Sub-Studies Overview

SUB-STUDY

LEAD

DESCRIPTION

Acute MRI

Natalia Rost, MD, MPH,

Polina Golland, PhD

This sub-study is primarily focused on comprehensive analysis of the clinical ("acute") brain MRI scans obtained at the time of admission for index stroke. The group will apply existing and develop future methodology to investigate the association between acute and chronic cerebrovascular pathology detected on the acute scans and study outcomes. Joint analyses of acute lesion volume and topography, WMH volume and overall burden of micro-vascular disease including white matter structural integrity and cerebral microbleeds, total brain and ventricular volume are some examples of the MRI characteristics to be assessed in this sub-study. This group will use already validated as well as novel machine learning approaches to the analysis of MRI scans, as well as to the acute CT and CT angiogram data available for all DISCOVERY participants.

AD/ADRD

David Knopman, MD,

Ronald Petersen, MD, PhD

This sub-study will focus their effort on analysis and thorough characterization of the DISCOVERY findings related to the neurodegenerative pathology manifestations, specifically Alzheimer disease (AD) and related dementias.

ICH/SAH/VCID

Alessandro Biffi, MD

This sub-study is focused on applying a comprehensive approach to in-depth characterization and analysis of the hemorrhagic stroke sybtypes including intracerebral and subarachnoid hemorrhage, in relation to primary outcomes in DISCOVERY. For the first time, cognitive outcomes after SAH will be systematically assessed on a large scale. Functional outcomes and neuroimaging characteristics will be used in prediction models of recovery after hemorrhagic stroke, the most deadly and disabling stroke subtype.

PET/Longitudinal

Val Lowe, MD

This sub-study will use a longitudinal design to evaluate neuro-degenerative pathology in a large subset of patients with stroke. As visualized on PET/CT scans obtained at two time-points after stroke, amyloid and tau burden analysis will provide novel insights into the role of neurodegeneration as part of the pathological cascades leading to post-stroke cognitive impairment and dementia.

Structural/Functional MRI

Prashanthi Vemuri, PhD

This sub-study is focused on acquisition, processing, and in-depth characterization of the structural and functional characteristics of the brain that are linked to brain health and resilience. Using a validated protocol, this multi-modal MRI analysis will provide important insights into brain morphometry, tissue characterization, as well as structural and functional connectivity associated with cognitive and functional post-stroke recovery in DISCOVERY.

Genetics/Genomics

Sudha Seshadri MD,

Myriam Fornage, PhD

This sub-study is focused on exhaustive analysis of genetic, genomic, and epigenomic data in DISCOVERY. A series of pre-specified analyses including whole exome genotyping, genome-wide genotyping, targeted genotyping for loci of specific interest, as well as epigenome-wide analysis of the cognitive and functional outcomes in DISCOVERY will yield novel insights into pathophysiology of stroke recovery and VCID.

Fluid Biomarkers

Jason Hinman, MD, PhD

This sub-study has developed a biomarker platform for comprehensive assessment and targeted evaluation of the underlying mechanisms of VCID after stroke. The DISCOVERY fluid biomarker strategy involves analysis of inflammatory and neuro-degenerative biomarkers, as well as biomarkers of neuro-axonal and vascular injury.