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
2020 Precursors of Stroke Incidence and Prognosis 5R01NS017950-37 621
2020 Precursors of Stroke Incidence and Prognosis 5R01NS017950-37 621
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
2019 Precursors of Stroke Incidence and Prognosis 5R01NS017950-36 621
2019 Microglial, Inflammatory and Omics Markers of Cerebral Small Vessel Disease in the CHARGE Consortium 5UH3NS100605-04 24
2019 Temporal Trends, Novel Imaging and Molecular Characterization of Preclinical and Clinical Alzheimer's Disease in the Framingham Cohorts 5R01AG054076-04 83
2019 ADSP Follow-up in Multi-Ethnic Cohorts via Endophenotypes, Omics & Model Systems 5U01AG052409-03 55
2019 Preclinical AD: Correlates of Amyloid, Tau PET and fcMRI in Framingham Gen 3 Young Adults 5R01AG049607-05 43
2019 MRI, Cognitive, Genetic and Biomarker Precursors of AD & Dementia in Young Adults 5R01AG033040-10 58
Showing 10 of 57 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. 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. 2020 Aug 29.View Related Profiles. PMID: 32860698
     
  2. Sliz E, Shin J, Syme C, Black S, Seshadri S, Paus T, Pausova Z. Thickness of the cerebral cortex shows positive association with blood levels of triacylglycerols carrying 18-carbon fatty acids. Commun Biol. 2020 Aug 20; 3(1):456. PMID: 32820227
     
  3. Bis JC, Jian X, Kunkle BW, Chen Y, Hamilton-Nelson KL, Bush WS, Salerno WJ, Lancour D, Ma Y, Renton AE, Marcora E, Farrell JJ, Zhao Y, Qu L, Ahmad S, Amin N, Amouyel P, Beecham GW, Below JE, Campion D, Cantwell L, Charbonnier C, Chung J, Crane PK, Cruchaga C, Cupples LA, Dartigues JF, Debette S, Deleuze JF, Fulton L, Gabriel SB, Genin E, Gibbs RA, Goate A, Grenier-Boley B, Gupta N, Haines JL, Havulinna AS, Helisalmi S, Hiltunen M, Howrigan DP, Ikram MA, Kaprio J, Konrad J, Kuzma A, Lander ES, Lathrop M, Lehtimäki T, Lin H, Mattila K, Mayeux R, Muzny DM, Nasser W, Neale B, Nho K, Nicolas G, Patel D, Pericak-Vance MA, Perola M, Psaty BM, Quenez O, Rajabli F, Redon R, Reitz C, Remes AM, Salomaa V, Sarnowski C, Schmidt H, Schmidt M, Schmidt R, Soininen H, Thornton TA, Tosto G, Tzourio C, van der Lee SJ, van Duijn CM, Valladares O, Vardarajan B, Wang LS, Wang W, Wijsman E, Wilson RK, Witten D, Worley KC, Zhang X, Bellenguez C, Lambert JC, Kurki MI, Palotie A, Daly M, Boerwinkle E, Lunetta KL, Destefano AL, Dupuis J, Martin ER, Schellenberg GD, Seshadri S, Naj AC, Fornage M, Farrer LA. Correction: Whole exome sequencing study identifies novel rare and common Alzheimer's-Associated variants involved in immune response and transcriptional regulation. Mol Psychiatry. 2020 Aug; 25(8):1901-1903.View Related Profiles. PMID: 31636380
     
  4. Petrea RE, O'Donnell A, Beiser AS, Habes M, Aparicio H, DeCarli C, Seshadri S, Romero JR. Mid to Late Life Hypertension Trends and Cerebral Small Vessel Disease in the Framingham Heart Study. Hypertension. 2020 Sep; 76(3):707-714.View Related Profiles. PMID: 32755403
     
  5. Peloso GM, Beiser AS, Satizabal CL, Xanthakis V, Vasan RS, Pase MP, Destefano AL, Seshadri S. Cardiovascular health, genetic risk, and risk of dementia in the Framingham Heart Study. Neurology. 2020 Sep 08; 95(10):e1341-e1350.View Related Profiles. PMID: 32690788
     
  6. Du Y, Paiva K, Cebula A, Kim S, Lopez K, Li C, White C, Myneni S, Seshadri S, Wang J. Diabetes-Related Topics in an Online Forum for Caregivers of Individuals Living With Alzheimer Disease and Related Dementias: Qualitative Inquiry. J Med Internet Res. 2020 Jul 06; 22(7):e17851. PMID: 32628119
     
  7. Wolters FJ, Chibnik LB, Waziry R, Anderson R, Berr C, Beiser A, Bis JC, Blacker D, Bos D, Brayne C, Dartigues JF, Darweesh SKL, Davis-Plourde KL, de Wolf F, Debette S, Dufouil C, Fornage M, Goudsmit J, Grasset L, Gudnason V, Hadjichrysanthou C, Helmer C, Ikram MA, Ikram MK, Joas E, Kern S, Kuller LH, Launer L, Lopez OL, Matthews FE, McRae-McKee K, Meirelles O, Mosley TH, Pase MP, Psaty BM, Satizabal CL, Seshadri S, Skoog I, Stephan BCM, Wetterberg H, Wong MM, Zettergren A, Hofman A. Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium. Neurology. 2020 Aug 04; 95(5):e519-e531.View Related Profiles. PMID: 32611641
     
  8. Romero JR, Demissie S, Beiser A, Himali JJ, DeCarli C, Levy D, Seshadri S. Relation of plasma ß-amyloid, clusterin, and tau with cerebral microbleeds: Framingham Heart Study. Ann Clin Transl Neurol. 2020 Jul; 7(7):1083-1091.View Related Profiles. PMID: 32588552
     
  9. Armstrong NJ, Mather KA, Sargurupremraj M, Knol MJ, Malik R, Satizabal CL, Yanek LR, Wen W, Gudnason VG, Dueker ND, Elliott LT, Hofer E, Bis J, Jahanshad N, Li S, Logue MA, Luciano M, Scholz M, Smith AV, Trompet S, Vojinovic D, Xia R, Alfaro-Almagro F, Ames D, Amin N, Amouyel P, Beiser AS, Brodaty H, Deary IJ, Fennema-Notestine C, Gampawar PG, Gottesman R, Griffanti L, Jack CR, Jenkinson M, Jiang J, Kral BG, Kwok JB, Lampe L, C M Liewald D, Maillard P, Marchini J, Bastin ME, Mazoyer B, Pirpamer L, Rafael Romero J, Roshchupkin GV, Schofield PR, Schroeter ML, Stott DJ, Thalamuthu A, Trollor J, Tzourio C, van der Grond J, Vernooij MW, Witte VA, Wright MJ, Yang Q, Morris Z, Siggurdsson S, Psaty B, Villringer A, Schmidt H, Haberg AK, van Duijn CM, Jukema JW, Dichgans M, Sacco RL, Wright CB, Kremen WS, Becker LC, Thompson PM, Mosley TH, Wardlaw JM, Ikram MA, Adams HHH, Seshadri S, Sachdev PS, Smith SM, Launer L, Longstreth W, DeCarli C, Schmidt R, Fornage M, Debette S, Nyquist PA. Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities. Stroke. 2020 Jul; 51(7):2111-2121.View Related Profiles. PMID: 32517579
     
  10. Lioutas VA, Beiser AS, Aparicio HJ, Himali JJ, Selim MH, Romero JR, Seshadri S. Assessment of Incidence and Risk Factors of Intracerebral Hemorrhage Among Participants in the Framingham Heart Study Between 1948 and 2016. JAMA Neurol. 2020 Jun 08.View Related Profiles. PMID: 32511690
     
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