A groundbreaking study reveals that individuals with sickle cell disease show premature brain aging, appearing 14 years older on average, leading to significant cognitive challenges.
The research, involving over 200 participants, also highlights the impact of socioeconomic factors on brain health, showing that economic hardship correlates with accelerated brain aging.
Sickle Cell Disease on Cognitive Functions
People with sickle cell disease — a chronic condition where abnormal, sticky red blood cells clump together and block oxygen delivery to vital organs — face a higher risk of stroke and cognitive disabilities as a result. Even without a history of stroke, many individuals with this condition experience difficulties with memory, focus, learning, and problem-solving, often impacting their performance at school and work.
A team of researchers and physicians at Washington University School of Medicine in St. Louis has shed light on how sickle cell disease might affect cognitive function in patients without strokes. Their study revealed that these patients tend to have brains that appear older than their actual age. Additionally, the researchers found that individuals experiencing economic hardship — regardless of whether they have sickle cell disease — also showed signs of accelerated brain aging.
The study was published today (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.”
Study Findings on Brain Aging and Cognitive Decline
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.
Socioeconomic Status and Brain Health
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.
Longitudinal Analysis of Brain Health
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.”
Reference: “Brain Age Modeling and Cognitive Outcomes in Young Adults With and Without Sickle Cell Anemia” by Andria L. Ford, Slim Fellah, Yan Wang, Kira Unger-Levinson, Maria Hagan, Martin N. Reis, Amy Mirro, Josiah B. Lewis, Chunwei Ying, Kristin P. Guilliams, Melanie E. Fields, Hongyu An, Allison A. King and Yasheng Chen, 17 January 2025, JAMA Network Open.
DOI: 10.1001/jamanetworkopen.2024.53669
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