Neurology and Neurosurgery

Aug. 25, 2022

Mayo Clinic is playing a key role in a nationwide effort to investigate susceptibility to post-stroke cognitive impairment in diverse populations. Funded by the National Institutes of Health, the multicenter Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on Recovery (DISCOVERY) clinical trial draws on Mayo Clinic's broad expertise in neurology and neuroimaging.

"About one-third of people with no history of cognitive impairment will develop dementia after having a stroke. That's a much higher risk compared with the general population," says Jonathan Graff-Radford, M.D., a neurologist at Mayo Clinic in Rochester, Minnesota, and a researcher in the Alzheimer's Disease Research Center. "That increased risk isn't completely explained by the stroke itself. Some biologic process is occurring that we don't yet understand. We hope this work helps us find that missing link."

DISCOVERY will prospectively study 8,000 individuals with no history of cognitive impairment who are hospitalized with acute-onset ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage. Blood tests, cognitive and functional assessments, and imaging will be evaluated to identify biomarkers and potential therapeutic targets.

"We are building a rich database to map out the trajectory of recovery after stroke," says Michelle P. Lin, M.D., M.P.H., a neurologist at Mayo Clinic in Jacksonville, Florida, and the study's principal investigator for that site. "DISCOVERY's sample size, detailed temporal assessments and expansive biomarker components make it a very robust study."

Led by Massachusetts General Hospital, the 30-center study is structured to include people typically underrepresented in medical research. Ensuring that diverse patients are invited to participate is the responsibility of DISCOVERY's recruitment core, which is led by James F. Meschia, M.D., a neurologist at Mayo Clinic's campus in Florida.

"Cardiovascular disease tends to have a disproportionate impact on underrepresented populations," Dr. Lin says. "We want to determine whether genetic factors or social determinants of health perhaps play a role in post-stroke cognitive impairment. The study sites were selected strategically to include diverse populations."

Aiming for personalized therapies

The complex factors underlying post-stroke cognitive impairment go well beyond stroke size.

"We know that even a small stroke in a critical brain structure can lead to significant cognitive impairment," Dr. Graff-Radford says. "Previous studies have mostly focused on specific brain regions, such as the thalamus and hippocampus. But a small lesion in a highly connected brain area could take out the hub of all those connecting areas and lead to dementia."

DISCOVERY's researchers hypothesize that:

• Preexisting indicators of brain health as well as the size, type and location of a stroke play an important role in cognitive recovery after stroke
• Certain specific stroke events occurring in individuals with underlying genetic or biological risk factors can affect cognitive abilities after stroke
• Assessing thinking and memory alongside brain imaging and blood samples allows for earlier identification of declining brain health after stroke

The long-term goal is to personalize post-stroke treatment. "Different types of strokes might require different biomarkers and different interventions," Dr. Graff-Radford says. "This study can help identify those individual pathways."

All participants will have baseline blood tests and cognitive and functional assessments. Cognitive and functional testing will be repeated at follow-up, along with advanced brain MRI scans and positron emission tomography (PET)-CT scans for selected subsets of participants.

Mayo Clinic's Aging and Dementia Imaging Research Laboratory is coordinating DISCOVERY's nationwide MRI testing. "The specialized MRI scans will provide important insights into the structural and functional characteristics of the brain that are linked to brain health and resilience," says Prashanthi Vemuri, Ph.D., an imaging scientist in the laboratory.

Other DISCOVERY substudies led by Mayo Clinic researchers will provide:

• Longitudinal analysis of amyloid and tau burden as visualized on PET-CT scans after stroke
• Analysis of the main study's findings concerning Alzheimer's disease and related dementias

"Our collaborative nature and our expertise in multiple domains — including cognitive disorders, MRI and PET imaging — are what make Mayo Clinic a great partner in this large, national study," Dr. Graff-Radford says.

For more information

Alzheimer's Disease Research Center. Mayo Clinic.

Aging and Dementia Imaging Research Laboratory. Mayo Clinic.

Refer a patient to Mayo Clinic.