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 Multiethnic Validation of VCID biomarkers in South Texas 1UF1NS125513-01
2021 South Texas Alzheimer's Disease Center Administrative Core 1P30AG066546-01A1-6178
2021 South Texas Alzheimer's Disease Center Genetics and Multiomics Core 1P30AG066546-01A1-6185
2021 South Texas Alzheimer's Disease Center 1P30AG066546-01A1
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 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 3U01AG058589-03S1 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 3U01AG058589-04S1 2
2020 Multidimensional Assessment of Brain Health as A Marker of Dementia Risk and Resilience 1R01AG066524-01A1
Showing 10 of 72 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. Papadopoulos A, Palaiopanos K, Björkbacka H, Peters A, de Lemos JA, Seshadri S, Dichgans M, Georgakis MK. Circulating Interleukin-6 Levels and Incident Ischemic Stroke: A Systematic Review and Meta-analysis of Prospective Studies. Neurology. 2021 Dec 30. PMID: 34969940
     
  2. McGrath ER, Himali JJ, Levy D, Yang Q, DeCarli CS, Courchesne P, Satizabal CL, Finney R, Vasan RS, Beiser AS, Seshadri S. Plasma EFEMP1 Is Associated with Brain Aging and Dementia: The Framingham Heart Study. J Alzheimers Dis. 2021 Dec 20.View Related Profiles. PMID: 34958018; DOI: 10.3233/JAD-215053;
     
  3. Fohner AE, Bartz TM, Tracy RP, Adams HHH, Bis JC, Djousse L, Satizabal CL, Lopez OL, Seshadri S, Mukamal KJ, Kuller LH, Psaty BM, Longstreth WT. Association of Serum Neurofilament Light Chain Concentration and MRI Findings in Older Adults: The Cardiovascular Health Study. Neurology. 2021 Dec 17.View Related Profiles. PMID: 34921102
     
  4. Bressler J, Davies G, Smith AV, Saba Y, Bis JC, Jian X, Hayward C, Yanek L, Smith JA, Mirza SS, Wang R, Adams HHH, Becker D, Boerwinkle E, Campbell A, Cox SR, Eiriksdottir G, Fawns-Ritchie C, Gottesman RF, Grove ML, Guo X, Hofer E, Kardia SLR, Knol MJ, Koini M, Lopez OL, Marioni RE, Nyquist P, Pattie A, Polasek O, Porteous DJ, Rudan I, Satizabal CL, Schmidt H, Schmidt R, Sidney S, Simino J, Smith BH, Turner ST, van der Lee SJ, Ware EB, Whitmer RA, Yaffe K, Yang Q, Zhao W, Gudnason V, Launer LJ, Fitzpatrick AL, Psaty BM, Fornage M, Arfan Ikram M, van Duijn CM, Seshadri S, Mosley TH, Deary IJ. Association of low-frequency and rare coding variants with information processing speed. Transl Psychiatry. 2021 Dec 04; 11(1):613.View Related Profiles. PMID: 34864818; PMCID: PMC8643353; DOI: 10.1038/s41398-021-01736-6;
     
  5. Ramos-Cejudo J, Johnson AD, Beiser A, Seshadri S, Salinas J, Berger JS, Fillmore NR, Do N, Zheng C, Kovbasyuk Z, Ardekani BA, Bubu OM, Parekh A, Convit A, Betensky RA, Wisniewski TM, Osorio RS. The Neutrophil to Lymphocyte Ratio Is Associated With the Risk of Subsequent Dementia in the Framingham Heart Study. Front Aging Neurosci. 2021; 13:773984.View Related Profiles. PMID: 34916927; PMCID: PMC8670436; DOI: 10.3389/fnagi.2021.773984;
     
  6. Spartano NL, Himali JJ, Trinquart L, Yang Q, Weinstein G, Satizabal CL, Dukes KA, Beiser AS, Murabito JM, Vasan RS, Seshadri S. Accelerometer-Measured, Habitual Physical Activity and Circulating Brain-Derived Neurotrophic Factor: A Cross-Sectional Study. J Alzheimers Dis. 2021 Nov 29.View Related Profiles. PMID: 34864673; DOI: 10.3233/JAD-215109;
     
  7. Liu P, Jiang D, Albert M, Bauer CE, Caprihan A, Gold BT, Greenberg SM, Helmer KG, Jann K, Jicha G, Rodriguez P, Satizabal CL, Seshadri S, Singh H, Thompson JF, Wang DJJ, Lu H. Multi-vendor and multisite evaluation of cerebrovascular reactivity mapping using hypercapnia challenge. Neuroimage. 2021 12 15; 245:118754.View Related Profiles. PMID: 34826595
     
  8. Stefanidou M, Himali JJ, Devinsky O, Romero JR, Ikram MA, Beiser AS, Seshadri S, Friedman D. Vascular risk factors as predictors of epilepsy in older age: The Framingham Heart Study. Epilepsia. 2022 Jan; 63(1):237-243.View Related Profiles. PMID: 34786697; DOI: 10.1111/epi.17108;
     
  9. Bhattacharya R, Zekavat SM, Haessler J, Fornage M, Raffield L, Uddin MM, Bick AG, Niroula A, Yu B, Gibson C, Griffin G, Morrison AC, Psaty BM, Longstreth WT, Bis JC, Rich SS, Rotter JI, Tracy RP, Correa A, Seshadri S, Johnson A, Collins JM, Hayden KM, Madsen TE, Ballantyne CM, Jaiswal S, Ebert BL, Kooperberg C, Manson JE, Whitsel EA, Natarajan P, Reiner AP. Clonal Hematopoiesis Is Associated With Higher Risk of Stroke. Stroke. 2021 Nov 08; STROKEAHA121037388. PMID: 34743536
     
  10. Hu Y, Haessler JW, Manansala R, Wiggins KL, Moscati A, Beiser A, Heard-Costa NL, Sarnowski C, Raffield LM, Chung J, Marini S, Anderson CD, Rosand J, Xu H, Sun X, Kelly TN, Wong Q, Lange LA, Rotter JI, Correa A, Vasan RS, Seshadri S, Rich SS, Do R, Loos RJF, Longstreth WT, Bis JC, Psaty BM, Tirschwell DL, Assimes TL, Silver B, Liu S, Jackson R, Wassertheil-Smoller S, Mitchell BD, Fornage M, Auer PL, Reiner AP, Kooperberg C. Whole-Genome Sequencing Association Analyses of Stroke and Its Subtypes in Ancestrally Diverse Populations From Trans-Omics for Precision Medicine Project. Stroke. 2021 Nov 03; STROKEAHA120031792.View Related Profiles. PMID: 34727735
     
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