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.
- Director, Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, UT Health San Antonio
- Senior Investigator, Framingham Heart Study
- All India Institute of Medical Science (AIIMS), MD
- Christian Medical College & Hospital, MBBS
- All India Institute of Medical Science (AIIMS), DM
- Published on 6/3/2019
Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, Rutten-Jacobs L, Giese AK, van der Laan SW, Gretarsdottir S, Anderson CD, Chong M, Adams HHH, Ago T, Almgren P, Amouyel P, Ay H, Bartz TM, Benavente OR, Bevan S, Boncoraglio GB, Brown RD, Butterworth AS, Carrera C, Carty CL, Chasman DI, Chen WM, Cole JW, Correa A, Cotlarciuc I, Cruchaga C, Danesh J, de Bakker PIW, DeStefano AL, den Hoed M, Duan Q, Engelter ST, Falcone GJ, Gottesman RF, Grewal RP, Gudnason V, Gustafsson S, Haessler J, Harris TB, Hassan A, Havulinna AS, Heckbert SR, Holliday EG, Howard G, Hsu FC, Hyacinth HI, Ikram MA, Ingelsson E, Irvin MR, Jian X, Jiménez-Conde J, Johnson JA, Jukema JW, Kanai M, Keene KL, Kissela BM, Kleindorfer DO, Kooperberg C, Kubo M, Lange LA, Langefeld CD, Langenberg C, Launer LJ, Lee JM, Lemmens R, Leys D, Lewis CM, Lin WY, Lindgren AG, Lorentzen E, Magnusson PK, Maguire J, Manichaikul A, McArdle PF, Meschia JF, Mitchell BD, Mosley TH, Nalls MA, Ninomiya T, O'Donnell MJ, Psaty BM, Pulit SL, Rannikmäe K, Reiner AP, Rexrode KM, Rice K, Rich SS, Ridker PM, Rost NS, Rothwell PM, Rotter JI, Rundek T, Sacco RL, Sakaue S, Sale MM, Salomaa V, Sapkota BR, Schmidt R, Schmidt CO, Schminke U, Sharma P, Slowik A, Sudlow CLM, Tanislav C, Tatlisumak T, Taylor KD, Thijs VNS, Thorleifsson G, Thorsteinsdottir U, Tiedt S, Trompet S, Tzourio C, van Duijn CM, Walters M, Wareham NJ, Wassertheil-Smoller S, Wilson JG, Wiggins KL, Yang Q, Yusuf S, Bis JC, Pastinen T, Ruusalepp A, Schadt EE, Koplev S, Björkegren JLM, Codoni V, Civelek M, Smith NL, Trégouët DA, Christophersen IE, Roselli C, Lubitz SA, Ellinor PT, Tai ES, Kooner JS, Kato N, He J, van der Harst P, Elliott P, Chambers JC, Takeuchi F, Johnson AD, Sanghera DK, Melander O, Jern C, Strbian D, Fernandez-Cadenas I, Longstreth WT, Rolfs A, Hata J, Woo D, Rosand J, Pare G, Hopewell JC, Saleheen D, Stefansson K, Worrall BB, Kittner SJ, Seshadri S, Fornage M, Markus HS, Howson JMM, Kamatani Y, Debette S, Dichgans M. Publisher Correction: Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet. 2019 Jun 03. PMID: 31160810.
- Published on 6/2/2019
Weinstein G, Davis-Plourde K, Himali JJ, Zelber-Sagi S, Beiser AS, Seshadri S. Non-Alcoholic Fatty Liver Disease, Liver Fibrosis Score and Cognitive Function in Middle-Aged Adults: The Framingham Study. Liver Int. 2019 Jun 02. PMID: 31155826.
- Published on 5/22/2019
Carter AR, Gill D, Davies NM, Taylor AE, Tillmann T, Vaucher J, Wootton RE, Munafò MR, Hemani G, Malik R, Seshadri S, Woo D, Burgess S, Davey Smith G, Holmes MV, Tzoulaki I, Howe LD, Dehghan A. Understanding the consequences of education inequality on cardiovascular disease: mendelian randomisation study. BMJ. 2019 05 22; 365:l1855. PMID: 31122926.
- Published on 5/14/2019
Aparicio HJ, Himali JJ, Satizabal CL, Pase MP, Romero JR, Kase CS, Beiser AS, Seshadri S. Temporal Trends in Ischemic Stroke Incidence in Younger Adults in the Framingham Study. Stroke. 2019 Jun; 50(6):1558-1560. PMID: 31084341.
- Published on 5/1/2019
Davies G, Lam M, Harris SE, Trampush JW, Luciano M, Hill WD, Hagenaars SP, Ritchie SJ, Marioni RE, Fawns-Ritchie C, Liewald DCM, Okely JA, Ahola-Olli AV, Barnes CLK, Bertram L, Bis JC, Burdick KE, Christoforou A, DeRosse P, Djurovic S, Espeseth T, Giakoumaki S, Giddaluru S, Gustavson DE, Hayward C, Hofer E, Ikram MA, Karlsson R, Knowles E, Lahti J, Leber M, Li S, Mather KA, Melle I, Morris D, Oldmeadow C, Palviainen T, Payton A, Pazoki R, Petrovic K, Reynolds CA, Sargurupremraj M, Scholz M, Smith JA, Smith AV, Terzikhan N, Thalamuthu A, Trompet S, van der Lee SJ, Ware EB, Windham BG, Wright MJ, Yang J, Yu J, Ames D, Amin N, Amouyel P, Andreassen OA, Armstrong NJ, Assareh AA, Attia JR, Attix D, Avramopoulos D, Bennett DA, Böhmer AC, Boyle PA, Brodaty H, Campbell H, Cannon TD, Cirulli ET, Congdon E, Conley ED, Corley J, Cox SR, Dale AM, Dehghan A, Dick D, Dickinson D, Eriksson JG, Evangelou E, Faul JD, Ford I, Freimer NA, Gao H, Giegling I, Gillespie NA, Gordon SD, Gottesman RF, Griswold ME, Gudnason V, Harris TB, Hartmann AM, Hatzimanolis A, Heiss G, Holliday EG, Joshi PK, Kähönen M, Kardia SLR, Karlsson I, Kleineidam L, Knopman DS, Kochan NA, Konte B, Kwok JB, Le Hellard S, Lee T, Lehtimäki T, Li SC, Lill CM, Liu T, Koini M, London E, Longstreth WT, Lopez OL, Loukola A, Luck T, Lundervold AJ, Lundquist A, Lyytikäinen LP, Martin NG, Montgomery GW, Murray AD, Need AC, Noordam R, Nyberg L, Ollier W, Papenberg G, Pattie A, Polasek O, Poldrack RA, Psaty BM, Reppermund S, Riedel-Heller SG, Rose RJ, Rotter JI, Roussos P, Rovio SP, Saba Y, Sabb FW, Sachdev PS, Satizabal CL, Schmid M, Scott RJ, Scult MA, Simino J, Slagboom PE, Smyrnis N, Soumaré A, Stefanis NC, Stott DJ, Straub RE, Sundet K, Taylor AM, Taylor KD, Tzoulaki I, Tzourio C, Uitterlinden A, Vitart V, Voineskos AN, Kaprio J, Wagner M, Wagner H, Weinhold L, Wen KH, Widen E, Yang Q, Zhao W, Adams HHH, Arking DE, Bilder RM, Bitsios P, Boerwinkle E, Chiba-Falek O, Corvin A, De Jager PL, Debette S, Donohoe G, Elliott P, Fitzpatrick AL, Gill M, Glahn DC, Hägg S, Hansell NK, Hariri AR, Ikram MK, Jukema JW, Vuoksimaa E, Keller MC, Kremen WS, Launer L, Lindenberger U, Palotie A, Pedersen NL, Pendleton N, Porteous DJ, Räikkönen K, Raitakari OT, Ramirez A, Reinvang I, Rudan I, Dan Rujescu, Schmidt R, Schmidt H, Schofield PW, Schofield PR, Starr JM, Steen VM, Trollor JN, Turner ST, Van Duijn CM, Villringer A, Weinberger DR, Weir DR, Wilson JF, Malhotra A, McIntosh AM, Gale CR, Seshadri S, Mosley TH, Bressler J, Lencz T, Deary IJ. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nat Commun. 2019 May 01; 10(1):2068. PMID: 31043617.
- Published on 4/17/2019
Kivimäki M, Singh-Manoux A, Pentti J, Sabia S, Nyberg ST, Alfredsson L, Goldberg M, Knutsson A, Koskenvuo M, Koskinen A, Kouvonen A, Nordin M, Oksanen T, Strandberg T, Suominen SB, Theorell T, Vahtera J, Väänänen A, Virtanen M, Westerholm P, Westerlund H, Zins M, Seshadri S, Batty GD, Sipilä PN, Shipley MJ, Lindbohm JV, Ferrie JE, Jokela M. Physical inactivity, cardiometabolic disease, and risk of dementia: an individual-participant meta-analysis. BMJ. 2019 04 17; 365:l1495. PMID: 30995986.
- Published on 4/5/2019
Spartano NL, Davis-Plourde KL, Himali JJ, Andersson C, Pase MP, Maillard P, DeCarli C, Murabito JM, Beiser AS, Vasan RS, Seshadri S. Association of Accelerometer-Measured Light-Intensity Physical Activity With Brain Volume: The Framingham Heart Study. JAMA Netw Open. 2019 Apr 05; 2(4):e192745. PMID: 31002329.
- Published on 4/1/2019
Mishra A, Chauhan G, Violleau MH, Vojinovic D, Jian X, Bis JC, Li S, Saba Y, Grenier-Boley B, Yang Q, Bartz TM, Hofer E, Soumaré A, Peng F, Duperron MG, Foglio M, Mosley TH, Schmidt R, Psaty BM, Launer LJ, Boerwinkle E, Zhu Y, Mazoyer B, Lathrop M, Bellenguez C, Van Duijn CM, Ikram MA, Schmidt H, Longstreth WT, Fornage M, Seshadri S, Joutel A, Tzourio C, Debette S. Association of variants in HTRA1 and NOTCH3 with MRI-defined extremes of cerebral small vessel disease in older subjects. Brain. 2019 Apr 01; 142(4):1009-1023. PMID: 30859180.
- Published on 3/30/2019
Adams HHH, Roshchupkin GV, DeCarli C, Franke B, Grabe HJ, Habes M, Jahanshad N, Medland SE, Niessen W, Satizabal CL, Schmidt R, Seshadri S, Teumer A, Thompson PM, Vernooij MW, Wittfeld K, Ikram MA. Full exploitation of high dimensionality in brain imaging: The JPND working group statement and findings. Alzheimers Dement (Amst). 2019 Dec; 11:286-290. PMID: 30976649.
- Published on 3/4/2019
Pase MP, Beiser AS, Himali JJ, Satizabal CL, Aparicio HJ, DeCarli C, Chêne G, Dufouil C, Seshadri S. Assessment of Plasma Total Tau Level as a Predictive Biomarker for Dementia and Related Endophenotypes. JAMA Neurol. 2019 Mar 04. PMID: 30830207.
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