mechanism that may result in transient or chronic decrease in cerebral vascular reserve is likely a catalyst for CNS injury, including cognitive impairment. This can occur with transient episodes of oxygen desaturation, acute worsening anemia, or CNS vascular flow abnormalities. Obstructive sleep apnea and nocturnal hypoxemia are common treatable causes of neurocognitive injury in the general population, including patients with SCD. The rate of nocturnal hypoxemia increases following a stroke and worsens cognitive function. Screening and intervention with continuous positive airway pressure or oxygen therapy should be considered. Neuroimaging findings including stroke, silent infarction, and volume loss predict neurocognitive dysfunction and likely accelerate neurocognitive decline over time. These are risk factors for early dementia. Global cognitive impairment and executive function loss are associated with white matter damage and infarctions that are often associated with cerebrovascular disease. Gray matter loss (including atrophy of hippocampal areas) accelerates memory loss, including verbal and visual recall. Gray matter damage occurs in cerebrovascular disease, but can occur independently from chronic pain, inflammation, and intermittent hypoxia.10 Nontraumatic subdural hematoma secondary to sickling may be detected. Neuroimaging evaluation should include magnetic resonance angiography because intracranial and extracranial cerebral vascular disease, including stenosis, aneurysms, and moyamoya, is common. In addition to anatomical imaging, cerebral metabolic and flow studies are predictors for limited cerebral oxygen reserve.20,21 Increased cerebral blood flow detected from perfusion studies and transcranial Doppler are risk factors for neurologic injury in both adults and children. Unfortunately, transcranial Doppler studies in adults have not yet been validated. Cerebral oxygenation and oxygen extraction can be detected by multiple techniques. Increased oxygen extraction determined by MRI perfusion studies may become an important screening test for high risk adults. There are several laboratory risk factors for cerebral infarction, intracranial hemorrhage, and neurologic decline that largely overlap. Genetic studies have uncovered several candidate genes that increase stroke risk; however, these laboratory findings have not yet been used in clinical care. Low steady-state hemoglobin with hemolysis is central to neurologic injury. Anemia significantly correlates to lower oxygenation and poorer neurocognitive performance in SCD and in the aging general population. Anemia accelerates age-related neurocognitive decline. Hemoglobin is likely a surrogate marker for 436 American Society of Hematology reduced oxygen delivery to the brain, and the accompanying chronic nitric oxide deficiency stimulates the development of vasculopathy. Initially, anemia-induced neurocognitive impairment and cerebral oxygen desaturation may be reversible. Both transfusion and administration of hydroxyurea may improve cerebral blood flow, oxygenation, and neurocognitive function. In the general population, oxygen administration in anemic and healthy individuals improves cognitive performance. These observations suggest some of the cognitive difficulties in SCD may be due to reversible hypoxic dysfunction. There are no standard screening recommendations to detect neurocognitive or neurologic injury in the neurologically asymptomatic adult. Several diseases are accompanied by neurocognitive problems and early screening interventions are increasingly being recommended. It seems reasonable to undergo neurocognitive testing and MRI scans as patients transition to adult care. Early detection of neurologic dysfunction will allow recommendations before difficulties emerge and enable the anticipation of the functional decline in time that occurs in CNS injury. There are multiple challenges to screening neurologically asymptomatic adults. These challenges include insurance coverage, consensus agreement on the optimal test to use for screening adults, and evidence-based treatment of those adults with abnormalities. However, encouraging data suggest that hydroxyurea therapy results in meaningful improvement in cognitive function.22 In addition, cognitive remediation, educational accommodations in college, and aid in organizational and time management skills will benefit young adults as they age. Evolving neuroimaging studies and abbreviated neurocognitive screening measures for adults are undergoing study, and changes in recommendations may occur. The treatment of stroke in adults with SCD is largely expert consensusbased and summarized in recent excellent reviews.8,11,13,23,24 Exchange transfusion rather than simple transfusion is the preferred initial treatment. Preliminary data suggest chronic automated exchange transfusions may be more efficacious than standard transfusions. Thrombolytic therapy could be considered in adults, but its risks and benefits are unknown.25 Because SCD patients may have an increased rate of intracranial hemorrhage, thrombolytic therapy use in ischemic stroke should be determined by a multidisciplinary team on a case-bycase basis. Evidence-based guidelines for hemorrhagic stroke in SCD are lacking. Transfusions are often