Brains of young adults with sickle cell look older than their actual age
Study: Poorer cognitive function accompanies older-looking brain
People with sickle cell disease (SCD) have brains that appear to be more than a decade older than their actual age.
That’s according to a recent study that also found that patients with older-looking brains had poorer cognitive function.
“Our study explains how a chronic illness … can cause cognitive problems,” Andria Ford, MD, professor at Washington University School of Medicine and the study’s first author, said in a university news story. “[SCD] could impact brain development and/or aging, which ultimately affects the mental processes involved in thinking, remembering and problem solving, among others.”
The study, “Brain Age Modeling and Cognitive Outcomes in Young Adults With and Without Sickle Cell Anemia,” was published in JAMA Network Open.
SCD is caused by the production of a faulty version of hemoglobin, the protein that carries oxygen in red blood cells, which results in them taking on a sickle-like shape. The misshaped red blood cells are prone to die prematurely and block blood flow, causing patients to develop anemia, pain crises, and other symptoms and complications.
People with SCD may also have cognitive problems, including difficulties remembering, focusing, learning, and problem-solving, which can lead to problems at school or work. Such difficulties may be seen in SCD patients even in the absence of a stroke.
Brain age and actual age
Here, researchers analyzed data from 230 young Black adults — 123 with SCD and 107 people without the disease — who underwent brain MRI scans and cognitive tests to determine whether the brains of those with SCD appeared older than their real age, and if that could be related to cognitive issues.
“We hypothesized that the downstream outcomes of … [SCD] may not only slow brain development, but also accelerate brain aging, such that [brain age gap] would be increased and could be leveraged as a biomarker for brain health and cognitive outcomes,” the researchers wrote.
Brain age was estimated using DeepBrainNet, a model trained to estimate chronological age based on MRI data from more than 14,000 healthy people gathered throughout their lives. The brain age gap for each participant was calculated by subtracting the real chronological age from the estimated brain age.
“A positive BAG indicates that the estimated brain age is older than the chronological age, while a negative BAG indicates a younger estimated age,” they wrote.
The brains of SCD patients appeared to be a median of 14.2 years older than their actual age, which was almost double the brain age gap calculated in the people in the control group (median, 7.5 years). The same tendency was observed after excluding patients with a history of stroke (median brain age gap, 12.7 vs. 7.3 years).
SCD patients also had worse performances on cognitive tests and statistical analyses indicated a higher brain age gap was associated with poorer cognitive performance.
Effect of poverty on brain age
The researchers also found that socioeconomic status was correlated with brain age. In those without SCD who experienced poverty, the mean gap between their estimated brain age and actual age was more than seven years. Moreover, analyses confirmed that in these people, the more the severe the economic deprivation was, the larger the brain age gap was and the older their brains appeared.
As part of the study, researchers are performing brain scans and cognitive tests on the same participants, three years after the initial tests, to determine if their brains aged prematurely or developed abnormally.
“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,” Ford said. “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.”
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