Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on RecoverY (DISCOVERY)

The overall goal of the DISCOVERY study is to better understand what factors contribute to changes in cognitive (i.e., thinking and memory) abilities in patients who experienced a stroke. The purpose of the study is to help doctors identify patients at risk for dementia (decline in memory, thinking and other mental abilities that significantly affects daily functioning) after their stroke so that future treatments may be developed to improve outcomes in stroke patients. For this study, a "stroke" is defined as either (1) an acute ischemic stroke (AIS, or blood clot in the brain), (2) an intracerebral hemorrhage (ICH, or bleeding in the brain), (3) or an aneurysmal subarachnoid hemorrhage (aSAH, or bleeding around the brain caused by an abnormal bulge in a blood vessel that bursts).

The investigators hypothesize that:

1. The size, type and location of the stroke play an important role in recovery of thinking and memory abilities after stroke, and pre-existing indicators of brain health further determine the extent of this recovery.
2. Specific stroke events occurring in individuals with underlying genetic or biological risk factors can cause further declines in brain heath, leading to changes in thinking and memory abilities after stroke.
3. Studying thinking and memory alongside brain imaging and blood samples in patients who have had a stroke allows for earlier identification of declining brain health and development of individualized treatment plans to improve patient outcomes in the future.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; Mild Cognitive Impairment; Subarachnoid Hemorrhage; Dementia, Vascular; Intracerebral Hemorrhage; Vascular Cognitive Impairment

Detailed Description

This is a prospective, multi-center, observational, nested-cohort study. A total of 8,000 patients hospitalized at the DISCOVERY clinical sites with acute-onset AIS, ICH or aSAH and no history of dementia will be enrolled.

All participants will undergo baseline screening for evidence of pre-stroke dementia. Those who pass baseline screening will complete a blood draw and a series of cognitive and functional assessments at baseline.

Participants will undergo in-person (3-6 months, 18 months) and telephone (annual) follow-up visits for the duration of the study to assess for longitudinal cognitive and functional outcomes. In addition to Tier 1 procedures, at each in-person follow-up visit, Tier 2 participants will also undergo brain MRI scanning, comprehensive cognitive assessment batteries and longitudinal blood collection; and Tier 3 participants will also complete a specialized imaging of the brain (amyloid- and tau-PET/CT scans), which is intended to identify special biomarkers of dementia.

• Study Type: Observational
• Enrollment (Estimated): 8000

Contacts and Locations

• Study Contact: Name: James Meschia, MD; Phone Number: 904-953-6515; Email: meschia.james@mayo.edu

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Recruiting
      • Barrow Neurological Institute
      • Contact: Supreet Kaur, MD; Email: supreet.kaur@DignityHealth.org
      • Principal Investigator: Supreet Kaur, MD
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars Sinai Medical Center
      • Contact: Shlee Song, MD
      • Principal Investigator: Shlee Song, MD
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Kaiser Permanente Los Angeles Medical Center
      • Principal Investigator: Navdeep Sangha, MD
      • Contact: Navdeep Sangha, MD
      • Contact: Pamela Cheng, DO
      • Principal Investigator: Pamela Cheng, DO
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California Los Angeles
      • Contact: Katherine Mun, MD
      • Principal Investigator: Katherine Mun, MD
    • San Diego, California, United States, 92037
      • Recruiting
      • University of California San Diego
      • Contact: Brett Meyer, MD
      • Principal Investigator: Brett Meyer, MD
  • Colorado
    • Denver, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
      • Contact: Jennifer Simpson, MD
      • Principal Investigator: Jennifer Simpson, MD
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic
      • Contact: Michelle Lin, MD, MPH
      • Principal Investigator: Michelle Lin, MD, MPH
    • Miami, Florida, United States, 33125
      • Recruiting
      • University of Miami Health System
      • Contact: Nicole Sur, MD
      • Principal Investigator: Nicole Sur, MD
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago Medical Center
      • Contact: Karen Orjuela, MD, MS
      • Principal Investigator: Karen Orjuela, MD, MS
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University
      • Contact: Jason Mackey, MD
      • Principal Investigator: Jason Mackey, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Active, not recruiting
      • University of Iowa
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland Medical Center
      • Contact: Gunjan Parikh, MD
      • Principal Investigator: Gunjan Parikh, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Natalia Rost, MD
      • Principal Investigator: Natalia Rost, MD
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Boston Medical Center
      • Contact: Hugo Aparicio, MD, MPH
      • Principal Investigator: Hugo Aparicio, MD, MPH
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Active, not recruiting
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota Health
      • Contact: Kamakshi Lakshminarayan, MD, PhD, MS
      • Principal Investigator: Kamakshi Lakshminarayan, MD, PhD, MS
    • Rochester, Minnesota, United States, 55902
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Eugene Scharf, MD
      • Contact: Eugene Scharf, MD
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Recruiting
      • University of Mississippi Medical Center
      • Contact: Shreyas Gangadhara, MD
      • Principal Investigator: Shreyas Gangadhara, MD
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Contact: Michael Waters, MD, PhD
      • Principal Investigator: Michael Waters, MD, PhD
    • The Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
      • Contact: Daniel Antoniello, MD
      • Principal Investigator: Daniel Antoniello, MD
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Recruiting
      • Duke University Medical Center
      • Contact: Nada El Husseini, MD, MHS
      • Principal Investigator: Nada El Husseini, MD, MHS
    • Winston-Salem, North Carolina, United States, 27157
      • Active, not recruiting
      • Wake Forest Baptist Health
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati
      • Contact: Stacie Demel, DO, PhD
      • Principal Investigator: Stacie Demel, DO, PhD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • The Hospital of the University of Pennsylvania
      • Contact: Kelly Sloane, MD
      • Principal Investigator: Kelly Sloane, MD
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Recruiting
      • Methodist University Hospital
      • Principal Investigator: Balaji Krishnaiah, MD
      • Contact: Balaji Krishnaiah, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Research Institute
      • Contact: Rajan Gadhia, MD
      • Principal Investigator: Rajan Gadhia, MD
    • Houston, Texas, United States, 77030
      • Recruiting
      • UTHealth
      • Principal Investigator: Sean Savitz, MD
      • Contact: Sean Savitz, MD
      • Contact: Seema Aggarwal, PhD, APRN, AGNP-C
      • Principal Investigator: Seema Aggarwal, PhD, APRN, AGNP-C
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • University of Texas Health Science Center at San Antonio
      • Contact: Andrew Slusher, MD
      • Principal Investigator: Andrew Slusher, MD
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah
      • Contact: Jennifer Majersik, MD, MS
      • Principal Investigator: Jennifer Majersik, MD, MS
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia
      • Contact: Bradford Worrall, MD
      • Principal Investigator: Bradford Worrall, MD
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • University of Washington, Harborview Medical Center
      • Contact: Rizwan Kalani, MD
      • Principal Investigator: Rizwan Kalani, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with recent (≤ 6 weeks) acute ischemic stroke, intracerebral hemorrhage or aneurysmal subarachnoid hemorrhage and no history of dementia.

Description

Inclusion Criteria:

1. Age ≥18 years
2. Admitted to the enrolling clinical performance site (CPS) hospital with a diagnosis of acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), or aneurysmal subarachnoid hemorrhage (aSAH)
3. Radiographic confirmatory evidence of: (1) AIS (based on a focal area of restricted diffusion on MRI), (2) non-traumatic primary ICH (based on evidence of acute parenchymal hemorrhage on CT or brain MRI) or (3) non-traumatic acute aSAH (based on evidence of subarachnoid hemorrhage on CT or MRI and evidence of aneurysm on CT angiography, MR angiography, or conventional catheter-based angiography)
4. Able to complete baseline visit in person or by phone within 6 weeks of stroke onset
5. Able to provide informed consent by self or proxy
6. Fluent in English or Spanish prior to stroke onset

Exclusion Criteria:

1. Documented history of pre-stroke dementia or fails dementia pre-screen
2. Concurrently enrolled into a study that is not approved under the DISCOVERY Co-Enrollment Policy

3. Unable to complete study protocol (advanced directives such as comfort measures only, or inability to complete the study due to severe medical/behavioral co-morbidities), as determined by physician investigator during screening process

   Additional exclusion criteria for Tier 2 participants:

4. Contraindication to MRI: presence of electrically, magnetically, or mechanically activated implants (such as cardiac pacemakers, cochlear implants, implanted pumps); or metallic clips in the brain

   Additional exclusion criteria for Tier 3 participants:

5. Age <50 years
6. Biologically female individuals who are pregnant or seeking to become pregnant
7. Known to have one of the following genetic conditions which can increase the risk of developing cancer: Cowden disease, Lynch syndrome, hypogammaglobulinemia, Wiskott-Aldrich syndrome, Down's syndrome.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in post-stroke cognitive impairment and dementia (PSCID) diagnosis status	Baseline to 48 months post-index stroke

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in cognitive function	Baseline to 3-6, 12, 18, 24, 36 and 48 months post-index stroke

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Natalia Rost, MD, MPH, Massachusetts General Hospital; Principal Investigator: Steven Greenberg, MD, PhD, Massachusetts General Hospital

Publications and helpful links

Helpful Links

• Official Website for the DISCOVERY Study

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: May 13, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 7, 2021

Study Record Updates

• Last Update Posted (Estimated): November 3, 2025
• Last Update Submitted That Met QC Criteria: October 31, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Pathologic Processes; Neurocognitive Disorders; Hemorrhage; Cognition Disorders; Dementia; Arteriosclerosis; Arterial Occlusive Diseases; Leukoencephalopathies; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Intracranial Hemorrhages; Stroke; Pathological Conditions, Signs and Symptoms; Ischemic Stroke; Cognitive Dysfunction; Dementia, Vascular; Cerebral Hemorrhage; Subarachnoid Hemorrhage
• Other Study ID Numbers: 2020P001099; U19NS115388 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Contingent upon approval from the DISCOVERY Project Steering Committee and Sharing Subcommittee, or the NINDS (upon completion of the study), data, imaging and/or samples from consenting participants may be shared with other external researchers for future research. All identifiers and study-specific codes will be removed and assigned a second randomized identifier. The key linking each identifier to a study-specific code will be in the possession of the DISCOVERY Repository Core and will not be shared with external researchers.

Upon completion of the study, the study database will be available to NINDS along with a data dictionary and all information needed to utilize the data in future research in accordance with the informed consent. De-identified genetic information derived from this study will be deposited in the US NIH genomic database (dbGAP and future iterations) and used for future research.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No