Sudha Seshadri, MD
Adjunct Professor
Boston University Chobanian & Avedisian School of Medicine
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 Chobanian and Avedisian 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 - 08/31/2022 (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


AD Gene Discovery: Exome Chip, New Endophenotypes & Functional studies in CHARGE
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 (Multi-PI)
PI: Sudha Seshadri, MD
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 (Multi-PI)
PI: Sudha Seshadri, MD
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 (Multi-PI)
PI: Sudha Seshadri, MD
NIH/National Institute on Aging
1U01AG052409-01

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

Showing 10 of 23 results. Show All Results


Title


Yr Title Project-Sub Proj Pubs
2023 Interactions of SARS-CoV-2 infection and genetic variation on the risk of cognitive decline and Alzheimer’s disease in Ancestral and Admixed Populations 1U19AG076581-01A1
2023 Multiethnic Validation of VCID biomarkers in South Texas 4U01NS125513-02
2023 South Texas Alzheimer's Disease Center 5P30AG066546-03
2023 South Texas Alzheimer's Disease Center Administrative Core 5P30AG066546-03-6178
2023 South Texas Alzheimer's Disease Center Genetics and Multiomics Core 5P30AG066546-03-6185
2023 Multidimensional Assessment of Brain Health as A Marker of Dementia Risk and Resilience 5R01AG066524-04
2023 Precursors of Stroke Incidence and Prognosis 2R01NS017950-38A1
2022 South Texas Alzheimer's Disease Center 5P30AG066546-02
2022 South Texas Alzheimer's Disease Center Administrative Core 5P30AG066546-02-6178
2022 South Texas Alzheimer's Disease Center Genetics and Multiomics Core 5P30AG066546-02-6185
Showing 10 of 85 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. DeCarli C, Maillard P, Pase MP, Beiser AS, Kojis D, Satizabal CL, Himali JJ, Aparicio HJ, Fletcher E, Seshadri S. Trends in Intracranial and Cerebral Volumes of Framingham Heart Study Participants Born 1930 to 1970. JAMA Neurol. 2024 May 01; 81(5):471-480.View Related Profiles. PMID: 38526486; PMCID: PMC10964161; DOI: 10.1001/jamaneurol.2024.0469;
     
  2. Nadkarni AN, Mukamal KJ, Zhu X, Siscovick D, Brach JS, Jacob M, Seshadri S, Abe T, Rosano C, Djousse L, Rosso AL. Associations of Neurological Biomarkers in Serum With Gait Measures: The Cardiovascular Health Study. J Gerontol A Biol Sci Med Sci. 2024 May 01; 79(5). PMID: 38334311; PMCID: PMC11005783; DOI: 10.1093/gerona/glae043;
     
  3. Melgarejo JD, Patil D, Mena LJ, Vatcheva KP, Garcia JA, Satizabal CL, Chavez CA, Pirela RV, Silva E, Calmon G, Lee JH, Terwilliger JD, Seshadri S, Maestre GE. Association of Variability and Hypertensive Loads in 24-h Blood Pressure With Mortality and Cardiovascular Risk. Am J Hypertens. 2024 Apr 15; 37(5):323-333.View Related Profiles. PMID: 38294177; PMCID: PMC11016833; DOI: 10.1093/ajh/hpae011;
     
  4. Kelly DM, Pinheiro AA, Koini M, Anderson CD, Aparicio H, Hofer E, Kern D, Blacker D, DeCarli C, Hwang SJ, Viswanathan A, Gonzales MM, Beiser AS, Seshadri S, Schmidt R, Demissie S, Romero JR. Impaired Kidney Function, Cerebral Small Vessel Disease and Cognitive Disorders: The Framingham Heart Study. Nephrol Dial Transplant. 2024 Apr 02.View Related Profiles. PMID: 38565317
     
  5. Wang Y, Sarnowski C, Lin H, Pitsillides AN, Heard-Costa NL, Choi SH, Wang D, Bis JC, Blue EE, Boerwinkle E, De Jager PL, Fornage M, Wijsman EM, Seshadri S, Dupuis J, Peloso GM, DeStefano AL. Key variants via the Alzheimer's Disease Sequencing Project whole genome sequence data. Alzheimers Dement. 2024 May; 20(5):3290-3304.View Related Profiles. PMID: 38511601; PMCID: PMC11095439; DOI: 10.1002/alz.13705;
     
  6. Weinstein G, Kojis DJ, Ghosh S, Beiser AS, Seshadri S. Association of Neurotrophic Factors at Midlife With In Vivo Measures of ß-Amyloid and Tau Burden 15 Years Later in Dementia-Free Adults. Neurology. 2024 Apr 09; 102(7):e209198.View Related Profiles. PMID: 38471064; PMCID: PMC11033983; DOI: 10.1212/WNL.0000000000209198;
     
  7. Garbarino VR, Palavicini JP, Melendez J, Barthelemy N, He Y, Kautz TF, Lopez-Cruzan M, Mathews JJ, Xu P, Zhan B, Saliba A, Ragi N, Sharma K, Craft S, Petersen RC, Espindola-Netto JM, Xue A, Tchkonia T, Kirkland JL, Seshadri S, Salardini A, Musi N, Bateman RJ, Gonzales MM, Orr ME. Evaluation of Exploratory Fluid Biomarker Results from a Phase 1 Senolytic Trial in Mild Alzheimer's Disease. Res Sq. 2024 Mar 08. PMID: 38496619; PMCID: PMC10942554; DOI: 10.21203/rs.3.rs-3994894/v1;
     
  8. Sullivan AC, Zuniga G, Ramirez P, Fernandez R, Wang CP, Li J, Davila L, Pelton K, Gomez S, Sohn C, Gonzalez E, Lopez-Cruzan M, Gonzalez DA, Parker A, Zilli E, de Erausquin GA, Seshadri S, Espinoza S, Musi N, Frost B. A pilot study to investigate the safety and feasibility of antiretroviral therapy for Alzheimer's disease (ART-AD). medRxiv. 2024 Feb 28. PMID: 38464267; PMCID: PMC10925371; DOI: 10.1101/2024.02.26.24303316;
     
  9. Krefman AE, Stephen J, Carolan P, Sedaghat S, Mansolf M, Soumare A, Gross AL, Aiello AE, Singh-Manoux A, Ikram MA, Helmer C, Tzourio C, Satizabal C, Levine DA, Lloyd-Jones D, Briceño EM, Sorond FA, Wolters FJ, Himali J, Launer LJ, Zhao L, Haan M, Lopez OL, Debette S, Seshadri S, Judd SE, Hughes TM, Gudnason V, Scholtens D, Allen NB. Cohort Profile: Dementia Risk Prediction Project (DRPP). Int J Epidemiol. 2024 Feb 01; 53(1).View Related Profiles. PMID: 38339864; PMCID: PMC10858348; DOI: 10.1093/ije/dyae012;
     
  10. Pase MP, Himali JJ, Puerta R, Beiser AS, Gonzales MM, Satizabal CL, Yang Q, Aparicio HJ, Kojis DJ, Decarli CS, Lopez OL, Longstreth W, Gudnason V, Mosley TH, Bis JC, Fohner A, Psaty BM, Boada M, García-González P, Valero S, Marquié M, Tracy R, Launer LJ, Ruiz A, Fornage M, Seshadri S. Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia. Neurology. 2024 Feb 27; 102(4):e208075.View Related Profiles. PMID: 38290090
     
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