Sudha Seshadri, MD
Adjunct Professor
Boston University School of Medicine
Dept of Neurology

MD, All India Institute of Medical Science (AIIMS)
MBBS, Christian Medical College & Hospital
DM, All India Institute of Medical Science (AIIMS)




I have been an investigator at the Framingham Heart Study (FHS) since 1998, leading the clinical neurology and neurogenetics cores since 2005 and serving as PI on 9 NIH grants, 5 R01 grants, 3 U01s and a UH2. As a board certified neurologist and Professor of Neurology at the Boston University School of Medicine, I ran a Geriatric Memory Disorders and Dementia clinic, supervised a resident general neurology clinic and covered 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 in 2015-16 and continue to teach the Dementia module. I currently spend 75% of my time on research and mentoring within the context of the Framingham study and have served as primary mentor for over 30 physician and non-physician investigators funded by a wide range of grants, national (K23, AAN, AHA) and international (Fulbright, Bettencourt-Schuller, Sidney-Sax etc.).

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 have over 280 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 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 80 first author papers that I mentored published in leading journals including NEJM, Lancet, Nature Genetics, JAMA, JAMA Internal Medicine, JAMA Neurology, Annals of Neurology, Brain, Stroke and Neurology.

Investigator
Framingham Heart Study


Director
UT Health San Antonio
Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases



2013 American Academy of Neurology: Fellow
2013-2013 Boston University: Jack Spivack Excellence in Neurosciences Award
2012 American Neurological Association: Fellow


Plasma Proteome and Risk of Alzheimer Dementia and Related Endophenotypes in the Framingham Study
07/01/2019 - 03/31/2024 (Multi-PI)
PI: Sudha Seshadri, MD
NIH/National Institute on Aging
1RF1AG063507-01

MRI, Cognitive, Genetic and Biomarker Precursors of AD & Dementia in Young Adults
06/01/2016 - 01/31/2021 (Multi-PI)
PI: Sudha Seshadri, MD
NIH/National Institute on Aging
5R01AG033040-10

MRI, Cognitive, Genetic and Biomarker Precursors of AD & Dementia in Young Adults
02/15/2016 - 01/31/2020 (Multi-PI)
PI: Sudha Seshadri, MD
NIH/National Institute on Aging
5R01AG033040-07

An integrated genetic and epigenetic approach to cerebral small vessel disease
04/01/2015 - 03/31/2019 (Subcontract PI)
University of Texas Health Science Center, Houston NIH NINDS
5R01NS087541-04

The Genetics and Biomarkers of Small Vessel stroke
07/01/2017 - 12/31/2018 (Subcontract PI)
University of Maryland, Baltimore County American Heart Assoc


Collaborative GWAS of Dementia, AD and Related MRI and Cognitive Endophenotypes
06/01/2016 - 05/31/2018 (PI)
NIH/National Institute on Aging
4R01AG033193-07

Microgial, Inflammatory and Omics Markers of Cerebral Small Vessel Disease in the CHARGE Consortium
09/30/2016 - 11/30/2017 (PI)
NIH/National Institute of Neurological Disorders & Stroke
5UH2NS100605-02

Temporal Trends, Novel Imaging and Molecular Characterization of Preclinical and Clinical Alzheimer Disease in Framingham Cohorts
09/01/2016 - 11/30/2017 (PI)
NIH/National Institute on Aging
3R01AG054076-02S1

ADSP Follow-up in Multi-Ethnic Cohorts via Endophenotypes, Omics & Model Systems
09/01/2016 - 11/30/2017 (PI)
NIH/National Institute on Aging
1U01AG052409-01

Precursors of Stroke Incidence and Prognosis
03/01/2016 - 11/30/2017 (PI)
NIH/National Institute of Neurological Disorders & Stroke
5R01NS017950-34

Showing 10 of 23 results. Show All Results


Title


Yr Title Project-Sub Proj Pubs
2021 Therapeutic target discovery in ADSP data via comprehensive whole-genome analysis incorporating ethnic diversity and systems approaches 3U01AG058589-03S1 2
2020 Multidimensional Assessment of Brain Health as A Marker of Dementia Risk and Resilience 1R01AG066524-01A1
2020 Alzheimers-focused Administrative Supplement to Enhance the Imaging Genomics of the Aging Brain Project 3R01AG058464-03S1
2020 Therapeutic target discovery in ADSP data via comprehensive whole-genome analysis incorporating ethnic diversity and systems approaches 5U01AG058589-03 2
2020 Precursors of Stroke Incidence and Prognosis 5R01NS017950-37 621
2020 Precursors of Stroke Incidence and Prognosis 5R01NS017950-37 621
2020 ADSP Follow-up in Multi-Ethnic Cohorts via Endophenotypes, Omics & Model Systems 5U01AG052409-04 55
2020 Temporal Trends, Novel Imaging and Molecular Characterization of Preclinical and Clinical Alzheimer's Disease in the Framingham Cohorts 5R01AG054076-05 83
2019 Plasma Proteome and Risk of Alzheimer Dementia and Related Endophenotypes in the Framingham Study 1RF1AG063507-01
2019 Therapeutic target discovery in ADSP data via comprehensive whole-genome analysis incorporating ethnic diversity and systems approaches 5U01AG058589-02 2
Showing 10 of 63 results. Show All Results

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

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  1. Malik R, Georgakis MK, Neitzel J, Rannikmäe K, Ewers M, Seshadri S, Sudlow CLM, Dichgans M. Midlife vascular risk factors and risk of incident dementia: Longitudinal cohort and Mendelian randomization analyses in the UK Biobank. Alzheimers Dement. 2021 Mar 22. PMID: 33749976
     
  2. Oelsner EC, Allen NB, Ali T, Anugu P, Andrews H, Asaro A, Balte PP, Barr RG, Bertoni AG, Bon J, Boyle R, Chang AA, Chen G, Cole SA, Coresh J, Cornell E, Correa A, Couper D, Cushman M, Demmer RT, Elkind MSV, Folsom AR, Fretts AM, Gabriel KP, Gallo L, Gutierrez J, Han MK, Henderson JM, Howard VJ, Isasi CR, Jacobs DR, Judd SE, Mukaz DK, Kanaya AM, Kandula NR, Kaplan R, Krishnaswamy A, Kinney GL, Kucharska-Newton A, Lee JS, Lewis CE, Levine DA, Levitan EB, Levy B, Make B, Malloy K, Manly JJ, Meyer KA, Min YI, Moll M, Moore WC, Mauger D, Ortega VE, Palta P, Parker MM, Phipatanakul W, Post W, Psaty BM, Regan EA, Ring K, Roger VL, Rotter JI, Rundek T, Sacco RL, Schembri M, Schwartz DA, Seshadri S, Shikany JM, Sims M, Hinckley Stukovsky KD, Talavera GA, Tracy RP, Umans JG, Vasan RS, Watson K, Wenzel SE, Winters K, Woodruff PG, Xanthakis V, Zhang Y, Zhang Y. Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design. medRxiv. 2021 Mar 20.View Related Profiles. PMID: 33758891
     
  3. Walker ME, O'Donnell AA, Himali JJ, Rajendran I, Melo van Lent D, Ataklte F, Jacques PF, Beiser AS, Seshadri S, Vasan RS, Xanthakis V. Associations of the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay diet with cardiac remodelling in the community: the Framingham Heart Study. Br J Nutr. 2021 Feb 23; 1-9.View Related Profiles. PMID: 33618785; DOI: 10.1017/S0007114521000660;
     
  4. Baril AA, Beiser AS, Redline S, McGrath ER, Aparicio HJ, Gottlieb DJ, Seshadri S, Pase MP, Himali JJ. Systemic inflammation as a moderator between sleep and incident dementia. Sleep. 2021 Feb 12; 44(2).View Related Profiles. PMID: 32860698
     
  5. Taliun D, Harris DN, Kessler MD, Carlson J, Szpiech ZA, Torres R, Taliun SAG, Corvelo A, Gogarten SM, Kang HM, Pitsillides AN, LeFaive J, Lee SB, Tian X, Browning BL, Das S, Emde AK, Clarke WE, Loesch DP, Shetty AC, Blackwell TW, Smith AV, Wong Q, Liu X, Conomos MP, Bobo DM, Aguet F, Albert C, Alonso A, Ardlie KG, Arking DE, Aslibekyan S, Auer PL, Barnard J, Barr RG, Barwick L, Becker LC, Beer RL, Benjamin EJ, Bielak LF, Blangero J, Boehnke M, Bowden DW, Brody JA, Burchard EG, Cade BE, Casella JF, Chalazan B, Chasman DI, Chen YI, Cho MH, Choi SH, Chung MK, Clish CB, Correa A, Curran JE, Custer B, Darbar D, Daya M, de Andrade M, DeMeo DL, Dutcher SK, Ellinor PT, Emery LS, Eng C, Fatkin D, Fingerlin T, Forer L, Fornage M, Franceschini N, Fuchsberger C, Fullerton SM, Germer S, Gladwin MT, Gottlieb DJ, Guo X, Hall ME, He J, Heard-Costa NL, Heckbert SR, Irvin MR, Johnsen JM, Johnson AD, Kaplan R, Kardia SLR, Kelly T, Kelly S, Kenny EE, Kiel DP, Klemmer R, Konkle BA, Kooperberg C, Köttgen A, Lange LA, Lasky-Su J, Levy D, Lin X, Lin KH, Liu C, Loos RJF, Garman L, Gerszten R, Lubitz SA, Lunetta KL, Mak ACY, Manichaikul A, Manning AK, Mathias RA, McManus DD, McGarvey ST, Meigs JB, Meyers DA, Mikulla JL, Minear MA, Mitchell BD, Mohanty S, Montasser ME, Montgomery C, Morrison AC, Murabito JM, Natale A, Natarajan P, Nelson SC, North KE, O'Connell JR, Palmer ND, Pankratz N, Peloso GM, Peyser PA, Pleiness J, Post WS, Psaty BM, Rao DC, Redline S, Reiner AP, Roden D, Rotter JI, Ruczinski I, Sarnowski C, Schoenherr S, Schwartz DA, Seo JS, Seshadri S, Sheehan VA, Sheu WH, Shoemaker MB, Smith NL, Smith JA, Sotoodehnia N, Stilp AM, Tang W, Taylor KD, Telen M, Thornton TA, Tracy RP, Van Den Berg DJ, Vasan RS, Viaud-Martinez KA, Vrieze S, Weeks DE, Weir BS, Weiss ST, Weng LC, Willer CJ, Zhang Y, Zhao X, Arnett DK, Ashley-Koch AE, Barnes KC, Boerwinkle E, Gabriel S, Gibbs R, Rice KM, Rich SS, Silverman EK, Qasba P, Gan W, Papanicolaou GJ, Nickerson DA, Browning SR, Zody MC, Zöllner S, Wilson JG, Cupples LA, Laurie CC, Jaquish CE, Hernandez RD, O'Connor TD, Abecasis GR. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature. 2021 02; 590(7845):290-299.View Related Profiles. PMID: 33568819
     
  6. Lioutas VA, Ivan CS, Himali JJ, Aparicio HJ, Leveille T, Romero JR, Beiser AS, Seshadri S. Incidence of Transient Ischemic Attack and Association With Long-term Risk of Stroke. JAMA. 2021 01 26; 325(4):373-381.View Related Profiles. PMID: 33496774; DOI: 10.1001/jama.2020.25071;
     
  7. Wilcock D, Jicha G, Blacker D, Albert MS, D'Orazio LM, Elahi FM, Fornage M, Hinman JD, Knoefel J, Kramer J, Kryscio RJ, Lamar M, Moghekar A, Prestopnik J, Ringman JM, Rosenberg G, Sagare A, Satizabal CL, Schneider J, Seshadri S, Sur S, Tracy RP, Yasar S, Williams V, Singh H, Mazina L, Helmer KG, Corriveau RA, Schwab K, Kivisäkk P, Greenberg SM. MarkVCID cerebral small vessel consortium: I. Enrollment, clinical, fluid protocols. Alzheimers Dement. 2021 Apr; 17(4):704-715.View Related Profiles. PMID: 33480172
     
  8. Shoamanesh A, Akoudad S, Himali JJ, Beiser AS, DeCarli C, Seshadri S, Ikram MA, Romero JR, Vernooij MW. Cortical superficial siderosis in the general population: The Framingham Heart and Rotterdam studies. Int J Stroke. 2021 01 21; 1747493020984559.View Related Profiles. PMID: 33478376; DOI: 10.1177/1747493020984559;
     
  9. Sanchez JS, Becker JA, Jacobs HIL, Hanseeuw BJ, Jiang S, Schultz AP, Properzi MJ, Katz SR, Beiser A, Satizabal CL, O'Donnell A, DeCarli C, Killiany R, El Fakhri G, Normandin MD, Gómez-Isla T, Quiroz YT, Rentz DM, Sperling RA, Seshadri S, Augustinack J, Price JC, Johnson KA. The cortical origin and initial spread of medial temporal tauopathy in Alzheimer's disease assessed with positron emission tomography. Sci Transl Med. 2021 Jan 20; 13(577).View Related Profiles. PMID: 33472953
     
  10. de Erausquin GA, Snyder H, Carrillo M, Hosseini AA, Brugha TS, Seshadri S. The chronic neuropsychiatric sequelae of COVID-19: The need for a prospective study of viral impact on brain functioning. Alzheimers Dement. 2021 Jan 05. PMID: 33399270
     
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