A common type of brain bleed in older adults, known as subdural hemorrhage, is associated with the presence of amyloid deposits in cerebral blood vessels, according to a study led by researchers at Weill Cornell Medicine, NewYork-Presbyterian and Yale School of Medicine. The study is the first to link cerebral vessel amyloid to subdural hemorrhages and should lead to a better understanding of both conditions.
For the study, which appears Dec. 26 in JAMA Neurology, the researchers analyzed two large population-based cohorts covering more than 600,000 participants in the United Kingdom and United States. They found that patients with amyloid deposits in the cerebral vessels—a condition called cerebral amyloid angiopathy (CAA)—were at least five times more likely to experience subdural hemorrhages, compared with patients without CAA.
At present, clinicians generally don't consider isolated subdural hemorrhages as part of the spectrum of cerebral amyloid angiopathy. So, if this link is established, then clinicians will start to screen and evaluate subdural hemorrhage patients for underlying CAA, which would be a major paradigm shift and could lead to better care and better outcomes."
Dr. Santosh Murthy, study co-senior author, associate professor of neurology at Weill Cornell Medicine and the associate chief of the division of neurocritical care at New York-Presbyterian/Weill Cornell Medical Center
The study's other co-senior author was Dr. Guido Falcone, associate professor of neurology at Yale School of Medicine. The study's first author was Dr. Cyprien Rivier, a postdoctoral associate in the Falcone laboratory.
Subdural hemorrhages are bleeds from blood vessels that occur on the outer surface of the brain below its largest covering membrane, known as the dura. They result in trapped blood called subdural hematomas, which can put a dangerous amount of pressure on the brain, and usually require surgical removal. Subdural hemorrhages affect nearly 125,000 Americans per year, and, because of the aging population, are on their way to becoming the most common reason for brain surgery among adult patients.
CAA features amyloid beta protein aggregates in the walls of blood vessels within and just above the brain. The condition is very common in older adults—especially Alzheimer's patients, who also have amyloid deposits in other brain tissue. However, although CAA can trigger bleeding from any of the vessels where it is found, neurologists generally have considered subdural hemorrhage a separate clinical phenomenon, induced mainly by mechanical stresses on vessels due to age-related brain shrinkage.
Even so, there have been hints of a connection between the two. Roughly one-fifth of patients with CAA brain bleeds also have coexisting subdural hemorrhages, and there is some evidence that subdural hemorrhages are more common when CAA signs are more prominent on brain MRI scans. Drs. Murthy and Falcone and their colleagues therefore set up the new study as an initial investigation of this potential link.
Their analysis made use of two ongoing, long-term, population-based health studies, the UK's Biobank Program and the U.S. National Institutes of Health's All of Us Research Program, which includes data from participants enrolled by the New York City Consortium of Columbia University Irving Medical Center, Weill Cornell Medicine, NYC Health + Hospitals/Harlem and NewYork-Presbyterian. In datasets covering a total of 645,231 people, they compared the rates of subdural hemorrhages in those who did and didn't have a prior CAA diagnosis.
In the larger UK-based dataset, 3 of the 126 people with CAA and 649 of the 487,097 without CAA had a subdural hemorrhage during a median follow-up period of about 20 years. In the researchers' analysis, this implied about 7.6 times greater risk of subdural hemorrhage for the CAA group. Confirming the link, the researchers estimated about 5.2 times greater risk for CAA patients in the U.S. dataset.
The authors cautioned that while this apparent statistical linkage does not, in itself, imply that CAA causes subdural hemorrhages, it does encourage further investigation.
"The next logical step is to do a multicenter prospective study looking for the presence of amyloid using PET scans in patients who present with an isolated subdural hemorrhage," Dr. Murthy said.
Currently there are no specific treatments for CAA. It is possible that anti-amyloid therapies, which have been recently approved for use in Alzheimer's disease, will be tested in patients with CAA in the future. But in principle, Dr. Murthy added, screening subdural hemorrhage patients for CAA could uncover many patients who would benefit from such treatments when they become available.
The work described in this study was supported by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, grant number K23NS105948.
Rivier, C. A., et al. (2023). Cerebral Amyloid Angiopathy and Risk of Isolated Nontraumatic Subdural Hemorrhage. JAMA Neurology. doi.org/10.1001/jamaneurol.2023.4918.