Neurocognitive Assessment of Adults with Sickle Cell Disease: A Descriptive Study
Authors: Oluwole Olubusola , Fertrin Kleber Yotsumoto , Kruse-Jarres Rebecca 
Published: November 2021

Abstract
Introduction: Sickle cell disease (SCD) causes devastating complications that can affect any organ in the body. Particularly, SCD can present with neurological complications of overt strokes, silent infarcts and cognitive impairment. As patients are living longer with SCD, cognitive functioning is an important aspect of their disease as deficits can impact education, employment, or adherence to medications. Most of the studies assessing cognitive impairment in this population have been in children with limited data on adults. This study explored the results of cognitive testing in adult patients with SCD when compared to normative data. This study also sought to determine any association between psychological factors (baseline anxiety and depression) as well as biological factors (i.e. hemoglobin levels).
Methods: This was a cross-sectional study conducted at the Sickle Cell Center of Southern Louisiana in New Orleans.The study included adults with a diagnosis of sickle cell disease regardless of subtype who were over the age of 18. Patients were excluded if they were not able to physically complete the tasks. Executive function, memory, psychomotor speed, and memory were assessed using the following tasks from standardized pencil-and-paper cognitive tasks from the Cambridge Neuropsychological Automated Battery (CANTAB) test: Stocking of Cambridge (SOC),Delayed Matching to Sample (DMS), Paired Associates Learning (PAL), Motor Screening Task (MOT), Intra-Extra Dimensional Set Shift (IED), Spatial Working Memory (SWM). The Hospital Anxiety and Depression Subscale (HADS) clinical assessment tool was used to screen for anxiety and depression at the time of testing. A HADS score &gt;8 denotes significant anxiety or depression.
Results: A total of 22 patients (59% females, mean age 29.6±2.1 years) were included in this study. Attention and psychomotor speed were relatively preserved cognitive domains with 59.1% of patients scoring greater than 75 thpercentile relative to normative mean. Conversely, executive functioning often appeared impaired with 72.7% and 77.3% of patients scoring below 25 thpercentile in outcome measures of IED and SWM, respectively. Similarly, a significant percentage of patients scored below 25 thpercentile in outcome measures of visual memory, PAL and DMS, 63.6% and 45.4%, respectively. Fifteen participants (68%) screened positive for anxiety while two screened positive for depression. Patients with anxiety tended to perform worse on most cognitive tasks, although the differences in scores did not reach statistical significance. Additional analyses of association of biologic factors and neurocognitive functioning are currently underway.
Discussion and Conclusion: Our results support that adults with sickle cell disease often suffer from cognitive deficits, which was expected based on pediatric studies demonstrating cognitive impairment in children with SCD. Interestingly, we observed a predominance of poor executive function over changes in attention and psychomotor speed in this study. This is in contrast with what providers familiar with "mini mental assessment" for dementia may expect. Typical dementia patients develop attention and memory changes before executive function is affected. Therefore, it is possible that cognitive impairment in SCD may go by unnoticed without proper testing. Additionally, in this cohort, anxiety was frequent and tended to associate with worse performance. Since this is a cross-sectional study, it is unclear whether cognition is progressively impaired over the years. Prospective studies are required to help determine whether and how fast progression occurs and what risk factors are implicated in the development and progression of cognitive impairment. Such deficits have been demonstrated to be associated with difficulties around employment and adherence to medication, which ultimately jeopardizes long term outcomes. Overall, we recommend neurocognitive and psychological evaluations as part of the routine care for adult SCD patients since abnormal findings seem common and may not be obvious without adequate testing for different domains. Treatment of anxiety disorder and cognitive rehabilitation may prove helpful to improve cognition in SCD patients.

Disclosures
Fertrin: Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kruse-Jarres: Genentech/Roche: Speakers Bureau; Pfizer: Consultancy; CSL Behring: Consultancy; CRISPR: Consultancy; Biomarin: Consultancy; Genentech: Consultancy, Research Funding.