Sudha Seshadri, MD
Adjunct Professor, Neurology
Biography
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.
Other Positions
- Investigator, Framingham Heart Study
- Director, Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, UT Health San Antonio
Education
- All India Institute of Medical Science (AIIMS), MD
- Christian Medical College & Hospital, MBBS
- All India Institute of Medical Science (AIIMS), DM
Publications
- Published on 12/18/2024
Kern KC, Vohra M, Thirion ML, Wang DJJ, Wilcock DM, Thompson JF, Rosenberg GA, Sagare A, Moghekar A, Lu H, Lee T, Elahi FM, Satizabal CL, Tracy R, Seshadri S, Schwab K, Helmer K, Singh H, Kivisäkk P, Greenberg SM, Vossel K, Kramer JH, Maillard P, DeCarli CS, Hinman JD. White matter free water mediates the associations between placental growth factor, white matter hyperintensities, and cognitive status. Alzheimers Dement. 2024 Dec 18. PMID: 39692213.
Read at: PubMed - Published on 12/16/2024
Hou J, Hess JL, Zhang C, van Rooij JGJ, Hearn GC, Fan CC, Faraone SV, Fennema-Notestine C, Lin SJ, Escott-Price V, Seshadri S, Holmans P, Tsuang MT, Kremen WS, Gaiteri C, Glatt SJ. Meta-Analysis of Transcriptomic Studies of Blood and Six Brain Regions Identifies a Consensus of 15 Cross-Tissue Mechanisms in Alzheimer's Disease and Suggests an Origin of Cross-Study Heterogeneity. Am J Med Genet B Neuropsychiatr Genet. 2024 Dec 16; e33019. PMID: 39679839.
Read at: PubMed - Published on 12/9/2024
Wang D, Honnorat N, Toledo JB, Li K, Charisis S, Rashid T, Benet Nirmala A, Brandigampala SR, Mojtabai M, Seshadri S, Habes M. Deep learning reveals pathology-confirmed neuroimaging signatures in Alzheimer's, vascular and Lewy body dementias. Brain. 2024 Dec 09. PMID: 39657969.
Read at: PubMed - Published on 12/6/2024
van Lent DM, Mesa HG, Short MI, Gonzales MM, Aparicio HJ, Salinas J, Yuan C, Jacques PF, Beiser A, Seshadri S, Jacob ME, Himali JJ. Association between dietary inflammatory index score and incident dementia. Alzheimers Dement. 2024 Dec 06. PMID: 39641390.
Read at: PubMed - Published on 12/4/2024
Le Borgne J, Gomez L, Heikkinen S, Amin N, Ahmad S, Choi SH, Bis J, Grenier-Boley B, Rodriguez OG, Kleineidam L, Young J, Tripathi KP, Wang L, Varma A, Campos-Martin R, van der Lee S, Damotte V, de Rojas I, Palmal S, Lipton R, Reiman E, McKee A, De Jager P, Bush W, Small S, Levey A, Saykin A, Foroud T, Albert M, Hyman B, Petersen R, Younkin S, Sano M, Wisniewski T, Vassar R, Schneider J, Henderson V, Roberson E, DeCarli C, LaFerla F, Brewer J, Swerdlow R, Van Eldik L, Hamilton-Nelson K, Paulson H, Naj A, Lopez O, Chui H, Crane P, Grabowski T, Kukull W, Asthana S, Craft S, Strittmatter S, Cruchaga C, Leverenz J, Goate A, Kamboh MI, George-Hyslop PS, Valladares O, Kuzma A, Cantwell L, Riemenschneider M, Morris J, Slifer S, Dalmasso C, Castillo A, Küçükali F, Peters O, Schneider A, Dichgans M, Rujescu D, Scherbaum N, Deckert J, Riedel-Heller S, Hausner L, Molina-Porcel L, Düzel E, Grimmer T, Wiltfang J, Heilmann-Heimbach S, Moebus S, Tegos T, Scarmeas N, Dols-Icardo O, Moreno F, Pérez-Tur J, Bullido MJ, Pastor P, Sánchez-Valle R, Álvarez V, Boada M, García-González P, Puerta R, Mir P, Real LM, Piñol-Ripoll G, García-Alberca JM, Royo JL, Rodriguez-Rodriguez E, Soininen H, de Mendonça A, Mehrabian S, Traykov L, Hort J, Vyhnalek M, Thomassen JQ, Pijnenburg YAL, Holstege H, van Swieten J, Ramakers I, Verhey F, Scheltens P, Graff C, Papenberg G, Giedraitis V, Boland A, Deleuze JF, Nicolas G, Dufouil C, Pasquier F, Hanon O, Debette S, Grünblatt E, Popp J, Ghidoni R, Galimberti D, Arosio B, Mecocci P, Solfrizzi V, Parnetti L, Squassina A, Tremolizzo L, Borroni B, Nacmias B, Spallazzi M, Seripa D, Rainero I, Daniele A, Bossù P, Masullo C, Rossi G, Jessen F, Fernandez V, Kehoe PG, Frikke-Schmidt R, Tsolaki M, Sánchez-Juan P, Sleegers K, Ingelsson M, Haines J, Farrer L, Mayeux R, Wang LS, Sims R, DeStefano A, Schellenberg GD, Seshadri S, Amouyel P, Williams J, van der Flier W, Ramirez A, Pericak-Vance M, Andreassen OA, Van Duijn C, Hiltunen M, Ruiz A, Dupuis J, Martin E, Lambert JC, Kunkle B, Bellenguez C. X-chromosome-wide association study for Alzheimer's disease. Mol Psychiatry. 2024 Dec 04. PMID: 39633006.
Read at: PubMed - Published on 12/3/2024
Young VM, Bernal R, Baril AA, Zeynoun J, Wiedner C, Gaona C, Beiser A, Teixeira AL, Salardini A, Pase MP, Himali JJ, Seshadri S. Long Sleep Duration, Cognitive Performance, and the Moderating Role of Depression: A Cross-Sectional Analysis in the Framingham Heart Study. medRxiv. 2024 Dec 03. PMID: 39677456.
Read at: PubMed - Published on 12/1/2024
Hu YH, Meirelles O, Shiroma EJ, Satizabal CL, Seshadri S, Tracy RP, Gudnason V, Launer LJ. Peripheral risk factors and their role in biomarker-based screening for dementia in the community. Alzheimers Dement. 2024 Dec; 20(12):8556-8565. PMID: 39718159.
Read at: PubMed - Published on 11/28/2024
van Lent DM, Jacques PF, Charisis SM, Mesa HG, Satizabal C, Yuan C, Vasan RS, Seshadri S, Beiser A, Himali JJ, Jacob ME. Dietary inflammatory index scores and cognitive aging: results from the Framingham heart Study offspring cohort. medRxiv. 2024 Nov 28. PMID: 39649578.
Read at: PubMed - Published on 11/21/2024
Luckey AM, Ghosh S, Wang CP, Beiser A, Bernal R, Li Z, Mbangdadji D, Fadaee E, Snoussi H, Dediós AGV, Trevino HA, Goss M, Hillmer LJ, Bauer CE, Staffaroni AM, Stables L, Albert M, Himali JJ, Mosley TH, Forsberg L, Guðnason V, Singh B, Singh H, Schwab K, Kramer JH, Rosenberg GA, Helmer KG, Greenberg SM, Habes M, Wang DJJ, Gold BT, Lu H, Caprihan A, Fornage M, Launer LJ, Arfanakis K, Seshadri S, DeCarli C, Maillard P, Satizabal CL. Biological validation of peak-width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium. Alzheimers Dement. 2024 Dec; 20(12):8814-8824. PMID: 39569745.
Read at: PubMed - Published on 11/20/2024
de Kort FAS, Vinke EJ, van der Lelij EJ, Anblagan D, Bastin ME, Beiser A, Brodaty H, Chaturvedi N, Cheng B, Cox SR, DeCarli C, Enzinger C, Fletcher E, Frayne R, de Groot M, Huang F, Ikram MA, Jiang J, Lam BYK, Maillard P, Mayer C, McCreary CR, Mok V, Maniega SM, Petersen M, Roshchupkin G, Sachdev PS, Schmidt R, Seiler S, Seshadri S, Sudre CH, Thomalla G, Twerenbold R, Valdés Hernández M, Vernooij MW, Wardlaw JM, Wen W, Kuijf HJ, Biessels GJ, Biesbroek JM. Cerebral white matter hyperintensity volumes: Normative age- and sex-specific values from 15 population-based cohorts comprising 14,876 individuals. Neurobiol Aging. 2025 Feb; 146:38-47. PMID: 39602940.
Read at: PubMed
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