurology Residency Program between 2005 and 2012. I was Director of the neurology segment of the Biology of Disease/ Disease and Therapy course for 2nd year medical students between 2008-2010 and have resumed this role for 2015. I currently spend 75% of my time on research and mentoring within the context of the Framingham study and serve as primary mentor for two post-doctoral research fellows and a junior faculty K23 awardee.

In my research capacity, I currently lead the clinical neurology and neurogenetics cores at the FHS, where we explore the cumulated and age-specific impacts of a wide variety of genomic and environmental risk factors underlying stroke, dementia and brain aging across 3 generations of participants. This entails undertaking brain MRI, cognitive tests, brain autopsies, biomarker, candidate gene, genome-wide association, sequencing and expression studies. At FHS, my key contributions have included updating the dementia database with improved tracking, review and new classification systems, studying novel biomarkers such as BDNF, NGF and beta-amyloid, and establishing a brain bank program. In addition I play a major role in consolidating, refining and expanding various aspects of the MRI and stroke databases. Further, as lead neurogenetics investigator I have funded whole exome sequencing on over 1300 Framingham Study participants.

My research focuses on 4 interrelated areas: (a) exploring the correlates of subclinical brain aging including establishing norms for brain MRI and cognitive test performance and relating these measures to novel risk factors (such as visceral fat mass), multiple circulating biomarkers and clinical and subclinical indices of vascular and metabolic disease; (b) the epidemiology of stroke and vascular cognitive impairment including the lifetime risk of stroke, cognitive decline and dementia following stroke, the role of parental stroke and midlife risk factors in determining late-life stroke risk and temporal trends in stroke risk over the past 50 years; (c) the epidemiology of dementia and Alzheimer’s disease (AD) including describing the lifetime risk of AD and relating traditional and novel biomarkers (homocysteine, lipids, diabetes, estrogen, bone mineral density, thyroid function, inflammation) to the risk of dementia and AD. I have been especially interested in exploring the role of reversible lifestyle, vascular and metabolic risk factors in determining dementia risk with a special focus on understanding the putative causal pathways and biomarkers, such as leptin and other adipokines, BDNF and other neurotrophic factors, in mediating this risk, and (d) understanding the genomic and epigenetic variation underlying brain aging, stroke, AD and vascular cognitive impairment.

My most significant research contributions have been (i) developing the concept of lifetime risk as applicable to dementia and other chronic diseases, (ii) helping to establish plasma homocysteine as an important risk marker for dementia and AD (including a first author paper in the NEJM in 2002 that has had over 1400 citations), (iii) relating low plasma leptin levels to the risk of dementia and AD (published in JAMA, 2009 as senior author), (iv) describing a novel gene, NINJ2, associated with ischemic stroke (NEJM, 2009 as corresponding author), (v) describing two genes, BIN1 and EXOCL2, associated with Alzheimer disease in the largest, multi-centric genome-wide association study to date (JAMA, 2010 as first author) and identifying novel genes underlying hippocampal volume in healthy adults (Nature Genetics, 2012 as Senior author).

I am currently a PI on 3 NIH funded grants, a key co-investigator on 7 grants (PI of subcontract on 2), and have over 150 peer-reviewed publications and reviews. I also established, partially fund and coordinate the neurology phenotype working group within the international Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium started in January 2008. This consortium brings together investigators from several of the leading cohort studies, the FHS, the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health study (CHS), the Rotterdam study, the Age, Gene, Environment Susceptibility- Reykjavik (AGES-Reykjavik) study and the Austrian Study for Prevention of Stroke (ASPS). In my capacity as coordinator of neuroCHARGE, I am also a founding member of the International Genomics of Alzheimer’s Project (IGAP) that brings together 4 major European and US groups who are currently the leaders in AD genomics research, am a PI of the Alzheimer Disease Sequencing Project (ADSP) that assesses rare genetic variation underlying PD in over 11,500 persons, a member of the Steering Committee for the International Stroke Genetics Consortium (ISGC) and Vice-Chair of the METASTROKE consortium.

A particular emphasis of mine throughout my career has been and will continue to be mentoring younger colleagues at my own institution and around the world towards academic careers. Collectively, my mentees have over 40 first author papers that I mentored published in leading journals including JAMA, Archives of Internal Medicine, Archives of Neurology, Stroke and Neurology.ADC Role

Dr. Seshadri works to facilitate joint research between the ADC and the Framingham Heart Study. She also sees patients with memory loss and Alzheimer’s disease in her clinic at the Boston University Neurological Associates on Friday afternoons.

Awards/Memberships

Awards: E. Merck Gold Medal in Neurology and Allied Sciences.

Member: Alpha Omega Alpha, American Academy of Neurology, American Medical Association, Massachusetts Medical Society, World Federation of Neurology, Alzheimer’s and Related Disorders Society of India, Neurological Society of India, Indian Academy of Neurology, Scientific Council of American Stroke Association.

Recent Publications

Click here for a full list of publications.

  1. Kaess BM, Preis SR, Beiser A, Sawyer DB, Chen TC, Seshadri S, Vasan RS. Circulating vascular endothelial growth factor and the risk of cardiovascular events. Heart. 2016 Jun 27. PMID: 27354275.
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  2. Adams SL, Tilton K, Kozubek JA, Seshadri S, Delalle I. Subcellular Changes in Bridging Integrator 1 Protein Expression in the Cerebral Cortex During the Progression of Alzheimer Disease Pathology. J Neuropathol Exp Neurol. 2016 Jun 26. PMID: 27346750.
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  3. Teumer A, Qi Q, Nethander M, Aschard H, Bandinelli S, Beekman M, Berndt SI, Bidlingmaier M, Broer L. Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits. Aging Cell. 2016 Jun 21. PMID: 27329260.
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  4. Matteini AM, Tanaka T, Karasik D, Atzmon G, Chou WC, Eicher JD, Johnson AD, Arnold AM, Callisaya ML, Davies G, Evans DS, Holtfreter B, Lohman K, Lunetta KL, Mangino M, Smith AV, Smith JA, Teumer A, Yu L, Arking DE, Buchman AS, Chibinik LB, De Jager PL, Evans DA, Faul JD, Garcia ME, Gillham-Nasenya I, Gudnason V, Hofman A, Hsu YH, Ittermann T, Lahousse L, Liewald DC, Liu Y, Lopez L, Rivadeneira F, Rotter JI, Siggeirsdottir K, Starr JM, Thomson R, Tranah GJ, Uitterlinden AG, Völker U, Völzke H, Weir DR, Yaffe K, Zhao W, Zhuang WV, Zmuda JM, Bennett DA, Cummings SR, Deary IJ, Ferrucci L, Harris TB, Kardia SL, Kocher T, Kritchevsky SB, Psaty BM, Seshadri S, Spector TD, Srikanth VK, Windham BG, Zillikens MC, Newman AB, Walston JD, Kiel DP, Murabito JM. GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. Aging Cell. 2016 Jun 21. PMID: 27325353.
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  5. Chouraki V, Reitz C, Maury F, Bis JC, Bellenguez C, Yu L, Jakobsdottir J, Mukherjee S, Adams HH, Choi SH, Larson EB, Fitzpatrick A, Uitterlinden AG, de Jager PL, Hofman A, Gudnason V, Vardarajan B, Ibrahim-Verbaas C, van der Lee SJ, Lopez O, Dartigues JF, Berr C, Amouyel P, Bennett DA, van Duijn C, DeStefano AL, Launer LJ, Ikram MA, Crane PK, Lambert JC, Mayeux R, Seshadri S. Evaluation of a Genetic Risk Score to Improve Risk Prediction for Alzheimer’s Disease. J Alzheimers Dis. 2016 Jun 18. PMID: 27340842.
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  6. De Guio F, Jouvent E, Biessels GJ, Black SE, Brayne C, Chen C, Cordonnier C, De Leeuw FE, Dichgans M, Doubal F, Duering M, Dufouil C, Duzel E, Fazekas F, Hachinski V, Ikram MA, Linn J, Matthews PM, Mazoyer B, Mok V, Norrving B, O’Brien JT, Pantoni L, Ropele S, Sachdev P, Schmidt R, Seshadri S, Smith EE, Sposato LA, Stephan B, Swartz RH, Tzourio C, van Buchem M, van der Lugt A, van Oostenbrugge R, Vernooij MW, Viswanathan A, Werring D, Wollenweber F, Wardlaw JM, Chabriat H. Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease. J Cereb Blood Flow Metab. 2016 May 11. PMID: 27170700.
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  7. Kim EJ, Yin X, Fontes JD, Magnani JW, Lubitz SA, McManus DD, Seshadri S, Vasan RS, Ellinor PT, Larson MG, Benjamin EJ, Rienstra M. Atrial fibrillation without comorbidities: Prevalence, incidence and prognosis (from the Framingham Heart Study). Am Heart J. 2016 Jul; 177:138-44. PMID: 27297859.
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  8. Pase MP, Beiser A, Enserro D, Xanthakis V, Aparicio H, Satizabal CL, Himali JJ, Kase CS, Vasan RS, DeCarli C, Seshadri S. Association of Ideal Cardiovascular Health With Vascular Brain Injury and Incident Dementia. Stroke. 2016 May; 47(5):1201-6. PMID: 27073239.
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  9. Salinas J, Beiser A, Himali JJ, Rosand J, Seshadri S, Dunn EC. Factors Associated With New-Onset Depression After Stroke. J Neuropsychiatry Clin Neurosci. 2016 Apr 8; appineuropsych15110388. PMID: 27056020.
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  10. Therkelsen KE, Preis SR, Beiser A, DeCarli C, Seshadri S, Wolf P, Au R, Fox CS. Neck Circumference, Brain Imaging Measures, and Neuropsychological Testing Measures. J Stroke Cerebrovasc Dis. 2016 Jul; 25(7):1570-81. PMID: 27056441.
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  11. Jak AJ, Preis SR, Beiser AS, Seshadri S, Wolf PA, Bondi MW, Au R. Neuropsychological Criteria for Mild Cognitive Impairment and Dementia Risk in the Framingham Heart Study. J Int Neuropsychol Soc. 2016 Mar 31; 1-7. PMID: 27029348.
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  12. Romero JR, Preis SR, Beiser A, DeCarli C, D’Agostino RB, Wolf PA, Vasan RS, Polak JF, Seshadri S. Carotid Atherosclerosis and Cerebral Microbleeds: The Framingham Heart Study. J Am Heart Assoc. 2016; 5(3). PMID: 26994127.
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  13. Maillard P, Mitchell GF, Himali JJ, Beiser A, Tsao CW, Pase MP, Satizabal CL, Vasan RS, Seshadri S, DeCarli C. Effects of Arterial Stiffness on Brain Integrity in Young Adults From the Framingham Heart Study. Stroke. 2016 Apr; 47(4):1030-6. PMID: 26965846.
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  14. Malik R, Traylor M, Pulit SL, Bevan S, Hopewell JC, Holliday EG, Zhao W, Abrantes P, Amouyel P, Attia JR, Battey TW, Berger K, Boncoraglio GB, Chauhan G, Cheng YC, Chen WM, Clarke R, Cotlarciuc I, Debette S, Falcone GJ, Ferro JM, Gamble DM, Ilinca A, Kittner SJ, Kourkoulis CE, Lemmens R, Levi CR, Lichtner P, Lindgren A, Liu J, Meschia JF, Mitchell BD, Oliveira SA, Pera J, Reiner AP, Rothwell PM, Sharma P, Slowik A, Sudlow CL, Tatlisumak T, Thijs V, Vicente AM, Woo D, Seshadri S, Saleheen D, Rosand J, Markus HS, Worrall BB, Dichgans M. Low-frequency and common genetic variation in ischemic stroke: The METASTROKE collaboration. Neurology. 2016 Mar 29; 86(13):1217-26. PMID: 26935894.
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  15. Gupta A, Giambrone AE, Gialdini G, Finn C, Delgado D, Gutierrez J, Wright C, Beiser AS, Seshadri S, Pandya A, Kamel H. Silent Brain Infarction and Risk of Future Stroke: A Systematic Review and Meta-Analysis. Stroke. 2016 Mar; 47(3):719-25. PMID: 26888534.
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  16. Choi SH, Ruggiero D, Sorice R, Song C, Nutile T, Vernon Smith A, Concas MP, Traglia M, Barbieri C, Ndiaye NC, Stathopoulou MG, Lagou V, Maestrale GB, Sala C, Debette S, Kovacs P, Lind L, Lamont J, Fitzgerald P, Tönjes A, Gudnason V, Toniolo D, Pirastu M, Bellenguez C, Vasan RS, Ingelsson E, Leutenegger AL, Johnson AD, DeStefano AL, Visvikis-Siest S, Seshadri S, Ciullo M. Six Novel Loci Associated with Circulating VEGF Levels Identified by a Meta-analysis of Genome-Wide Association Studies. PLoS Genet. 2016 Feb; 12(2):e1005874. PMID: 26910538.
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  17. Satizabal CL, Beiser AS, Chouraki V, Chêne G, Dufouil C, Seshadri S. Incidence of Dementia over Three Decades in the Framingham Heart Study. N Engl J Med. 2016 Feb 11; 374(6):523-32. PMID: 26863354.
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  18. Spartano NL, Himali JJ, Beiser AS, Lewis GD, DeCarli C, Vasan RS, Seshadri S. Midlife exercise blood pressure, heart rate, and fitness relate to brain volume 2 decades later. Neurology. 2016 Apr 5; 86(14):1313-9. PMID: 26865519.
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  19. Karakis I, Pase MP, Beiser A, Booth SL, Jacques PF, Rogers G, DeCarli C, Vasan RS, Wang TJ, Himali JJ, Annweiler C, Seshadri S. Association of Serum Vitamin D with the Risk of Incident Dementia and Subclinical Indices of Brain Aging: The Framingham Heart Study. J Alzheimers Dis. 2016 Feb 6; 51(2):451-61. PMID: 26890771.
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  20. Tsao CW, Himali JJ, Beiser AS, Larson MG, DeCarli C, Vasan RS, Mitchell GF, Seshadri S. Association of arterial stiffness with progression of subclinical brain and cognitive disease. Neurology. 2016 Feb 16; 86(7):619-26. PMID: 26791155.
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  21. Pase MP, Himali JJ, Mitchell GF, Beiser A, Maillard P, Tsao C, Larson MG, DeCarli C, Vasan RS, Seshadri S. Association of Aortic Stiffness With Cognition and Brain Aging in Young and Middle-Aged Adults: The Framingham Third Generation Cohort Study. Hypertension. 2016 Mar; 67(3):513-9. PMID: 26754644.
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  22. Freudenberger P, Petrovic K, Sen A, Töglhofer AM, Fixa A, Hofer E, Perl S, Zweiker R, Seshadri S, Schmidt R, Schmidt H. Fitness and cognition in the elderly: The Austrian Stroke Prevention Study. Neurology. 2016 Feb 2; 86(5):418-24. PMID: 26740674.
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  23. Cheng YC, Stanne TM, Giese AK, Ho WK, Traylor M, Amouyel P, Holliday EG, Malik R, Xu H, Kittner SJ, Cole JW, O’Connell JR, Danesh J, Rasheed A, Zhao W, Engelter S, Grond-Ginsbach C, Kamatani Y, Lathrop M, Leys D, Thijs V, Metso TM, Tatlisumak T, Pezzini A, Parati EA, Norrving B, Bevan S, Rothwell PM, Sudlow C, Slowik A, Lindgren A, Walters MR. Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2. Stroke. 2016 Feb; 47(2):307-16. PMID: 26732560.
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  24. Williams SR, Hsu FC, Keene KL, Chen WM, Nelson S, Southerland AM, Madden EB, Coull B, Gogarten SM, Furie KL, Dzhivhuho G, Rowles JL, Mehndiratta P, Malik R, Dupuis J, Lin H, Seshadri S, Rich SS, Sale MM, Worrall BB. Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke. Neurology. 2016 Jan 26; 86(4):351-9. PMID: 26718567.
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  25. Nayor M, Enserro DM, Beiser AS, Cheng S, DeCarli C, Vasan RS, Seshadri S. Association of Exhaled Carbon Monoxide With Stroke Incidence and Subclinical Vascular Brain Injury: Framingham Heart Study. Stroke. 2016 Feb; 47(2):383-9. PMID: 26696648.
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  26. Harris SE, Malik R, Marioni R, Campbell A, Seshadri S, Worrall BB, Sudlow CL, Hayward C, Bastin ME, Starr JM, Porteous DJ, Wardlaw JM, Deary IJ. Polygenic risk of ischemic stroke is associated with cognitive ability. Neurology. 2016 Feb 16; 86(7):611-8. PMID: 26695942.
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  27. Chatterjee S, Peters SA, Woodward M, Mejia Arango S, Batty GD, Beckett N, Beiser A, Borenstein AR, Crane PK, Haan M, Hassing LB, Hayden KM, Kiyohara Y, Larson EB, Li CY, Ninomiya T, Ohara T, Peters R, Russ TC, Seshadri S, Strand BH, Walker R, Xu W, Huxley RR. Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia. Diabetes Care. 2016 Feb; 39(2):300-7. PMID: 26681727.
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  28. Lebowitz BK, Weinstein C, Beiser A, Seshadri S, Wolf PA, Auerbach S, Au R. Lifelong Reading Disorder and Mild Cognitive Impairment: Implications for Diagnosis. J Alzheimers Dis. 2015 Nov 25; 50(1):41-5. PMID: 26639959.
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  29. Xing C, Huang J, Hsu YH, DeStefano AL, Heard-Costa NL, Wolf PA, Seshadri S, Kiel DP, Cupples LA, Dupuis J. Evaluation of power of the Illumina HumanOmni5M-4v1 BeadChip to detect risk variants for human complex diseases. Eur J Hum Genet. 2016 Jul; 24(7):1029-34. PMID: 26577045.
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  30. Seshadri S, Moonis M. Dipping to clear amyloid: Cerebrovascular reactivity and neurodegeneration-cause or effect? Neurology. 2015 Dec 1; 85(22):1918-9. PMID: 26537050.
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  31. Pase MP, Beiser A, Aparicio H, DeCarli C, Vasan RS, Murabito J, Seshadri S. Interarm differences in systolic blood pressure and the risk of dementia and subclinical brain injury. Alzheimers Dement. 2016 Apr; 12(4):438-45. PMID: 26542262.
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  32. Adams HH, Hilal S, Schwingenschuh P, Wittfeld K, van der Lee SJ, DeCarli C, Vernooij MW, Katschnig-Winter P, Habes M, Chen C, Seshadri S, van Duijn CM, Ikram MK, Grabe HJ, Schmidt R, Ikram MA. A priori collaboration in population imaging: The Uniform Neuro-Imaging of Virchow-Robin Spaces Enlargement consortium. Alzheimers Dement (Amst). 2015 Dec; 1(4):513-20. PMID: 27239529.
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  33. Escott-Price V, Sims R, Bannister C, Harold D, Vronskaya M, Majounie E, Badarinarayan N. Common polygenic variation enhances risk prediction for Alzheimer’s disease. Brain. 2015 Dec; 138(Pt 12):3673-84. PMID: 26490334.
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  34. Knopman DS, Beiser A, Machulda MM, Fields J, Roberts RO, Pankratz VS, Aakre J, Cha RH, Rocca WA, Mielke MM, Boeve BF, Devine S, Ivnik RJ, Au R, Auerbach S, Wolf PA, Seshadri S, Petersen RC. Spectrum of cognition short of dementia: Framingham Heart Study and Mayo Clinic Study of Aging. Neurology. 2015 Nov 10; 85(19):1712-21. PMID: 26453643.
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  35. Hofer E, Cavalieri M, Bis JC, DeCarli C, Fornage M, Sigurdsson S, Srikanth V, Trompet S, Verhaaren BF, Wolf C, Yang Q, Adams HH, Amouyel P, Beiser A, Buckley BM, Callisaya M, Chauhan G, de Craen AJ, Dufouil C, van Duijn CM, Ford I, Freudenberger P, Gottesman RF, Gudnason V, Heiss G, Hofman A, Lumley T, Martinez O, Mazoyer B, Moran C, Niessen WJ, Phan T, Psaty BM, Satizabal CL, Sattar N, Schilling S, Shibata DK, Slagboom PE, Smith A, Stott DJ, Taylor KD, Thomson R, Töglhofer AM, Tzourio C, van Buchem M, Wang J, Westendorp RG, Gwen Windham B, Vernooij MW, Zijdenbos A, Beare R, Debette S, Ikram MA, Jukema JW, Launer LJ, Longstreth WT, Mosley TH, Seshadri S, Schmidt H, Schmidt R. White Matter Lesion Progression: Genome-Wide Search for Genetic Influences. Stroke. 2015 Nov; 46(11):3048-57. PMID: 26451028.
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