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
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. Pase MP, Harrison S, Misialek JR, Kline CE, Cavuoto M, Baril AA, Yiallourou S, Bisson A, Himali D, Leng Y, Yang Q, Seshadri S, Beiser A, Gottesman RF, Redline S, Lopez O, Lutsey PL, Yaffe K, Stone KL, Purcell SM, Himali JJ. Sleep Architecture, Obstructive Sleep Apnea, and Cognitive Function in Adults. JAMA Netw Open. 2023 Jul 03; 6(7):e2325152.View Related Profiles. PMID: 37462968; PMCID: PMC10354680; DOI: 10.1001/jamanetworkopen.2023.25152;
     
  2. Cronjé HT, Liu X, Odden MC, Moseholm KF, Seshadri S, Satizabal CL, Lopez OL, Bis JC, Djoussé L, Fohner AE, Psaty BM, Tracy RP, Longstreth WT, Jensen MK, Mukamal KJ. Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study. Alzheimers Dement. 2023 Jul 01.View Related Profiles. PMID: 37392405
     
  3. Dhaynaut M, Grashow R, Normandin MD, Wu O, Marengi D, Terry DP, Sanchez JS, Weisskopf MG, Speizer FE, Taylor HA, Guehl NJ, Seshadri S, Beiser A, Daneshvar DH, Johnson K, Iverson GL, Zafonte R, El Fakhri G, Baggish AL. Tau Positron Emission Tomography and Neurocognitive Function Among Former Professional American-Style Football Players. J Neurotrauma. 2023 Aug; 40(15-16):1614-1624.View Related Profiles. PMID: 37282582; PMCID: PMC10458363; DOI: 10.1089/neu.2022.0454;
     
  4. Hindley G, Shadrin AA, van der Meer D, Parker N, Cheng W, O'Connell KS, Bahrami S, Lin A, Karadag N, Holen B, Bjella T, Deary IJ, Davies G, Hill WD, Bressler J, Seshadri S, Fan CC, Ueland T, Djurovic S, Smeland OB, Frei O, Dale AM, Andreassen OA. Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy. Nat Hum Behav. 2023 Jun 26. PMID: 37365406
     
  5. Horwitz LI, Thaweethai T, Brosnahan SB, Cicek MS, Fitzgerald ML, Goldman JD, Hess R, Hodder SL, Jacoby VL, Jordan MR, Krishnan JA, Laiyemo AO, Metz TD, Nichols L, Patzer RE, Sekar A, Singer NG, Stiles LE, Taylor BS, Ahmed S, Algren HA, Anglin K, Aponte-Soto L, Ashktorab H, Bassett IV, Bedi B, Bhadelia N, Bime C, Bind MC, Black LJ, Blomkalns AL, Brim H, Castro M, Chan J, Charney AW, Chen BK, Chen LQ, Chen P, Chestek D, Chibnik LB, Chow DC, Chu HY, Clifton RG, Collins S, Costantine MM, Cribbs SK, Deeks SG, Dickinson JD, Donohue SE, Durstenfeld MS, Emery IF, Erlandson KM, Facelli JC, Farah-Abraham R, Finn AV, Fischer MS, Flaherman VJ, Fleurimont J, Fonseca V, Gallagher EJ, Gander JC, Gennaro ML, Gibson KS, Go M, Goodman SN, Granger JP, Greenway FL, Hafner JW, Han JE, Harkins MS, Hauser KSP, Heath JR, Hernandez CR, Ho O, Hoffman MK, Hoover SE, Horowitz CR, Hsu H, Hsue PY, Hughes BL, Jagannathan P, James JA, John J, Jolley S, Judd SE, Juskowich JJ, Kanjilal DG, Karlson EW, Katz SD, Kelly JD, Kelly SW, Kim AY, Kirwan JP, Knox KS, Kumar A, Lamendola-Essel MF, Lanca M, Lee-Lannotti JK, Lefebvre RC, Levy BD, Lin JY, Logarbo BP, Logue JK, Longo MT, Luciano CA, Lutrick K, Malakooti SK, Mallett G, Maranga G, Marathe JG, Marconi VC, Marshall GD, Martin CF, Martin JN, May HT, McComsey GA, McDonald D, Mendez-Figueroa H, Miele L, Mittleman MA, Mohandas S, Mouchati C, Mullington JM, Nadkarni GN, Nahin ER, Neuman RB, Newman LT, Nguyen A, Nikolich JZ, Ofotokun I, Ogbogu PU, Palatnik A, Palomares KTS, Parimon T, Parry S, Parthasarathy S, Patterson TF, Pearman A, Peluso MJ, Pemu P, Pettker CM, Plunkett BA, Pogreba-Brown K, Poppas A, Porterfield JZ, Quigley JG, Quinn DK, Raissy H, Rebello CJ, Reddy UM, Reece R, Reeder HT, Rischard FP, Rosas JM, Rosen CJ, Rouphael NG, Rouse DJ, Ruff AM, Saint Jean C, Sandoval GJ, Santana JL, Schlater SM, Sciurba FC, Selvaggi C, Seshadri S, Sesso HD, Shah DP, Shemesh E, Sherif ZA, Shinnick DJ, Simhan HN, Singh U, Sowles A, Subbian V, Sun J, Suthar MS, Teunis LJ, Thorp JM, Ticotsky A, Tita ATN, Tragus R, Tuttle KR, Urdaneta AE, Utz PJ, VanWagoner TM, Vasey A, Vernon SD, Vidal C, Walker T, Ward HD, Warren DE, Weeks RM, Weiner SJ, Weyer JC, Wheeler JL, Whiteheart SW, Wiley Z, Williams NJ, Wisnivesky JP, Wood JC, Yee LM, Young NM, Zisis SN, Foulkes AS. Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design. PLoS One. 2023; 18(6):e0286297.View Related Profiles. PMID: 37352211; PMCID: PMC10289397; DOI: 10.1371/journal.pone.0286297;
     
  6. Bouzid H, Belk JA, Jan M, Qi Y, Sarnowski C, Wirth S, Ma L, Chrostek MR, Ahmad H, Nachun D, Yao W, Beiser A, Bick AG, Bis JC, Fornage M, Longstreth WT, Lopez OL, Natarajan P, Psaty BM, Satizabal CL, Weinstock J, Larson EB, Crane PK, Keene CD, Seshadri S, Satpathy AT, Montine TJ, Jaiswal S. Clonal hematopoiesis is associated with protection from Alzheimer's disease. Nat Med. 2023 Jul; 29(7):1662-1670.View Related Profiles. PMID: 37322115; PMCID: PMC10353941; DOI: 10.1038/s41591-023-02397-2;
     
  7. Horimoto ARVR, Boyken LA, Blue EE, Grinde KE, Nafikov RA, Sohi HK, Nato AQ, Bis JC, Brusco LI, Morelli L, Ramirez A, Dalmasso MC, Temple S, Satizabal C, Browning SR, Seshadri S, Wijsman EM, Thornton TA. Admixture mapping implicates 13q33.3 as ancestry-of-origin locus for Alzheimer disease in Hispanic and Latino populations. HGG Adv. 2023 Jul 13; 4(3):100207.View Related Profiles. PMID: 37333771; PMCID: PMC10276158; DOI: 10.1016/j.xhgg.2023.100207;
     
  8. 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. Alzheimers Dement. 2023 May 09. PMID: 37158312
     
  9. Scollard P, Choi SE, Lee ML, Mukherjee S, Trittschuh EH, Sanders RE, Gibbons LE, Joshi P, Devine S, Au R, Dams-O'Connor K, Saykin AJ, Seshadri S, Beiser A, Aparicio HJ, Salinas J, Gonzales MM, Pase MP, Ghosh S, Finney R, Mez J, Crane PK. Ceiling effects and differential measurement precision across calibrated cognitive scores in the Framingham Study. Neuropsychology. 2023 May; 37(4):383-397.View Related Profiles. PMID: 37276135; PMCID: PMC10247160; DOI: 10.1037/neu0000828;
     
  10. Levine DA, Chen B, Galecki AT, Gross AL, Briceño EM, Whitney RT, Ploutz-Snyder RJ, Giordani BJ, Sussman JB, Burke JF, Lazar RM, Howard VJ, Aparicio HJ, Beiser AS, Elkind MSV, Gottesman RF, Koton S, Pendlebury ST, Sharma A, Springer MV, Seshadri S, Romero JR, Hayward RA. Associations Between Vascular Risk Factor Levels and Cognitive Decline Among Stroke Survivors. JAMA Netw Open. 2023 May 01; 6(5):e2313879.View Related Profiles. PMID: 37195662; PMCID: PMC10193182; DOI: 10.1001/jamanetworkopen.2023.13879;
     
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