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




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 Multiethnic Validation of VCID biomarkers in South Texas 1UF1NS125513-01
2021 SARS-CoV-2 and Precursors of Alzheimer's Disease and Related Dementias: An Ultrahigh Field (7T) MRI Study in a Diverse Multinational Cohort 1R56AG074467-01
2021 South Texas Alzheimer's Disease Center 1P30AG066546-01A1
2021 South Texas Alzheimer's Disease Center Genetics and Multiomics Core 1P30AG066546-01A1-6185
2021 South Texas Alzheimer's Disease Center Administrative Core 1P30AG066546-01A1-6178
2021 Multidimensional Assessment of Brain Health as A Marker of Dementia Risk and Resilience 5R01AG066524-02
2021 Therapeutic target discovery in ADSP data via comprehensive whole-genome analysis incorporating ethnic diversity and systems approaches 3U01AG058589-04S1 2
2021 Therapeutic target discovery in ADSP data via comprehensive whole-genome analysis incorporating ethnic diversity and systems approaches 5U01AG058589-04 2
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
Showing 10 of 71 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. Mishra A, Duplaà C, Vojinovic D, Suzuki H, Sargurupremraj M, Zilhão NR, Li S, Bartz TM, Jian X, Zhao W, Hofer E, Wittfeld K, Harris SE, van der Auwera-Palitschka S, Luciano M, Bis JC, Adams HHH, Satizabal CL, Gottesman RF, Gampawar PG, Bülow R, Weiss S, Yu M, Bastin ME, Lopez OL, Vernooij MW, Beiser AS, Völker U, Kacprowski T, Soumare A, Smith JA, Knopman DS, Morris Z, Zhu Y, Rotter JI, Dufouil C, Valdés Hernández M, Muñoz Maniega S, Lathrop M, Boerwinkle E, Schmidt R, Ihara M, Mazoyer B, Yang Q, Joutel A, Tournier-Lasserve E, Launer LJ, Deary IJ, Mosley TH, Amouyel P, DeCarli CS, Psaty BM, Tzourio C, Kardia SLR, Grabe HJ, Teumer A, van Duijn CM, Schmidt H, Wardlaw JM, Ikram MA, Fornage M, Gudnason V, Seshadri S, Matthews PM, Longstreth WT, Couffinhal T, Debette S. Gene-mapping study of extremes of cerebral small vessel disease reveals TRIM47 as a strong candidate. Brain. 2022 Jun 30; 145(6):1992-2007.View Related Profiles. PMID: 35511193
     
  2. Oelsner EC, Krishnaswamy A, Balte PP, Allen NB, Ali T, Anugu P, Andrews HF, Arora K, Asaro A, Barr RG, Bertoni AG, Bon J, Boyle R, Chang AA, Chen G, Coady S, Cole SA, Coresh J, Cornell E, Correa A, Couper D, Cushman M, Demmer RT, Elkind MSV, Folsom AR, Fretts AM, Gabriel KP, Gallo LC, Gutierrez J, Han MLK, Henderson JM, Howard VJ, Isasi CR, Jacobs DR, Judd SE, Mukaz DK, Kanaya AM, Kandula NR, Kaplan RC, Kinney GL, Kucharska-Newton A, Lee JS, Lewis CE, Levine DA, Levitan EB, Levy BD, Make BJ, Malloy K, Manly JJ, Mendoza-Puccini C, Meyer KA, Min YN, Moll MR, Moore WC, Mauger D, Ortega VE, Palta P, Parker MM, Phipatanakul W, Post WS, Postow L, 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 KE, Wenzel SE, Winters K, Woodruff PG, Xanthakis V, Zhang Y, Zhang Y. Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design. Am J Epidemiol. 2022 Jun 27; 191(7):1153-1173.View Related Profiles. PMID: 35279711; PMCID: PMC8992336; DOI: 10.1093/aje/kwac032;
     
  3. Sala-Vila A, Satizabal CL, Tintle N, Melo van Lent D, Vasan RS, Beiser AS, Seshadri S, Harris WS. Red Blood Cell DHA Is Inversely Associated with Risk of Incident Alzheimer's Disease and All-Cause Dementia: Framingham Offspring Study. Nutrients. 2022 Jun 09; 14(12).View Related Profiles. PMID: 35745137; PMCID: PMC9228504; DOI: 10.3390/nu14122408;
     
  4. Cooper LL, O'Donnell A, Beiser AS, Thibault EG, Sanchez JS, Benjamin EJ, Hamburg NM, Vasan RS, Larson MG, Johnson KA, Mitchell GF, Seshadri S. Association of Aortic Stiffness and Pressure Pulsatility With Global Amyloid-ß and Regional Tau Burden Among Framingham Heart Study Participants Without Dementia. JAMA Neurol. 2022 Jun 06.View Related Profiles. PMID: 35666520
     
  5. Tarko L, Costa L, Galloway A, Ho YL, Gagnon D, Lioutas V, Seshadri S, Cho K, Wilson P, Aparicio HJ. Racial and Ethnic Differences in Short- and Long-term Mortality by Stroke Type. Neurology. 2022 Jun 01.View Related Profiles. PMID: 35649728
     
  6. Tannous J, Pan A, Bako A, Potter T, Jones SL, Janjan N, Smith ML, Seshadri S, Ory MG, Vahidy FS. COVID-19 associated disruptions in routine health care of people with mild cognitive impairment or dementia. Alzheimers Dement (Amst). 2022; 14(1):e12323. PMID: 35664890; PMCID: PMC9157405; DOI: 10.1002/dad2.12323;
     
  7. Toledo JB, Liu H, Grothe MJ, Rashid T, Launer L, Shaw LM, Snoussi H, Heckbert S, Weiner M, Trojanwoski JQ, Seshadri S, Habes M. Disentangling tau and brain atrophy cluster heterogeneity across the Alzheimer's disease continuum. Alzheimers Dement (N Y). 2022; 8(1):e12305. PMID: 35619830; PMCID: PMC9127251; DOI: 10.1002/trc2.12305;
     
  8. McGrath ER, Beiser AS, O'Donnell A, Himali JJ, Pase MP, Satizabal CL, Seshadri S. Determining Vascular Risk Factors for Dementia and Dementia Risk Prediction Across Mid- to Later-Life: The Framingham Heart Study. Neurology. 2022 May 18.View Related Profiles. PMID: 35584926; DOI: 10.1212/WNL.0000000000200521;
     
  9. Buckley RF, O'Donnell A, McGrath ER, Jacobs HIL, Lois C, Satizabal CL, Ghosh S, Rubinstein ZB, Murabito JM, Sperling RA, Johnson KA, Seshadri S, Beiser AS. Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study. Ann Neurol. 2022 Jul; 92(1):11-22.View Related Profiles. PMID: 35471588; PMCID: PMC9233144; DOI: 10.1002/ana.26382;
     
  10. Trpchevska N, Freidin MB, Broer L, Oosterloo BC, Yao S, Zhou Y, Vona B, Bishop C, Bizaki-Vallaskangas A, Canlon B, Castellana F, Chasman DI, Cherny S, Christensen K, Concas MP, Correa A, Elkon R, Mengel-From J, Gao Y, Giersch ABS, Girotto G, Gudjonsson A, Gudnason V, Heard-Costa NL, Hertzano R, Hjelmborg JVB, Hjerling-Leffler J, Hoffman HJ, Kaprio J, Kettunen J, Krebs K, Kähler AK, Lallemend F, Launer LJ, Lee IM, Leonard H, Li CM, Lowenheim H, Magnusson PKE, van Meurs J, Milani L, Morton CC, Mäkitie A, Nalls MA, Nardone GG, Nygaard M, Palviainen T, Pratt S, Quaranta N, Rämö J, Saarentaus E, Sardone R, Satizabal CL, Schweinfurth JM, Seshadri S, Shiroma E, Shulman E, Simonsick E, Spankovich C, Tropitzsch A, Lauschke VM, Sullivan PF, Goedegebure A, Cederroth CR, Williams FMK, Nagtegaal AP. Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss. Am J Hum Genet. 2022 Jun 02; 109(6):1077-1091.View Related Profiles. PMID: 35580588
     
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