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November 13, 2019

DISCOVERY Study Seeks to Learn More About the Causes of Post-Stroke Cognitive Impairment and Dementia

By Advancing the Science contributor

By Mass General Research Communications Staff

Stroke is the leading cause of adult disability in the US, with up to 70% of stroke survivors suffering some degree of post-stroke VCID. Furthermore, some stroke subtypes carry a disproportionate burden of the disability related to stroke.

We are excited to announce that, last month, the National Institute of Neurological Disorders and Stroke (NINDS) awarded Massachusetts General Hospital (MGH) $39M ($62+ million in total direct and indirect costs) for the DISCOVERY (Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on RecoverY) Network.

This is the largest U19 award across Partners, 3rd among largest NIH awards received by Partners, and FIRST of those received by Mass General.

Supported by the NINDS and National Institute on Aging (NIA), DISCOVERY will become a landmark study to unravel the mechanisms of post-stroke cognitive disability, early stroke recovery, and potential targets for personalized prevention, intervention and rehabilitation.

The vision of DISCOVERY is to dramatically reduce the rates of post-stroke VCID and functional disability in high-risk US populations – specifically including the health disparities populations - based on their stroke subtype or the underlying vulnerability.

"Understanding the mechanisms underlying the process of cognitive and functional recovery after stroke offers a promise of future diagnostic tools, treatment options and rehabilitation strategies that would help abate the burden of disability related to stroke," says Natalia S. Rost, MD, MPH, who is chief of the MGH Stroke Division, Professor of Neurology at Harvard Medical School and 2019-2024 Samana Cay MGH Research Scholar.

Led by Prof. Rost and Steven M. Greenberg, MD, PhD, of the MGH J. Philip Kistler Stroke Research Center, this new collaborative network consists of four novel cores and 30 premier academic clinical sites with access to acute stroke populations and the expertise and capacity for systematic assessment of post-stroke cognitive impairment and dementia.

"It takes a village to solve a problem of such complexity as post-stroke cognitive disability," says Rost. "Not only have we embarked on the greatest current challenge in the field of stroke outcomes and recovery, we are aiming to understand the mechanistic details that have never been tackled before at the depth and the scope proposed in DISCOVERY."

The complex interplay between life exposure to multiple vascular risk factorsThe DISCOVERY team will investigate the mechanisms of brain resilience and susceptibility to post-stroke VCID in a representative population of white, black and Hispanic stroke survivors in the US based on:

  • Pre-existing burden of microvascular and neurodegenerative pathology
  • The effect of strategic acute stroke lesions
  • The mediating effect of genomic/epigenomic variation

Under the leadership of the Administrative Core (Dr. Rost, MGH) and guided by the research strategy delineated by the Recruitment and Retention (Dr. James Meschia, Mayo Clinic), Statistics (Drs. Rebecca Gottesman, Johns Hopkins University and Lisa Wruck, Duke University), and Repository (Dr. Helmer, MGH) Cores, the DISCOVERY team will conduct a prospective, multi-center, observational, nested-cohort study of 8,000 nondemented ischemic and hemorrhagic stroke patients.

Study participants will be enrolled during their acute hospital admission and followed for a minimum of two years, with serial cognitive evaluations and assessments of functional post-stroke outcome. Subsets of participants will undergo research-based MRI and PET scans and comprehensive genetic/genomic and fluid biomarker testing.

"We will translate this new knowledge into practical tools for identifying patients at high risk for post-stroke VCID and propose targeted interventions for prevention, treatment, and rehabilitation of post-stroke cognitive impairment and dementia," says Rost. "Ultimately, I see a world where each patient has a chance at successful recovery after stroke."

The key scientific leadership of DISCOVERY consists of a team of recognized experts in:

Scientific ExpertiseInvestigators
Acute Stroke/Big Data ScienceNatalia Rost, MGH; Polina Golland, MIT; Jayashree Kalpathy-Cramer, MGH Martinos Center
Vascular Contributions to Impairment and DementiaSteven Greenberg, MGH; Rebecca Gottesman, JHU; Lisa Wruck, Duke; Thomas Mosley, U of Mississippi; Jennifer Manly, Columbia U
Alzheimer's DiseaseDavid Knopman, Ronald Petersen, Jonathan Graff-Radford, Mayo Clinic
Multi-Center Stroke Clinical TrialsJames Meschia, Kevin Barrett, Mayo Clinic
MRI AnalysisBruce Fischl, MGH Martinos Center; Prashanthi Vemuri, Cliff Jack Jr, Mayo Clinic
PET ImagingKeith Johnson, MGH; Val Lowe, Mayo Clinic
Hemorrhagic StrokeAlessandro Biffi, Anand Viswanathan, MGH
Genetics/GenomicsSudha Seshadri, UT-San Antonio; Myriam Fornage, UT-Houston
Fluid BiomarkersJason Hinman, UCLA; Robert Rissman, UCSD; Len Petrucelli, Mayo Clinic
Health DisparitiesBernadette Boden-Albala, UC-Irvine; Steven Kittner, U of Maryland
Large-Scale Databases/State-of-the-Art BiobankingAlex Sherman, Karl Helmer, MGH; Robert Rissman, UCSD

The proposal was developed in response to the RFA NS-19-012 (U19) ( and is jointly supported by the NINDS and NIA (U19NS115388).

This article was originally published by Mass General Research Institute, Oct. 15, 2019.


Editor's Note: At Mayo Clinic, research drives everything we do for patients, staff and caregivers. We have a unique culture of collaboration that extends beyond our walls as we seek to discover ways to improve health, and the experience of health care, for people everywhere.

The teamwork within the DISCOVERY Network is one such example that we hope will lead to better understanding of the mechanisms of post-stroke related disabilities and ways to treat, reduce or prevent them.

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Tags: aging, Clifford Jack Jr., cognitive impairment, collaboration, David Knopman, dementia, James Meschia, Jonathan Graff-Radford, Kevin Barrett, Mayo Clinic Study of Aging, neurology, News, Prashanthi Vemuri, Ronald Petersen, stroke, Val Lowe

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