Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited blood disease that can cause intense pain episodes and may lead to organ failure. Preliminary studies have shown that adults with SCD may have brain abnormalities that contribute to problems with cognitive functioning, including attention and memory difficulties. This study will use brain magnetic resonance imaging (MRI) and neuropsychological testing to examine the differences in cognitive functioning in adults with SCD and adults without SCD.

212 subjects participated in this cross-sectional study consisting of screening questionnaires, a neuropsychological testing battery, and MRI testing. Enrollment into this study ended in May 2008.

SCD is an inherited blood disorder. Symptoms include anemia, infections, organ damage, and intense episodes of pain, which are called "sickle cell crises." In the past, SCD was considered a fatal disease, and many people with SCD died at a young age. Due to advances in medical care, people with SCD are now living longer lives; however, they often experience a deterioration in quality of life due to progressive organ failure. Past research has suggested that children with SCD commonly have frontal lobe dysfunction syndrome, which is a brain disorder that can affect cognitive functioning in areas such as attention, concentration, information processing, and decision making. Often times, however, neurocognitive and brain disorders are not diagnosed or treated in people with SCD. In preliminary brain imaging studies, at least half of adult participants with SCD had cognitive dysfunction that could be seen in images of the brain, while participants without SCD rarely had visible changes in the brain. Brain dysfunction may be one of the most important and least-studied problems affecting adults with SCD. The purpose of this study is to evaluate the extent of cognitive functioning problems in adults with SCD. The study will also determine if there is a connection between cognitive functioning problems and abnormalities seen on MRI brain images of adults with SCD.

This study is an observational case/control study that will enroll adults with SCD and a control group of healthy adults who do not have SCD. At a study visit on Day 1, participants will undergo blood collection and will complete psychosocial questionnaires. Female participants will provide a urine sample for pregnancy testing. Study researchers will conduct a medical record review, a physical exam, and a neurological exam. They will also interview participants to collect medical history information. On Day 2, participants will undergo either a brain MRI or neuropsychological testing; on Day 3, the other procedure will be completed. On Day 4, study researchers will explain the study procedure results to participants. Participants will be asked if they are willing to take part in a second phase of the study in the future. Enrollment into this study ended in May 2008.

A pilot interventional study follows this study, and is reported separately in ClinicalTrials.gov under NCT 00850018.

Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as cases into the study:

1. Adult between the ages of 21 and 55
2. African descent
3. Proficient/fluent in English
4. Hemoglobin electrophoresis confirming hemoglobin SS or SB0 (%A <= 15)
5. Hemoglobin <= 10 g/dL
6. Capable of giving informed consent for the protocol

Individuals who meet all of the following criteria are eligible for enrollment as community controls into the study:

1. Adult between the ages of 21 and 55
2. African descent
3. Proficient/fluent in English
4. Capable of giving informed consent for the protocol

Exclusion Criteria:

Individuals who meet any of the following criteria are disqualified from enrollment in the case group of the study:

1. Overt stroke

2. Previous evidence of an abnormal MRI or CT other than small peri-ventricular or watershed lesions

3. History of head injury that resulted in neurological symptoms or medical visit

4. Abnormal neurologic exam with focal findings

5. Mini-Mental Status Examination (MMSE) score of < 20

6. Profile of Mood States (POMS) score on the Depression-Dejection Subscale suggestive of a clinical depression (score > 40)

7. Alcohol consumption exceeding 14 drinks/week if female, 21 drinks/week if male

8. Drug abuse, defined as using non-prescribed medication

9. History of claustrophobia and/or presence of metallic implants such as pacemakers, surgical aneurysm clips, or known metal fragments embedded in the body

10. Pregnancy

11. Baseline blood pressure > 140/90 on two repeated measurements. A second measurement is needed only if the first is > 140/90

12. History of uncontrolled hypertension

13. Any chronic disorder that may result in neurocognitive or brain dysfunction that is not secondary to SCD including:

    1. Inflammatory arterial disorders (lupus, polyarteritis)
    2. History of cancer requiring chemotherapy and/or radiation
    3. Untreated hyperlipidemia
    4. Diabetes
    5. Ongoing active infection such as HIV, tuberculosis, sarcoidosis
    6. History of chronic transfusion
    7. Chronic renal failure/Dialysis
    8. Chronic lung disease characterized by need for oxygen
    9. Morbid obesity (weight >115 kg)
    10. Heart disease: history of congestive heart failure, history of severe coronary artery disease characterized by angioplasty or surgery, or history of angina
    11. Active hepatitis or liver failure
    12. Acquired or congenital immune deficiency
    13. History of psychoses (delusions, hallucinations) and/or schizophrenia
    14. Neurodegenerative disorders
    15. Genetic disorder associated with neurocognitive dysfunction such as Down Syndrome
    16. Other chronic illness or disorder other than SCD that will adversely affect the subject's performance in the study

14. Currently on Procrit or related drug that stimulates red blood cell production

Individuals who meet any of the following criteria are disqualified from enrollment as community controls in to the study:

1. Hb electrophoresis other than AA

2. Abnormal Hb (females: < 12 g/dL; males: < 13.5 g/dL)

3. Overt stroke

4. Previous abnormal MRI or CT

5. History of head injury that resulted in neurological symptoms or medical visit

6. Abnormal neurologic exam with focal findings

7. Mini-Mental Status Examination (MMSE) score of < 20

8. Profile of Mood States (POMS) score on the Depression-Dejection Subscale suggestive of a clinical depression (score > 40)

9. Alcohol consumption exceeding 14 drinks/week if female, 21 drinks/week if male

10. Drug abuse, defined as using non-prescribed medication

11. History of claustrophobia and/or presence of metallic implants such as pacemakers, surgical aneurysm clips, or known metal fragments embedded in the body

12. Pregnancy

13. Baseline blood pressure > 140/90 on two repeated measurements. A second measurement is needed only if the first is > 140/90

14. History of uncontrolled hypertension

15. Any chronic disorder that may result in neurocognitive or brain dysfunction including:

    1. Inflammatory arterial disorders (lupus, polyarteritis)
    2. History of cancer requiring chemotherapy and/or radiation
    3. Untreated hyperlipidemia
    4. Diabetes
    5. Ongoing active infection such as HIV, tuberculosis, sarcoidosis
    6. History of chronic transfusion
    7. Chronic renal failure/Dialysis
    8. Chronic lung disease characterized by need for oxygen
    9. Morbid obesity (weight > 115 kg)
    10. Heart disease: history of congestive heart failure, history of severe coronary artery disease characterized by angioplasty or surgery, or history of angina
    11. Active hepatitis or liver failure
    12. Acquired or congenital immune deficiency
    13. History of psychoses (delusions, hallucinations) and/or schizophrenia
    14. Neurodegenerative disorders
    15. Genetic disorder associated with neurocognitive dysfunction such as Down Syndrome
    16. Other chronic illness or disorder that will adversely affect the subject's performance in the study

16. Currently on Procrit or related drug that stimulates red blood cell production

212 participants, 160 will have sickle cell anemia, 52 will be matched controls based on gender, age, and education level