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Brains of people with sickle cell disease appear older

Study also finds socioeconomic status linked to brain health in adults

by Marta WegorzewskaJanuary 17, 2025

brain imagesYasheng Chen

Individuals with sickle cell disease – a chronic illness where misshapen, sticky blood cells clump together, reducing oxygen delivery to organs – are at a higher risk for stroke and resulting cognitive disability. But even in the absence of stroke, many such patients struggle with remembering, focusing, learning and problem solving, among other cognitive problems, with many facing challenges in school and in the workplace.

Now a multidisciplinary team of researchers and physicians at Washington University School of Medicine in St. Louis has published a study that helps explain how the illness might affect cognitive performance in sickle cell patients without a history of stroke. The researchers found such participants had brains that appeared older than expected for their age. Individuals experiencing economic deprivation, who struggle to meet basic needs, even in the absence of sickle cell disease, had more-aged appearing brains, the team also found.

The study was published January 17 in JAMA Network Open.

“Our study explains how a chronic illness and low socioeconomic status can cause cognitive problems,” said Andria Ford, MD, a professor of neurology and chief of the section of stroke and cerebrovascular diseases at WashU Medicine and corresponding author on the study. “We found that such factors could impact brain development and/or aging, which ultimately affects the mental processes involved in thinking, remembering and problem solving, among others. Understanding the influence that sickle cell disease and economic deprivation have on brain structure may lead to treatments and preventive measures that potentially could preserve cognitive function.”

More than 200 young, Black adults with and without sickle cell disease, living in St. Louis and the surrounding region in eastern Missouri and southwestern Illinois, participated in brain MRI scans and cognitive tests. The researchers – including Yasheng Chen, DSc, an associate professor of neurology at WashU Medicine and senior author on the study – calculated each person’s brain age using a brain-age prediction tool that was developed using MRI brain scans from a diverse group of more than 14,000 healthy people of known ages. The estimated brain age was compared with the individual’s actual age.

The researchers found that participants with sickle cell disease had brains that appeared an average of 14 years older than their actual age. Sickle cell participants with older-looking brains also scored lower on cognitive tests.

The study also found that socioeconomic status correlates with brain age. On average, a seven-year gap was found between the brain age and the participants’ actual age in healthy individuals experiencing poverty. The more severe the economic deprivation, the older the brains of such study subjects appeared.

Healthy brains shrink as people age, while premature shrinking is characteristic of neurological illnesses such as Alzheimer’s disease. But a smaller brain that appears older can also result from stunted growth early in life. Sickle cell disease is congenital, chronically depriving the developing brain of oxygen and possibly affecting its growth from birth. Also, children exposed to long-term economic deprivation and poverty experience cognitive challenges that affect their academic performance, Ford explained.

As a part of the same study, the researchers are again performing cognitive tests and scanning the brains of the same healthy and sickle cell participants three years after their first scan to investigate if the older-looking brains aged prematurely, or if their development was stunted.

“A single brain scan helps measure the participants’ brain age only in that moment,” said Ford, who treats patients at Barnes-Jewish Hospital. “But multiple time points can help us understand if the brain is stable, initially capturing differences that were present since childhood, or prematurely aging and able to predict the trajectory of someone’s cognitive decline. Identifying who is at greatest risk for future cognitive disability with a single MRI scan can be a powerful tool for helping patients with neurological conditions.”

Ford AL, Fellah S, Wang Y, Unger- Levinson K1, Hagan M, Reis MN, Mirro A, Lewis JB, Ying C, Guilliams KP, Fields ME, An H, King AA, Yasheng C. Brain age modelling and cognitive outcomes in young adults with and without sickle cell anemia. JAMA Network Open. January 17, 2025.

This study was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH), grant number 5KL2TR002346; the National Institute of Neurological Disorders and Stroke of the NIH, grant numbers K23NS099472 and RF1NS116565; and the National Heart, Lung, and Blood Institute of the NIH, grant numbers K23HL136904, R01HL157188 and R01HL129241. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Melanie E. Fields has equity ownership in Proclara Biosciences and receives compensation from Global Blood Therapeutics and Pfizer Inc. for consultant services. Hongyu An receives compensation from Pfizer Inc. for consultant services.

About Washington University School of Medicine

WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,900 faculty. Its National Institutes of Health (NIH) research funding portfolio is the second largest among U.S. medical schools and has grown 56% in the last seven years. Together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,900 faculty physicians practicing at 130 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.

Marta covers pathology & immunology, pediatrics, obstetrics & gynecology, anesthesiology, ophthalmology and technology management, among other topics. She holds a bachelor’s degree in biology from Georgetown University and a PhD in immunology from the University of California, San Francisco. She did her postdoctoral work in Washington University’s Department of Pathology & Immunology. Marta joined WashU Medicine Marketing & Communications in 2023 after working as a science writer in the Department of Biology on the Danforth Campus for five years.