A National Institutes of Health-funded study published in the May 12 issue of the Journal of the American Medical Association found that, compared with a group of healthy study participants, adults with sickle cell anemia showed poorer performance on neurocognitive tests, which was associated with their disease and age.

"This study suggests that some adult patients who have sickle cell disease may develop cognitive problems, such as having difficulty organizing their thoughts, making decisions, or learning, even if they do not have severe complications, such as stroke related to sickle cell disease," Susan B. Shurin, M.D., acting director of the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health, said in a news release. "Such challenges can tremendously affect a patient's quality of life, and we need to address these concerns as part of an overall approach to effectively managing sickle cell disease."

Researchers at 12 sickle cell anemia centers across the country, including the Miller School, measured neurocognitive dysfunction in neurologically asymptomatic adults with sickle cell versus healthy control individuals. The study included a comparison of neuropsychological function and neuroimaging between December 2004 and May 2008.

The findings showed that relatively healthy adults with sickle cell anemia and without a history of neurologic injury, such as stroke, showed poorer performance on neurocognitive testing than community-matched controls, and a third had performance that was below the average range.

"This study highlights the challenges of sickle cell anemia for all patients, even those who seem otherwise healthy," said Daniel Armstrong, Ph.D., professor of pediatrics, director of the UM Sickle Cell Center and Mailman Center for Child Development, and senior author of the study. "It also points out how important it is to recognize the challenges that are likely magnified for those adults who experience multiple complications. This is a horrible disease, starting at birth, and we are thankful that so many individuals with sickle cell disease are willing to be part of studies that help us learn more so that we can find ways to help more. By studying what happens in adults, we can also change the way we think about taking care of children, so that the next generation has better outcomes."

The findings suggest poorer performance may be a result of decreased oxygen delivery to the brain, and may be partially reversible or even preventable.

"The findings were not a surprise, but a challenge to see if this subtle yet significant damage could be reversed," said Thomas Harrington, M.D., assistant professor of medicine and director of UM's adult sickle cell center. "Phase 2 of this national study is ongoing, looking at transfusion therapy as a way to increase oxygen delivery and improve brain function. Sickle cell causes recurrent episodes of excruciating pain due to loss of blood flow and oxygen to the bones. Strokes can occur early in life and risk continues throughout life, leading to severe debility. However, more subtle neurologic damage has been noted for years in many children and adults and we are now beginning to more fully understand the process and, hopefully, can intervene at an earlier stage."

Another study, this one in the American Journal of Hematology, focused on the use of the drug hydroxyurea for treatment of the disease. The 17½ year follow-up of the adult patients with sickle cell anemia found that the drug has a sustained effect of reducing pain for adults, but also has the advantage of long-term survival for patients who take the medication.

"This is a seminal paper that should serve as a reminder to the patients themselves and the physicians who care for them that this drug has important benefits," said Dr. Armstrong, who also served as the author responsible for examining the effects of hydroxyurea on the offspring of the participants.

For more than two decades, Dr. Armstrong has been part of the leadership of nearly every national clinical study of sickle cell disease, including the natural history study that defined many of the complex symptoms that occur in children (Cooperative Study of Sickle Cell Disease), as well as studies of bone marrow transplantation and use of hydroxyurea in infants. He was also the previous chair of the Congressionally-mandated NHLBI Sickle Cell Disease Advisory Committee.

The University of Miami became one of the original 10 NHLBI Comprehensive Sickle Cell Centers in 1975, and in 2008 was awarded one of 11 NHLBI-funded U54 Basic and Translational Research Programs in Sickle Cell Disease in the United States. Investigators at UM from the Departments of Pediatrics, Medicine, Neurology, and Radiology are engaged in basic, clinical, and translational research on pain, pulmonary function, sleep, brain function and neurocognitive outcomes, endothelial mechanisms, hypoxia, cardiovascular function, and quality-of-life issues.

The University of Miami Sickle Cell Center is one of the largest programs in the country, with the clinical programs led by Ofelia Alvarez, M.D., professor of pediatrics, who follows nearly 700 children at Holtz Children's Hospital, and Dr. Harrington, who follows nearly 200 adults, along with inpatients and referrals at Jackson Memorial Hospital.

This large patient population allows investigators to conduct studies at UM/Jackson, work in collaboration with other hospitals in Florida, and participate in leadership of multi-center clinical trials across the nation.

"Our clinic enrolled one of the largest number of subjects nationwide for the studies because of the willingness and enthusiasm of our patients to get involved in clinical research," said Dr. Harrington. "This has been characteristic of our patients going back to the 1980s when the late Dr. Charles Pegelow directed the program. His nationally recognized research in sickle cell was due to his great energy and the trust and courage of his patients."