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 (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
2022 South Texas Alzheimer's Disease Center Administrative Core 5P30AG066546-02-6178
2022 South Texas Alzheimer's Disease Center 5P30AG066546-02
2022 South Texas Alzheimer's Disease Center Genetics and Multiomics Core 5P30AG066546-02-6185
2022 Multidimensional Assessment of Brain Health as A Marker of Dementia Risk and Resilience 5R01AG066524-03
2022 Therapeutic target discovery in ADSP data via comprehensive whole-genome analysis incorporating ethnic diversity and systems approaches 5U01AG058589-05
2021 Multiethnic Validation of VCID biomarkers in South Texas 1UF1NS125513-01
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 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
Showing 10 of 76 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. Zhang Y, Liu X, Wiggins KL, Kurniansyah N, Guo X, Rodrigue AL, Zhao W, Yanek LR, Ratliff SM, Pitsillides A, Aguirre Patiño JS, Sofer T, Arking DE, Austin TR, Beiser AS, Blangero J, Boerwinkle E, Bressler J, Curran JE, Hou L, Hughes TM, Kardia SL, Launer L, Levy D, Mosley TH, Nasrallah IM, Rich SS, Rotter JI, Seshadri S, Tarraf W, González KA, Ramachandran V, Yaffe K, Nyquist PA, Psaty BM, DeCarli CS, Smith JA, Glahn DC, González HM, Bis JC, Fornage M, Heckbert SR, Fitzpatrick AL, Liu C, Satizabal CL. Association of Mitochondrial DNA Copy Number With Brain MRI Markers and Cognitive Function: A Meta-analysis of Community-Based Cohorts. Neurology. 2023 Mar 16.View Related Profiles. PMID: 36927883
     
  2. Maestre G, Carrillo M, Kalaria R, Acosta D, Adams L, Adoukonou T, Akinwande K, Akinyemi J, Akinyemi R, Akpa O, Alladi S, Allegri R, Arizaga R, Arshad F, Arulogun O, Babalola D, Baiyewu O, Bak T, Bellaj T, Boshe J, Brayne C, Brodie-Mends D, Brown R, Cahn J, Cyrille N, Damasceno A, de Silva R, de Silva R, Djibuti M, Dreyer AJ, Ellajosyula R, Farombi T, Fongang B, Forner S, Friedland R, Garza N, Gbessemehlan A, Georgiou EE, Gouider R, Govia I, Grinberg L, Guerchet M, Gugssa S, Gumikiriza-Onoria JL, Gustafson D, Hogervorst E, Hornberger M, Ibanez A, Ihara M, Ismail O, Issac T, Jönsson L, Kaputu C, Karanja W, Karungi J, Tshala-Katumbay D, Kunkle B, Lee JH, Leroi I, Lewis R, Livingston G, Lopera F, Lwere K, Manes F, Mbakile-Mahlanza L, Mena P, Miller B, Millogo A, Mohamed A, Musyimi C, Mutiso V, Nakasujja N, Ndetei D, Nightingale S, Njamnshi AK, Novotni G, Nyamayaro P, Nyame S, Ogeng'o J, Ogunniyi A, Okada De Oliveira M, Okubadejo N, Orrell M, Orunmuyi A, Owolabi M, Paddick S, A Pericak-Vance M, Pirtosek Z, Potocnik F, Preston B, Raman R, Ranchod K, Rizig M, Rosselli M, Deepa R, Roy U, Salokhiddinov M, Sano M, Sarfo F, Satizabal CL, Sepulveda-Falla D, Seshadri S, Sexton C, Skoog I, St George-Hyslop P, Suemoto C, Tanner J, Thapa P, Toure K, Ucheagwu V, Udeh-Momoh C, Valcour V, Vance J, Varghese M, Vera J, Walker R, Weidner W, Sebastian W, Whitehead Gay P, Zetterberg H, Zewde Y. The Nairobi Declaration-Reducing the burden of dementia in low- and middle-income countries (LMICs): Declaration of the 2022 Symposium on Dementia and Brain Aging in LMICs. Alzheimers Dement. 2023 Mar 11.View Related Profiles. PMID: 36905253
     
  3. Rashid T, Li K, Toledo JB, Nasrallah I, Pajewski NM, Dolui S, Detre J, Wolk DA, Liu H, Heckbert SR, Bryan RN, Williamson J, Davatzikos C, Seshadri S, Launer LJ, Habes M. Association of Intensive vs Standard Blood Pressure Control With Regional Changes in Cerebral Small Vessel Disease Biomarkers: Post Hoc Secondary Analysis of the SPRINT MIND Randomized Clinical Trial. JAMA Netw Open. 2023 Mar 01; 6(3):e231055. PMID: 36857053; PMCID: PMC9978954; DOI: 10.1001/jamanetworkopen.2023.1055;
     
  4. Nichols E, Merrick R, Hay SI, Himali D, Himali JJ, Hunter S, Keage HAD, Latimer CS, Scott MR, Steinmetz JD, Walker JM, Wharton SB, Wiedner CD, Crane PK, Keene CD, Launer LJ, Matthews FE, Schneider J, Seshadri S, White L, Brayne C, Vos T. The prevalence, correlation, and co-occurrence of neuropathology in old age: harmonisation of 12 measures across six community-based autopsy studies of dementia. Lancet Healthy Longev. 2023 Mar; 4(3):e115-e125.View Related Profiles. PMID: 36870337; PMCID: PMC9977689; DOI: 10.1016/S2666-7568(23)00019-3;
     
  5. Hinman JD, Elahi F, Chong D, Radabaugh H, Ferguson A, Maillard P, Thompson JF, Rosenberg GA, Sagare A, Moghekar A, Lu H, Lee T, Wilcock D, Satizabal CL, Tracy R, Seshadri S, Schwab K, Helmer K, Singh H, Kivisäkk P, Greenberg S, DeCarli C, Kramer J. Placental growth factor as a sensitive biomarker for vascular cognitive impairment. Alzheimers Dement. 2023 Feb 23.View Related Profiles. PMID: 36815663
     
  6. Charisis S, Lin H, Ray R, Joehanes R, Beiser AS, Levy D, Seshadri S, Sargurupremraj M, Satizabal CL. Obesity impacts the expression of Alzheimer's disease-related genes: The Framingham Heart Study. Alzheimers Dement. 2023 Feb 22.View Related Profiles. PMID: 36811231; DOI: 10.1002/alz.12954;
     
  7. Yang Y, Knol MJ, Wang R, Mishra A, Liu D, Luciano M, Teumer A, Armstrong N, Bis JC, Jhun MA, Li S, Adams HHH, Aziz NA, Bastin ME, Bourgey M, Brody JA, Frenzel S, Gottesman RF, Hosten N, Hou L, Kardia SLR, Lohner V, Marquis P, Maniega SM, Satizabal CL, Sorond FA, Valdés Hernández MC, van Duijn CM, Vernooij MW, Wittfeld K, Yang Q, Zhao W, Boerwinkle E, Levy D, Deary IJ, Jiang J, Mather KA, Mosley TH, Psaty BM, Sachdev PS, Smith JA, Sotoodehnia N, DeCarli CS, Breteler MMB, Ikram MA, Grabe HJ, Wardlaw J, Longstreth WT, Launer LJ, Seshadri S, Debette S, Fornage M. Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI. Brain. 2023 Feb 13; 146(2):492-506.View Related Profiles. PMID: 35943854; PMCID: PMC9924914; DOI: 10.1093/brain/awac290;
     
  8. de Rojas I, Moreno-Grau S, Tesi N, Grenier-Boley B, Andrade V, Jansen IE, Pedersen NL, Stringa N, Zettergren A, Hernández I, Montrreal L, Antúnez C, Antonell A, Tankard RM, Bis JC, Sims R, Bellenguez C, Quintela I, González-Perez A, Calero M, Franco-Macías E, Macías J, Blesa R, Cervera-Carles L, Menéndez-González M, Frank-García A, Royo JL, Moreno F, Huerto Vilas R, Baquero M, Diez-Fairen M, Lage C, García-Madrona S, García-González P, Alarcón-Martín E, Valero S, Sotolongo-Grau O, Ullgren A, Naj AC, Lemstra AW, Benaque A, Pérez-Cordón A, Benussi A, Rábano A, Padovani A, Squassina A, de Mendonça A, Arias Pastor A, Kok AAL, Meggy A, Pastor AB, Espinosa A, Corma-Gómez A, Martín Montes A, Sanabria Á, DeStefano AL, Schneider A, Haapasalo A, Kinhult Ståhlbom A, Tybjærg-Hansen A, Hartmann AM, Spottke A, Corbatón-Anchuelo A, Rongve A, Borroni B, Arosio B, Nacmias B, Nordestgaard BG, Kunkle BW, Charbonnier C, Abdelnour C, Masullo C, Martínez Rodríguez C, Muñoz-Fernandez C, Dufouil C, Graff C, Ferreira CB, Chillotti C, Reynolds CA, Fenoglio C, Van Broeckhoven C, Clark C, Pisanu C, Satizabal CL, Holmes C, Buiza-Rueda D, Aarsland D, Rujescu D, Alcolea D, Galimberti D, Wallon D, Seripa D, Grünblatt E, Dardiotis E, Düzel E, Scarpini E, Conti E, Rubino E, Gelpi E, Rodriguez-Rodriguez E, Duron E, Boerwinkle E, Ferri E, Tagliavini F, Küçükali F, Pasquier F, Sanchez-Garcia F, Mangialasche F, Jessen F, Nicolas G, Selbæk G, Ortega G, Chêne G, Hadjigeorgiou G, Rossi G, Spalletta G, Giaccone G, Grande G, Binetti G, Papenberg G, Hampel H, Bailly H, Zetterberg H, Soininen H, Karlsson IK, Alvarez I, Appollonio I, Giegling I, Skoog I, Saltvedt I, Rainero I, Rosas Allende I, Hort J, Diehl-Schmid J, Van Dongen J, Vidal JS, Lehtisalo J, Wiltfang J, Thomassen JQ, Kornhuber J, Haines JL, Vogelgsang J, Pineda JA, Fortea J, Popp J, Deckert J, Buerger K, Morgan K, Fließbach K, Sleegers K, Molina-Porcel L, Kilander L, Weinhold L, Farrer LA, Wang LS, Kleineidam L, Farotti L, Parnetti L, Tremolizzo L, Hausner L, Benussi L, Froelich L, Ikram MA, Deniz-Naranjo MC, Tsolaki M, Rosende-Roca M, Löwenmark M, Hulsman M, Spallazzi M, Pericak-Vance MA, Esiri M, Bernal Sánchez-Arjona M, Dalmasso MC, Martínez-Larrad MT, Arcaro M, Nöthen MM, Fernández-Fuertes M, Dichgans M, Ingelsson M, Herrmann MJ, Scherer M, Vyhnalek M, Kosmidis MH, Yannakoulia M, Schmid M, Ewers M, Heneka MT, Wagner M, Scamosci M, Kivipelto M, Hiltunen M, Zulaica M, Alegret M, Fornage M, Roberto N, van Schoor NM, Seidu NM, Banaj N, Armstrong NJ, Scarmeas N, Scherbaum N, Goldhardt O, Hanon O, Peters O, Skrobot OA, Quenez O, Lerch O, Bossù P, Caffarra P, Dionigi Rossi P, Sakka P, Mecocci P, Hoffmann P, Holmans PA, Fischer P, Riederer P, Yang Q, Marshall R, Kalaria RN, Mayeux R, Vandenberghe R, Cecchetti R, Ghidoni R, Frikke-Schmidt R, Sorbi S, Hägg S, Engelborghs S, Helisalmi S, Botne Sando S, Kern S, Archetti S, Boschi S, Fostinelli S, Gil S, Mendoza S, Mead S, Ciccone S, Djurovic S, Heilmann-Heimbach S, Riedel-Heller S, Kuulasmaa T, Del Ser T, Lebouvier T, Polak T, Ngandu T, Grimmer T, Bessi V, Escott-Price V, Giedraitis V, Deramecourt V, Maier W, Jian X, Pijnenburg YAL, Kehoe PG, Garcia-Ribas G, Sánchez-Juan P, Pastor P, Pérez-Tur J, Piñol-Ripoll G, Lopez de Munain A, García-Alberca JM, Bullido MJ, Álvarez V, Lleó A, Real LM, Mir P, Medina M, Scheltens P, Holstege H, Marquié M, Sáez ME, Carracedo Á, Amouyel P, Schellenberg GD, Williams J, Seshadri S, van Duijn CM, Mather KA, Sánchez-Valle R, Serrano-Ríos M, Orellana A, Tárraga L, Blennow K, Huisman M, Andreassen OA, Posthuma D, Clarimón J, Boada M, van der Flier WM, Ramirez A, Lambert JC, van der Lee SJ, Ruiz A. Author Correction: Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. Nat Commun. 2023 Feb 09; 14(1):716.View Related Profiles. PMID: 36759603; PMCID: PMC9911386; DOI: 10.1038/s41467-023-36192-x;
     
  9. Shulman D, Dubnov S, Zorbaz T, Madrer N, Paldor I, Bennett DA, Seshadri S, Mufson EJ, Greenberg DS, Loewenstein Y, Soreq H. Sex-specific declines in cholinergic-targeting tRNA fragments in the nucleus accumbens in Alzheimer's disease. bioRxiv. 2023 Feb 08. PMID: 36798311; PMCID: PMC9934682; DOI: 10.1101/2023.02.08.527612;
     
  10. Wang D, Honnorat N, Fox PT, Ritter K, Eickhoff SB, Seshadri S, Habes M. Deep neural network heatmaps capture Alzheimer's disease patterns reported in a large meta-analysis of neuroimaging studies. Neuroimage. 2023 Apr 01; 269:119929. PMID: 36740029
     
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