Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on RecoverY

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.

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.

Eligibility Criteria:
Inclusion Criteria:

1. Age ≥18 years
2. Admitted to the 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 ICH (based on evidence of acute parenchymal hemorrhage 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.