Correlation Between VOC and Cognitive Function Using the NIH ToolBox in SCD
Authors: de Acha Olivia Perez , Coring Terrell , Rahman Iris , Quasie-woode Devona , Chou Jilling , Smith Hedy , Hardy Steven J 
Published: June 2024

Abstract

Presentation Date: 6/9/2024
Presentation Start Time: 4:00:00 PM

Background
Frequency of vaso-occlusive crises (VOCs) is a known predictor of mortality as well as organ complications in patients with sickle cell disease (SCD) (1-3). Increasingly studied are the neurocognitive complications in adults with SCD. The most common presentation of such is a decline in executive function, described mainly in the pediatric SCD population (4,5) and which occurs independent of MRI changes on brain imaging (6,7). The NIH toolbox is a battery of cognitive tests, and multidimensional set of measures assessing cognitive, emotional, motor, and sensory function that have been shown to correlate with cognitive decline in various populations originally developed within the NIH Blueprint for Neuroscience Research and validated for ages 3-85.
In this study, we hypothesize that there will be lower neurocognition scores in SCD patients at baseline when compared to healthy individuals and that it would correlate negatively with number of VOC using the NIH tests.

Methods
This is a prospective observational study being conducted at MedStar Washington Hospital Center with planned followed up for the next months. This study was given IRB approval from MHRI. We recruited patients with SCD with VOC as inclusion criteria, and then after written informed consent, assessed them cognitively at baseline, and at 6 month-increments with planned followed up for a total of 36 months. During each visit we applied the Cognitive NIH Toolbox to assess their cognitive function in six domains (executive function, attention, episodic memory, language, processing speed, and working memory). We recorded the patients scores in each domain at baseline and in 6-month intervals. Scores were compared to national average cognition scores and adjusted for age. There were also tests that we computed the raw score (Oral symbol and auditory verbal tests). We recorded the number of VOC the patient had experienced up until the scheduled incremental visit. Herein, we will present the baseline data assessments from 27 patients, analyzed using Kendall’s rank correlation estimate, and 95% CI from 1000 bootstraps replicates.

Results
27 patients with SCD were analyzed: 74% were Hb SS (20/27), followed by 18% of HbSC (5/27) and 7% of HbS/β Thalassemia (2/27). The average age was 23.5 years old (range 21-39). Female to Male ratio was 1:1. The average number of VOC was 3.3 during the first period of 6 month follow up. Strikingly, compared to the national average, more than 50% of SCD patients scored below than the national average on all tests, and most prominently on the Flanker Inhibitory Control with 100% of patients scoring below. Likewise, in the following tests SCD patients scored below national average when compared to age matched controls respectively: List Sorting Working Memory and Dimensional Change Card Sort (80%), Pattern Comparison Processing test (70.37%), Picture Sequence (77.78%), Auditory Verbal Learning (59.26%), and lastly in the Oral Symbol Digit test (52.18%). Of the 7 battery tests, the Pattern Comparison Processing Speed Test, correlated the best with poor neurocognition and number of VOC using Kendall rank tau number of -0.459 (CI 95% -0.718, -0.143). In Fig 1, we represent the scatter plots of all 7 tests and their correlation with VOC.

Conclusions
We know that decreased cognitive functioning in SCD, whether associated with overt stroke, silent cerebral infarcts, or depression associated with chronic pain, can negatively impact SCD patients. However, we lack an objective tool to assess such changes in an otherwise younger highfunctioning population - of SCD patients, where dementia testing, for instance the MoCa test, can miss subtle progressive decline. Using the NIH toolbox cognitive battery of tests, our preliminary results show that SCD patients have lower scores in all domains of the battery of tests when compared to age-matched normal controls from a national database implying that they have subtle neurocognition deficits. The Pattern Comparison test is the most sensitive test for identifying these differences, with our data showing that patients with &gt;3 vaso-occlusive events in the year before the study having lower scores than their counterparts with &lt; 3 VOC, using this testing modality (Fig 1A).
To our knowledge, we are the first to validate a test for non-pediatric SCD patients that negatively correlates neurocognitive decline with the number of VOC.
NIH Toolbox scores: National average scores comparison to SCD scores