Use of a Computer Based Neurocognitive Software Program in Asymptomatic Neurologically Intact Adults with Sickle Cell Disease.
Authors: Crawford Regina D. , Feliu Miriam , Edwards Christopher L. , Telen Marilyn J. 
Published: October 2019

Abstract
Abstract 1524
Poster Board I-547
Incidence of stroke in sickle cell disease (SCD) is approximately 11% under the age of 20, and 24% of patients have had a stroke by age 45. In children with SCD, 24% with no history of stroke are found to have neurocognitive deficits and silent infarcts. At least 20% of adults with SCD and no history of stroke also have an abnormal MRI, and up to 63% have either an abnormal MRI or neurocognitive dysfunction. However, formal neurocognitive testing can be difficult to obtain, especially in adults, as it is costly, time-consuming, and requires specialized expertise. An office-based screening tool would therefore be beneficial in this population. CNS Vital Signs™ (CNS-VS) is a computer-based software program designed to evaluate neurocognitive deficits based on traditional neuropsychological testing. The test reports an overall score referred to as the neurocognitive index (NCI), as well as scores based on seven domains: verbal memory, visual memory, finger tapping, symbol digit coding, Stroop test, shifting attention, and continuous performance test. The domains reflect areas of memory, psychomotor speed, reaction time, cognitive flexibility and complex attention. We conducted a pilot study in neurologically intact adults with SCD (HbSS or Sβ0 thalassemia) using CNS-VS as an office-based computer-administered tool for possible screening of patients with SCD for subtle neurocognitive impairment. SCD subjects were recruited from the Duke adult sickle cell clinic. Age, sex, and race matched controls were recruited by word of mouth. Each subject also underwent screening tests for severe depression and cognitive limitations using the mini mental status exam (MMSE) and the depression dejection score (DDS) from the Profile of Moods Survey. Patients also completed a perceived stress survey. Subjects with SCD were excluded if they had a recent hospitalization for pain within three weeks prior to enrollment, history of stroke or TIA, DDS score >40, or MMSE score <20. Controls were excluded with the same DDS/MMSE scores, history of stroke or TIA, or history of sickle trait. Thirty subjects were enrolled in this pilot study, 24 patients with SCD and 6 controls. Seventeen patients were male, 13 female, and 23 of 24 patients had HbSS. Twenty-seven subjects were right hand dominant and 3 left hand dominant, and all subjects were of African-American descent. Mean age for the controls was 43.54 yrs ± 4.24, and for the SCD group 34 yrs ± 2. The mean years of education (including primary) was 15 years for both SCD patients and controls. Mean baseline Hb and Hct values among SCD patients were 8.11 ± 0.29 g/dL and 23.97 ± 0.92 and 13.48 ±1.15 g/dL and 40.60 ± 3.11 for controls. Scores on the MMSE, DDS, and perceived stress survey were not statistically different between the controls and SCD patients. Using CNS-VS, no difference was found in scores in areas of memory, reaction time, cognitive flexibility, and complex attention between SCD patients and controls. However, psychomotor standard and percentile scores were statistically different (p=0.02) between SCD patients and controls. The symbol digit coding domain also showed statistical significance (p=0.001) between the groups for both standard and percentile scores. In SCD patients, Hb was significantly correlated with NCI standard and percentile scores (p < 0.0001). Reticulocyte count, lactate dehydrogenase level, total bilirubin, and creatinine level did not show any correlation with NCI scores. Symbol digit coding appeared to be the most sensitive of the tests, although psychomotor performance also differed significantly compared to controls. Decreased cognitive and psychomotor performance can reflect either localized or diffuse brain damage. The impact of medications, mild depression, and pain may also explain differences between the groups. Therefore, we believe that CNS Vital Signs™ is a promising screening tool for subtle neurocognitive deficits in asymptomatic neurologically intact adults with SCD. Our findings need to be validated in a larger cohort, along with correlation of scores with MRI results and expansion of testing to include patients with other variants of SCD.

Disclosures
No relevant conflicts of interest to declare.