Pattern Comparison Processing Speed Test Research Articles

Patient-Reported Outcome Screens for Cognitive Dysfunction and Predicts Admissions in Cirrhosis

IntroductionHepatic encephalopathy (HE) is a frequent complication of cirrhosis, leading to preventable hospitalizations and increased mortality. Despite the availability of validated neuro-psychometric tests to diagnose HE, only 10% of clinicians regularly screen for HE due to lack of time, equipment, and trained personnel. Materials and MethodsWe studied the association between patient-reported cognitive function and the National Institutes of Health Toolbox Cognition Battery (a validated measure of HE) in patients with cirrhosis. A single-center prospective study of adult patients undergoing liver transplantation evaluation was performed from 10/2020 to 12/2021. Cognition was assessed using the National Institutes of Health Toolbox Cognition Battery and a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey. ResultsTwenty-three liver transplantation candidates were enrolled; the mean age was 56.4 (±9.7) years, 39% were female and the most common etiologies of cirrhosis were primary biliary cirrhosis/primary sclerosing cholangitis/overlap syndrome (30%), hepatitis C (22%) and alcohol-associated liver disease (22%). The mean MELD-Na was 14.9 (±6.4). The mean PROMIS Cognitive Function T-score (PROMISCF) was 49.2 (±9.6). The mean T-scores for the List Sort Working Memory test, Flanker Inhibitory Control and Attention test, and Pattern Comparison Processing Speed test were 46.4 (±9.9), 37.8 (±6.2), and 50.22 (±16.4), respectively. PROMISCF correlated with the List Sort Working Memory test (r = 0.45, P = .03). The mean hospitalization rate was 1.6 days admitted per month. On adjusted multivariate analysis, PROMISCF predicted total hospitalization days (P < .001), hospital admissions (P = .01), and hospitalization rate (P < .001). ConclusionsA brief survey can screen for HE and predict hospitalizations in patients with cirrhosis.

The Influence of Cholesterol on Resting Brain Blood Flow and Cognition in Middle-Aged Adults

Total cholesterol increases with age, with peak values observed in middle-aged adults (50-64 years old). Middle-aged adults are vulnerable to experiencing future cognitive decline, in which the concurrent reductions in resting brain blood flow with aging have been linked to cognitive impairments. PURPOSE: To determine the influence of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol on resting brain blood flow and cognition in middle-aged adults (50-64 years old). Methods: LDL and HDL cholesterol were measured in 18 healthy adults (57 ± 4 years old). Resting cerebral and hippocampal blood flow were assessed using a pseudo-continuous arterial spin labeling (pCASL) sequence from the Human Connectome Project inside a Siemens Prisma 3T MRI scanner. Cognitive function was assessed using the Hopkins Verbal Learning Test (HVLT) and the National Institute of Health (NIH) Toolbox’s Flanker Inhibitory Control and Attention Test and Pattern Comparison Processing Speed Test. The influence of cholesterol on resting brain blood flow and cognition was analyzed using Pearson correlations. Results: LDL cholesterol (123 ± 23 mg/dL) was negatively correlated with resting cerebral (70.1 ± 12.5 ml.100g−1.min−1; r = -0.78, p = 0.0001) and hippocampal (67.6 ± 13.1 ml.100g−1.min−1; r = -0.74, p = 0.0005) blood flow. There were no significant associations for HDL cholesterol (67 ± 17 mg/dL) on resting cerebral (r = -0.03, p = 0.9) nor hippocampal (r = -0.04, p = 0.9) blood flow. Among the cognitive function tests, only hippocampal-dependent memory retention from the HVLT was positively associated with HDL cholesterol (r = 0.51, p = 0.03). A follow-up analysis revealed participants with a higher resting brain blood flow presented a tendency for higher scores in the Pattern Comparison Processing Speed Test (r = 0.44, p = 0.06). CONCLUSION: LDL cholesterol, a cardiometabolic risk factor, was negatively associated with resting cerebral and hippocampal blood flow whereas the potentially cardioprotective factor HDL cholesterol was not. HDL cholesterol was positively associated with memory-related outcomes. Our results suggest cholesterol may impact resting brain blood flow and should be considered a target in preventing or delaying age-related memory loss. Further data are required to elucidate the underlying mechanisms. SIGNIFANCE: The cardiometabolic effects of cholesterol may have additional implications on cerebrovascular and brain health. NIH/NIGMS - P20 GM113125. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cognitive and Exercise Training Improves Intraindividual Variability in Cognitive Performance in Older Adults: Secondary Findings of A Randomized Controlled Trial

AbstractBackgroundIncreased intraindividual variability of cognitive performance is a marker of cognitive decline. Whether computerized cognitive training (CCT) and aerobic exercise counteracts cognitive decline by reducing intraindividual variability is unknown. We investigated the effects of CCT with or without aerobic exercise on reaction time intraindividual variability in older adults.MethodThis was a secondary analysis of an 8‐week randomized controlled trial. Older adults (aged 65‐85 years) were randomized to CCT alone (n = 41), CCT with aerobic exercise (n = 41), or an active control group (n = 42). The CCT group trained using the Fit Brains® platform 3×/week for 1 hour (plus 3×/week of home‐based training). The CCT with aerobic exercise group received 15 min of walking plus 45 min of Fit Brains® 3×/week (plus 3×/week of home‐based training). The control group received sham exercise and cognitive training (3×/week for 1 hour). We extracted reaction times from the Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test (Flanker), and Pattern Comparison Processing Speed Test (PACPS). Intraindividual variability was measured as residual intraindividual standard deviation (residual ISD) of raw reaction time latencies. Residual ISD is an unbiased measure of variability that accounts for within and between participant source of variation that could influence reaction time latencies. We also calculated reaction time intraindividual SD (raw‐score ISD) and intraindividual coefficient of variation (ICV).ResultCompared with the control group, residual ISD improved in a processing speed task (PACPS) following CCT alone (mean difference [95% confidence interval]: ‐0.147 [‐0.230 to ‐0.065], p&lt;0.001) and CCT with aerobic exercise (‐0.111 [‐0.195 to ‐0.027], p&lt;0.01). Also, for processing speed, both CCT (‐0.173 [‐0.261 to ‐0.084], p&lt;0.001) and CCT with aerobic exercise (‐0.122 [‐0.213 to ‐0.032], p&lt;0.01) showed greater reduction in raw‐score ISD compared with controls, while only CCT reduced ICV for this task (‐0.108 [‐0.176 to ‐0.040], p&lt;0.001). Inhibitory attention (Flanker) improved only after CCT with aerobic exercise (congruent = ‐0.128 [‐0.250 to ‐0.006], incongruent = ‐0.121 [‐0.237 to ‐0.005], both p&lt;0.05).ConclusionA CCT program promoted cognitive health via reductions in intraindividual variability of cognitive performance and combining it with aerobic exercise resulted in broader benefits.

The risk of sleep‐related cognitive impairment increases in middle‐age to older adulthood

AbstractBackgroundThe association between sleep quality and cognition is widely established but the role of aging in this relationship has been unclear due to inconsistent findings with heterogeneous methods and a lack of studies in wide age ranges. The current study examined how age impacts the sleep‐cognition relationship using a large‐scale dataset with adults from young adulthood to older adulthood. Furthermore, we tested non‐linear effect of age to investigate the presence of age ranges in which the association between sleep and cognition is modified.MethodSample included 711 individuals (ages 36.00‐89.83, 59.66 ± 14.91, 55.7% female) from the Human Connectome Project‐Aging (HCP‐A). Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI), and cognitive outcome measures included the NIH Toolbox fluid cognition (Dimensional change Card Sort Test, List Sorting Working Memory Test, Picture Sequence Memory Test, Pattern comparison Processing Speed Test, Flanker Inhibitory Control and Attention Test) and crystallized cognition composite scores (Oral Reading Recognition Test and Picture Vocabulary Test), the Trail Making Test (TMT) A and B, and the Rey Auditory Verbal Learning Test (RAVLT). The association between sleep quality and cognitive performance was measured using linear regression models, with sex, race, use of sleep medication, and years of education as covariates. Age moderation was tested via the interaction between sleep and age on cognition, with age as linear and non‐linear (quadratic) terms.ResultThere was a significant interaction term between the PSQI and non‐linear age term (age2) on TMT‐B (p = 0.02) and NIH Toolbox crystallized cognition (p = 0.02), indicating that the association between poor sleep quality and cognitive performance was moderated by age. Further analyses indicated that there were “critical age ranges” in which the sleep‐cognition association was more salient (ages 50‐75 for TMT‐B and 66‐70 for crystallized cognition).ConclusionThe association between sleep quality and cognitive performance may be modified by age. Individuals of the middle‐age to early older adulthood may be more vulnerable to sleep‐related cognitive impairment, indicating the clinical importance of detection and treatment of sleep disturbance in this particular age group.

21 Comparison of the NIH Toolbox Cognition Battery to Established Performance-Based Assessments in a Pediatric Cancer Setting

Objective:This study examines the clinical validity of the NIH Toolbox Cognition Battery measures in patients with oncological diagnoses and tumor predisposition syndromes, including Neurofibromatosis, Type 1 (NF1).Participants and Methods:Participants included 158 patients (61% male, 67% White) ages 3 to 25 years (M = 8.38, SD = 4.32) who underwent neuropsychological evaluation between 2019 and 2022. Patients with brain tumors (n = 50) and leukemias (n = 49) accounted for 2/3 of the sample. The remainder had solid tumors, lymphomas, or cancer predisposition syndrome. Forty-eight had a diagnosis of NF1. Performance-based measures of attention, executive functioning, and processing speed were administered as part of neuropsychological evaluations. Patients were administered between 1 to 4 NIH Toolbox Cognition measures, including Flanker Inhibitory Control and Attention Test (Flanker), Dimensional Change Card Sort Test (DCCS), Pattern Comparison Processing Speed Test (PCCS), and List Sorting Test. Parent-reported measures of attention and EF were also obtained. Z-scores were used to compare performance across measures that assessed equivalent constructs. The rates of weak performance (&gt;1 SD below the mean) using Toolbox measures were compared to rates of weak performance on traditional neuropsychological measures (e.g., Digit Span), and rates of functional impairment (e.g., parent-reported concerns, ADHD diagnosis).Results:FSIQ, Coding, and NEPSY Inhibition correlated with all 4 Toolbox measures, while Digit Span correlated with List Sorting, DCCS, and Flanker. DCCS and PCCS correlated with verbal fluency measures. NF1 patients scored lower than non-NF1 patients on Flanker, F(1,126) = 13.01, p&lt;.001 and DCCS, F(1,150) = 6.85, p = .01. Toolbox performance did not differ significantly by age group. Rates of identified weakness were relatively similar on Toolbox measures, some traditional measures, and parent-reported attention problems. In identifying those with and without weakness, the agreement between Flanker and other measures ranged from 52% (Auditory Attention) to 66% (Coding). Agreement between DCCS and traditional measures ranged from 47% (Letter Fluency) to 80% (Switching). For PCCS, concordance ranged from 45% (Semantic Fluency) to 69% (Switching). List Sorting had 80% agreement with Digit Span and Coding.List Sorting had the highest agreement with parent-reported attention problems (76%), EF problems (72%), and ADHD diagnosis (79%). There was relatively high concurrence between DCCS and ADHD diagnosis (69%) and parent-reported attention problems (60%) and EF problems (65%) and between Flanker and ADHD diagnosis (67%). PCCS had less agreement with functional outcomes, ranging from 49% for EF problems to 58% for attention problems and ADHD diagnosis. In comparison, Digit Span had 64% agreement for EF problems, 70% for attention problems, and 73% for ADHD diagnosis.Conclusions:The NIH Toolbox Cognition Battery can be used to identify neurocognitive weaknesses in pediatric oncology patients and provide clinically meaningful data. Evaluation of the Toolbox measures’ sensitivity to change over time is warranted, as monitoring the progression of cognitive late effects is particularly salient in cancer survivorship.

Effect of Peanut Paste-based Ready-to-use School Meals With and Without Milk on Fluid Cognition in Northern Ghana: A Randomized Controlled Trial

BackgroundFew studies have investigated the role of school feeding in low- and middle-income countries as a means of improving childhood cognition. Peanut/milk ready-to-use food (PM-RUF) or cowpea offers an affordable, scalable option that might improve cognition. ObjectivesTo determine whether micronutrient-fortified PM-RUF or peanut/cowpea ready-to-use food (PC-RUF) would improve fluid cognition as assessed by 4 tests from the National Institutes of Health Toolbox Cognitive Battery when compared with a micronutrient-fortified millet porridge (FP) after a year of school feeding. MethodsAn individually randomly assigned, investigator-blinded, controlled clinical trial was conducted at 6 schools in Mion District in rural northern Ghana. Eight hundred seventy-one school children aged 5–12 y were randomly assigned and allocated to receive PM-RUF (n = 282), PC-RUF (n = 292), or FP (n = 297), each providing ∼400 kcal/d. The primary outcomes were 4 fluid cognition test scores: Dimensional Change Card Sort test, Flanker Inhibitory Control and Attention test, Pattern Comparison Processing Speed test, and a modified List Sorting Working Memory test. Secondary outcomes included a composite median ranking of the 4 primary outcomes and anthropometry changes. ResultsAmong the 871 participants (median age, 8.8 y; 47% female), 795 (91%) completed endline cognitive testing. Median attendance rates exceeded 87% in all groups. PM-RUF group demonstrated better fluid cognition on the Dimensional Change Card Sort test [odds ratio (OR): 1.5; 95% CI: 1.1, 2.0; P = 0.016] and Pattern Comparison Processing Speed test (OR: 1.4; 95% CI: 1.0, 1.9; P = 0.026) than FP, whereas there were no significant differences on Flanker Inhibitory Control and Attention or List Sorting Working Memory tests. PC-RUF group demonstrated no improvement over FP on any cognitive tests. PM-RUF group had superior fluid cognition composite median rankings (OR: 1.5; 95% CI: 1.1, 2.0; P = 0.007). ConclusionsAmong rural Ghanaian children aged 5–12 y, PM-RUF compared with FP resulted in superior fluid cognition.This trial was registered at clinicaltrials.gov as NCT04349007.

Association of Cerebral Hemodynamics and Anemia on Processing Speed in Adults with Sickle Cell Disease.

Compared to healthy controls, adult patients with Sickle Cell Disease (SCD) are anemic, and therefore have higher cardiac output and Cerebral Blood Flow (CBF) to maintain brain oxygenation. They also demonstrate comparatively more cognitive deficits due to either overt strokes or silent cerebral ischemia. However, there are few correlative studies between CBF and cognitive deficits, specifically processing speed in SCD. Such studies are important to develop biomarkers of central brain processing and ischemia for diagnosis, prognosis, and evaluating the effectiveness of potential interventions. This pilot cross-sectional study tested the hypotheses that adults with SCD and elevated CBF demonstrate lower central brain processing speed than controls on average and that CBF is inversely correlated with processing speed. We conducted a pilot cross-sectional study to assess the relation-ships between CBF, central brain processing speed, and hemoglobin levels in asymptomatic adults with SCD and controls from an urban academic medical center. MRI acquisitions at 3T consisted of 2D phase-contrast quantitative arteriograms (Qflow) of the bilateral internal carotid and vertebral arteries and 3D pseudo-continuous arterial spin labeling (pCASL) of the brain. Participants were patients with SCD (hemoglobin [Hb]SS, [Hb] SBetaThal°, or [Hb]SC) aged 22-52 years of African American descent (N=7) or community controls (Hb AA) (n=3). Processing speed was assessed as an in-direct functional marker of ischemia using a recommended test from the NIH Toolbox for Assessment of Neurological and Behavioral Function, the Pattern Comparison Processing Speed Test. t-tests were used to compare means of CBF, hemoglobin, and cognition between SCD patients and healthy controls. Among SCD patients only multivariate correla-tions were used to evaluate relationships between brain perfusion in specific brain regions vs. processing speed and CBF. The significance level was set at p≤0.05. Adults with SCD reported higher CBF compared to healthy con-trols (72.15±28.90 vs. 47.23±12.30 ml/min/100g, p=0.04), and lower hemoglobin concentration (8.64±2.33 vs. 13.33±0.58, p=0.001). Heart rate in SCD patients was higher than in controls (86.29±1.37 vs. 74.00±2.10, p=0.04). Patients with SCD demonstrated lower processing speed (96.14±21.04 vs.123±13.74, p=0.02) than controls. Among adult patients with SCD, perfusion in specific regions of the brain showed an inverse relationship with processing speed, as did whole-brain CBF (p=0.0325). These findings, although from a small sample, lend a degree of validity to the claim that processing speed is slower in people with SCD than in controls and that CBF is significantly higher in SCD patients com-pared to controls. The results also lend credence to the finding that the degree of processing speed deficiencies among adults with SCD is correlated with the degree of elevated CBF, which is known to correspond with the degree of anemia associated with SCD.

Computerized Cognitive Function Does Not Correlate With Choice Reaction Time During a Hopping Task.

Cognitive performance has been shown to be associated with musculoskeletal injury risk. Cognitive assessments are often administered in controlled environments despite sport settings challenging cognition in uncontrolled, less predictable environments. Cognitive assessments should be representative of sport demands; thus, integrating motor with cognitive assessments may be more clinically relevant. Accordingly, the purpose of this research was to investigate the relationship between tablet-based cognitive tests and choice reaction time during a hopping task. Cross-sectional. A total of 20 healthy participants volunteered to participate. Participants completed 3 tablet-based cognitive assessments. Average raw response time and fully corrected scores were used for analysis. In addition, participants completed a choice reaction hopping task to capture neuromuscular-cognitive reaction time. Participants completed a forward hop over a hurdle, landing on a single limb. Light sensors were utilized for the choice reaction component to capture reaction time in seconds, cue them when to hop, and indicate the landing limb. The relationship between the tablet-based cognitive assessments and reaction time during a hopping task was examined with Pearson correlations (α = .05). The choice reaction time from the hop task had a negligible correlation (r = -.20-.07) to the fully corrected tablet-based cognitive tests. The choice reaction time from the hop task had a negligible correlation (r = .02) to the average response time of the Pattern Comparison Processing Speed Test and a low correlation (r = .34-.36) to the Dimensional Change Card Sort Test and Flanker Inhibitory Control and Attention Test. This study determined that tablet-based cognitive assessments had trivial relationships to choice reaction time during a hopping task. This research has implications as clinicians aim to evaluate and analyze cognitive performance. Although reaction time was a critical component of all the assessments in this study, an individual's performance on a tablet-based assessment does not indicate performance during a functional reaction time assessment.

Cognitive Dysfunction Worsens with Age in Patients with Sickle Cell Disease in the Modern Treatment Era

Introduction Patients with sickle cell disease (SCD) suffer from cognitive dysfunction compared to those unaffected by the disease. Such cognitive dysfunction in patients with SCD is further exacerbated by the occurrence of overt stroke or silent cerebral infarcts (SCIs). Fortunately, treatments such as hydroxyurea and red blood cell (RBC) transfusion for patients with SCD have been shown to be neuroprotective. Studies that predate guidelines recommending all patients with HbSS or HbS beta thalassemia null genotypes receive primary disease modification with hydroxyurea report that cognitive dysfunction worsens with age in patients with SCD. However, there is limited investigation into cognitive trajectories across the lifespan during the modern treatment era for patients with SCD. While neuroprotective interventions are widely recommended, we hypothesize that patients with SCD will continue to experience cognitive decline. Methods Patients >5 years of age with any genotype of SCD, excluding those receiving chronic RBC transfusions, were included in these analyses. Cognitive data, as measured by the NIH Toolbox-Cognitive Battery (NIHTB-CB) and the Wechsler Abbreviated Scale Intelligence 2nd edition (WASI-II), were combined from three prospective research studies at a single institution. A subgroup of participants had multiple timepoints of data collected. Multivariate general linear mixed-level models, accounting for multiple timepoints per participant, were used to predict each cognitive subdomain while controlling for the independent variables of age and sex. Age squared (age2) was included in models if necessary to account for a second-order polynomial fit. Significance was defined as α<0.05 and the Benjamini-Hochberg procedure was used to correct for multiple comparison. Results Data was collected from 123 participants with SCD between 2014-2022. The cohort was 45.4% male (56/123 participants). Thirty-four participants had 2 timepoints and 7 participants had 3 timepoints of cognitive data included in the analyses, for 164 total timepoints. First and last-timepoints were separated by 1-4 years for the NIHTB-CB and 1-8 years for the WASI-II tests. The average (SD, range) number of months between the first and last encounters was 31.2 (10.9, 14.2-47.7) for completion of NIHTB-CB testing and 43.9 (22.2, 14.2-89.3) for completion of WASI-II testing. Table 1 describes the cohort. The average (SD, range) hemoglobin at all timepoints was: 9.0 (1.6, 5.6-13.3). The number (percent) of participants taking hydroxyurea and the mean (SD, range) dosage for all timepoints was: 97/164 (59.1%), 380.9mg (649.4, 11.0-2000.0). Using multivariate general linear mixed-level models to predict each cognitive subdomain and composite score provided in the NIHTB-CB and WASI-II, the Flanker Inhibitory Control and Attention (age p=0.0164), Oral Reading (age p=0.0006, age2 p=0.0018), Pattern Comparison Processing Speed (age p=0.0210, age2 p=0.0206, sex p=0.0041), Crystallized Composite (age p=0.0038, age2 p=0.0063) and Total Composite (age p=0.0215, age2 p=0.0219) scores decreased with age while controlling for the effect of sex (Table 1, Figure 1). There was not a significant relationship between age and cognitive outcome measure for the Picture Vocabulary, List Sorting Working Memory, Dimensional Change Card Sorting, Picture Sequence Memory, Fluid Composite, Matrix Reasoning or Full-Scale IQ tests. Conclusion We conclude that cognitive abilities, encompassing executive function abilities (Flanker Inhibitory Control and Attention Test), non-executive function abilities (Oral Reading Test and Crystallized Composite) and processing speed (Pattern Comparison Processing Speed Test), decrease as patients with sickle cell disease age during the modern treatment era. Further analyses are required to determine the impact of age on cognitive outcomes while controlling for the presence of infarction, primary disease modification, hemoglobin and additional biologic covariates. These preliminary analyses support further investigation into the pathophysiology of SCD on both brain development and aging, and consideration of neurocognitive outcomes in the development of new therapeutics. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Improvement of Retinal Capillary Function After High-Speed Circuit Resistance Training in Healthy Older Adults.

To determine the retinal capillary function (RCF, the efficiency of blood flow transferring in the capillary network) and its relation to cognitive function in healthy older people without known cognitive impairment following an 8-week high-speed circuit resistance training program (HSCT). Eleven subjects in the HSCT group and 7 age-matched nontraining controls (CON) were recruited. The HSCT group trained 3 times per week for 8 weeks, whereas CON performed no formal training. One eye of each subject from both groups was imaged at baseline and 8-week follow-up. Retinal blood flow (RBF) was measured using a retinal function imager, and retinal capillary density (RCD, expressed as fractal dimension Dbox) was measured using optical coherence tomography angiography. RCF was defined as the ratio of RBF to RCD. Cognitive function was assessed during both visits using the NIH Toolbox Fluid Cognition Battery. RCF was 2.07 ± 0.64 nL⋅s -1 ·Dbox -1 (mean ± SD) at baseline, and significantly increased to 2.59 ± 0.54 nL⋅s -1 ·Dbox -1 after training ( P = 0.0003) in the HSCT group, reflecting an increase of 25%. The changes of RBF were not related to the changes of RCD in the HSCT group (r = -0.18, P = 0.59). There was no significant change of RCF in the CON group ( P = 0.58). In the HSCT group, the Pattern Comparison Processing Speed Test and Fluid Cognition Composite Score were significantly increased after HSCT ( P = 0.01). Furthermore, the changes in Flanker Inhibitory Control and Attention Test (FLNK) were positively correlated to increases in RCF (r = 0.77, P = 0.005). This is the first prospective study to demonstrate that the increased RCF after HSCT was related to improved cognition in cognitively normal older adults.

Dissociable language and executive control deficits and recovery in post-stroke aphasia: An exploratory observational and case series study

A growing body of evidence indicates many, but not all, individuals with post-stroke aphasia experience executive dysfunction. Relationships between language and executive function skills are often reported in the literature, but the degree of interdependence between these abilities remains largely unanswered. Therefore, in this study, we investigated the extent to which language and executive control deficits dissociated in 1) acute stroke and 2) longitudinal aphasia recovery. Twenty-three individuals admitted to Johns Hopkins Hospital with a new left hemisphere stroke completed the Western Aphasia Battery-Revised (WAB-R), several additional language measures (of naming, semantics, spontaneous speech, and oral reading), and three non-linguistic cognitive tasks from the NIH Toolbox (i.e., Pattern Comparison Processing Speed Test, Flanker Inhibitory Control and Attention Test, and Dimensional Change Card Sort Test). Two participants with aphasia (PWA) with temporoparietal lesions, one of whom (PWA1) had greater temporal but less frontal and superior parietal damage than the other (PWA2), also completed testing at subacute (three months post-onset) and early chronic (six months post-onset) time points. In aim 1, principal component analysis on the acute test data (excluding the WAB-R) revealed language and non-linguistic executive control tasks largely loaded onto separate components. Both components were significant predictors of acute aphasia severity per the WAB-R Aphasia Quotient (AQ). Crucially, executive dysfunction explained an additional 17% of the variance in AQ beyond the explanatory power of language impairments alone. In aim 2, both case patients exhibited language and executive control deficits at the acute post-stroke stage. A dissociation was observed in longitudinal recovery of these patients. By the early chronic time point, PWA1 exhibited improved (but persistent) deficits in several language domains and recovered executive control. In contrast, PWA2 demonstrated mostly recovered language but persistent executive dysfunction. Greater damage to language and attention networks in these respective patients may explain the observed behavioral patterns. These results demonstrate that language and executive control can dissociate (at least to a degree), but both contribute to early post-stroke presentation of aphasia and likely influence longitudinal aphasia recovery.

Skin carotenoid content is associated with speed of processing in cognitively normal older adults

AbstractBackgroundBrain and retinal carotenoid content have been linked to cognitive function in older adults. Although skin carotenoid is correlated with retinal content, the relationship of skin carotenoid and cognition in older adults is unknown. Measurement of skin carotenoid is non‐invasive, quick, and easy to obtain. The purpose of this study was to evaluate the relationship between skin carotenoid concentration and cognitive performance in a population of cognitively normal, older adults.MethodBaseline data from 101 cognitively normal older adults participating in a nutrition intervention study (Nutrition Interventions for Cognitive Enhancement study; NICE study) were analyzed. Skin carotenoid content was measured using pressure‐mediated reflection spectroscopy by the Veggie Meter® (Longevity Link Corporation). A comprehensive cognitive battery was conducted by a trained psychometrician. The NICE cognitive battery includes three age and education corrected cognition tests from the NIH‐Toolbox Cognition Battery – the Pattern Comparison Processing Speed, Flanker Inhibitory Control and Attention, and Dimensional Change Card Sort Tests. We tested the relationship between skin carotenoid content and corrected NIH‐Toolbox test T‐scores using ordinary least squares regression adjusted for sex and BMI. Statistical model assumptions were evaluated through residual analyses. Statistical analyses were performed using R (v. 3.6.2; R Foundation, Vienna, Austria) and statistical significance was set at p &lt; 0.05.ResultMost participants were female (80.2%) and overweight (BMI of 28.3 ± 4.5 kg/m2) with a mean age of 71.8 ± 4.9 years. Mean skin carotenoid content was 275.1 ± 81.8. Higher skin carotenoid content was correlated with faster speed of processing (Pattern Comparison Processing Speed Test: b = ‐0.21, p = 0.03), but skin carotenoids were not related to tests of attention or executive function (Flanker Inhibitory Control and Attention Test: b = 0.12, p = 0.26 and Dimensional Change Card Sort Test: b = 0.07, p = 0.47).ConclusionThe measurement of skin carotenoids may be a useful tool to identify a modifiable risk factor for Alzheimer’s Disease. These findings will be further investigated utilizing the final sample size of the NICE Study (n=200).

Executive control deficits and lesion correlates in acute left hemisphere stroke survivors with and without aphasia.

In contrast to the traditional definition of the disorder, many individuals with aphasia exhibit non-linguistic cognitive impairments, including executive control deficits. Classic lesion studies cite frontal lobe damage in executive dysfunction, but more recent lesion symptom-mapping studies in chronic aphasia present mixed results. In this study, we compared executive control abilities of acute stroke survivors with and without aphasia and investigated lesion correlates of linguistic and non-linguistic cognitive tasks. Twenty-nine participants with acute left hemisphere stroke resulting in aphasia (n = 14) or no aphasia (n = 15) completed clinical MRI and testing, including three NIH Toolbox Cognition Batteries (Pattern Comparison Processing Speed, Flanker Inhibitory Control and Attention, and Dimensional Change Card Sort Tests) and the Boston Naming Test. We compared performance between groups using Wilcoxon rank sum tests. We used Least Absolute Shrinkage and Selection Operator Regression to identify neural markers (percent regional damage, hypoperfusion within vascular territories, and total lesion volume) of executive control deficits and anomia. Group performance was comparable on the Pattern Comparison Processing Speed Test, but people with aphasia had poorer standard scores, lower accuracy, and slower response times on the Dimensional Change Card Sort Test than people without aphasia. Damage to extrasylvian regions (dorsolateral prefrontal cortex, intraparietal sulcus) was related to executive control deficits, whereas language network damage (to inferior frontal and superior and posterior middle temporal gyri) was linked to naming impairments. These results suggest people with aphasia can exhibit comorbid executive control impairments linked to damage outside classic language network areas.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11682-021-00580-y.

Peripheral Insulin Resistance Is Unrelated to Cognition in Highly Educated, Cognitively Normal Adults

ObjectivesPeripheral insulin resistance (IR) and impaired glucose metabolism increase the risk for cognitive decline. However, data looking at peripheral IR’s relationship with cognition in cognitively normal adults is limited. This study aimed to assess the relationship between peripheral IR and tests of executive function, attention, and processing speed in cognitively normal older adults using a novel IR measure. MethodsBaseline data from 81 cognitively normal older adults participating in a nutrition intervention study (Nutrition Interventions for Cognitive Enhancement study; NICE study) were analyzed. Fasting blood draws were attained, and peripheral IR was measured using Quest Diagnostics’ Cardio IQ Insulin Resistance Panel (Test Code: 36,509). The NIH Toolbox Cognition Battery was conducted by a trained psychometrician. Executive function was measured by the Flanker Inhibitory Control and Dimensional Change Card Sort tests. The Flanker test also measures attention. Processing Speed was measured by the Pattern Comparison Processing Speed test. We constructed ordinary least squares regression models to assess IR’s relationships with the individual cognitive tests, including age, education, and gender as covariates. Statistical analyses were performed using R (v. 3.6.2; R Foundation, Vienna, Austria). Statistical significance was set at p < 0.05. ResultsParticipants were 83% female and had a mean age of 72 ± 4.9 years. The mean IR score was 29.9 ± 29.83. There was no statistically significant relationships with IR and any of the cognitive tests: Flanker Inhibitory Control (β = -0.03, P = 0.12), Dimensional Change Card Sort (β = -0.03, P = 0.16), Pattern Comparison Processing Speed (β = -0.10, P = 0.15). ConclusionsThere were no statistically significant relationships between IR scores and performance on the different cognitive tests. Although the tests were not significantly correlated with IR scores, directionality of the relationships indicated trend for higher IR being related to poorer scores. Consequently, maintaining insulin sensitivity with healthy lifestyle choices may be important for healthy brain aging. Future analyses with a larger sample size will be more informative for understanding the relationship between IR and various cognitive tests at baseline and over time. Funding SourcesNational Institutes on Aging.

A - 20 Connectivity between Default Mode and Salience Networks is Associated with Decreased Attention and Inhibitory Control

Abstract Objective To determine the association of default mode (DMN) and salience (SAL) network connectivity to executive function test performance. We hypothesized that intranetwork connectivity of the DMN and SAL would be uncorrelated to executive function, whereas increased internetwork connectivity would be associated with lower executive function. Methods Twelve physically active and healthy young adults (7 females, 5 males; age: 23.41 ± 2.74 years) were recruited for this study. Participants completed resting-state functional magnetic resonance imaging and three executive function tests administered through the NIH Toolbox Cognitive Battery. Demographically-corrected T-scores were calculated from the Flanker Inhibitory Control and Attention Test (FICA), Dimensional Change Card Sort Test (DCCS), and Pattern Comparison Processing Speed Test (PCPS). The relationship between intra- and internetwork connectivity of the DMN and SAL networks and performance. Results Independently, the DMN and SAL networks demonstrated weak correlations to DCCS (SAL: r = 0.45, p = 0.14; DMN: r = 0.13, p = 0.69), FICA (SAL r = −0.10, p = 0.95; DMN: r = 0.31, p = 0.33), and PCPS (SAL r = 0.10, p = 0.79; DMN: r = 0.22, p = 0.50). However, connectivity between the SAL and DMN networks demonstrated a moderate correlation to FICA performance (r = −0.61, p = 0.02). Conclusions Greater connectivity between the DMN and SAL networks demonstrated the strongest association to attention and inhibitory control performance in physically active, young adults. This relationship suggests greater connectivity of task-negative networks to task-positive networks may interfere with ongoing processing of visuospatial attention and inhibition. Future studies should examine this relationship in athletes who sustain a head injury.

Improvement of retinal tissue perfusion after circuit resistance training in healthy older adults.

To determine the retinal tissue perfusion (RTP) and its relation to cognitive function in healthy older people after an 8-week high-speed circuit resistance training program (HSCT). Eleven subjects in the HSCT group and seven age-matched non-training controls (CON) were recruited. The HSCT group trained 3 times per week for 8weeks, while CON performed no formal training. One eye of each subject in both groups was imaged at baseline and at an 8-week follow-up, using a Retinal Function Imager to measure retinal blood flow (RBF). Retinal tissue perfusion (RTP) was calculated as RBF divided by the corresponding tissue volume. Cognitive function was assessed during both visits using the NIH Toolbox Fluid Cognition Battery. RTP was 2.99 ± 0.91nl·s-1·mm-3 (mean ± SD) at baseline and significantly increased to 3.77 ± 0.86nl·s-1·mm-3 after training (P < 0.001) in the HSCT group, reflecting an increase of 26%. In the HSCT group, the Pattern Comparison Processing Speed Test (PAT) and Fluid Cognition Composite Score (FCS) were significantly increased after HSCT (P = 0.01). Furthermore, the changes in Flanker Inhibitory Control and Attention Test (FLNK) were positively correlated to increases in RTP (r = 0.80, P = 0.003). This is the first prospective study to demonstrate that the increased RTP after HSCT was related to improved cognition in cognitively-normal elders, indicating RTP could be an imaging marker for monitoring cognitive changes due to physical activity in the elderly.

The influence of cognitive tasks on sensory organization test performance

IntroductionMany static postural tasks requiring vestibular contributions are completed while dual- tasking. ObjectiveWe investigated the influence of dual-tasks on sensory integration for postural control and cognitive performance during the sensory organization test and examined the relationship between cognitive function and dual-task cost during the sensory organization test. MethodsTwenty adults completed single and dual-task versions of the six conditions of the sensory organization test were completed during two visits separated by one week. A subset of 13 participants completed three National Institute of Health (NIH)-toolbox cognitive tests including the Flanker inhibitory control and attention test, dimensional change card sort test and pattern comparison processing speed test. Wilcoxon signed rank tests were used to compare postural sway during single and dual-task sensory organization test. Friedman’s test, with pairwise comparison post-hoc tests, was used to compare single task serial subtraction performance to the 6 dual-task sensory organization test conditions. Spearman’s correlation coefficients were used to assess the relationship between cognitive performance on NIH-toolbox test and postural and cognitive dual-task cost during the sensory organization test. ResultsPerforming a cognitive dual-task during the sensory organization test resulted in a significant increase in postural sway during condition 1 (Z=−3.26, p=0.001, ES=0.73), condition 3 (Z=−2.53, p=0.012, ES=0.56), and condition 6 (Z=−2.02, p=0.044, ES=0.45). Subtraction performance significantly decreased in during condition 6 (Z=−2.479, p=0.011, ES=0.55) compared to single-task. The dimensional change card sort test demonstrated moderate correlations with dual-task cost of serial subtraction performance in condition 5 (dimensional change card sort test: r=−0.62, p=0.02) and condition 6 (dimensional change card sort test: r=−0.56, p=0.04). Pattern comparison processing speed test scores were significantly correlated with dual-task cost of postural control during condition 2. ConclusionPerforming a cognitive task during the sensory organization test resulted in significantly increased postural sway during three conditions, particularly during visual environment manipulation oppose to vestibular and somatosensory manipulation. Cognitive performance decreased during the most complex sensory organization test condition. Additionally, we found participants with poorer executive function had greater dual-task cost during more complex sensory integration demands.

The Feasibility and Validity of Objective and Patient-Reported Measurements of Cognition During Early Critical Illness Recovery.

Cognitive outcomes are an important determinant of quality of life after critical illness, but methods to assess early cognitive impairment and cognition recovery are not established. The objective of this study was to assess the feasibility and validity of objective and patient-reported cognition assessments for generalized use during early recovery from critical illness. Patients presented from the community with acute onset of either intracerebral hemorrhage (ICH) or sepsis as representative neurologic and systemic critical illnesses. Early cognitive assessments comprised the Glasgow Coma Scale (GCS), three NIH Toolbox cognition measures (Flanker Inhibitory Control and Attention Test, List Sorting Working Memory Test and Pattern Comparison Processing Speed Test) and two Patient Reported Outcomes Measurement Information System (PROMIS) cognition measures (Cognition-General Concerns and Cognition-Abilities) performed seven days after intensive care unit discharge or at hospital discharge, whichever occurred first. We enrolled 91 patients (53 with sepsis, 38 with ICH), and after attrition principally due to deaths, cognitive assessments were attempted in 73 cases. Median [interquartile range] Sequential Organ Failure Assessment scores for patients with sepsis was 7 [3, 11]. ICH cases included 13 lobar, 21 deep and 4 infratentorial hemorrhages with a median [IQR] ICH Score 2 [1, 2]. Patient-reported outcomes were successfully obtained in 42 (58% overall, 79% of sepsis and 34% of ICH) patients but scores were anomalously favorable (median 97th percentile compared to the general adult population). Analysis of the PROMIS item bank by four blinded, board-certified academic neurointensivists revealed a strong correlation between higher severity of reported symptoms and greater situational relevance of the items (ρ = 0.72, p = 0.002 correlation with expert item assessment), indicating poor construct validity in this population. NIH Toolbox tests were obtainable in only 9 (12%) patients, all of whom were unimpaired by GCS (score 15) and completed PROMIS assessments. Median scores were 5th percentile (interquartile range [2nd, 9th] percentile) and uncorrelated with self-reported symptoms. Shorter intensive care unit length of stay was associated with successful testing in both patients with ICH and sepsis, along with lower ICH Score in patients with ICH and absence of premorbid dementia in patients with sepsis (all p < 0.05). Methods of objective and patient-reported cognitive testing that have been validated for use in patients with chronic medical and neurologic illness were infeasible or yielded invalid results among a general sample of patients in this study who were in early recovery from neurologic and systemic critical illness. Longer critical illness duration and worse neurocognitive impairments, whether chronic or acute, reduced testing feasibility.

A-226 Identifying Performance Validity Indices within the NIH Toolbox

Abstract Objective The National Institute of Health Toolbox–Cognitive Battery (NIHTB-CB) is a rigorously developed, state-of-the-art neuropsychological screening battery. However, one of its current limitations is the lack of any embedded measures of performance validity. To address this critical gap, the current project explored the relevant literature to determine which NIHTB-CB indices might be most suitable for further investigation. Data Selection A targeted literature review was conducted to explore the development of embedded indicators of performance validity within contemporary neuropsychological batteries. The most foundational and scientifically rigorous literature was gathered using targeted search terms in PsycInfo and Google Scholar. Data Synthesis This selected literature base was reviewed and compared to relevant NIHTB-CB indices. The most suitable indices within the NIHTB-CB appear to include: (1) a pattern of responding on the recognition trial for the Picture Sequence Memory Test that is inconsistent with that of individuals with known brain damage; (2) a severely impaired score on the Picture Vocabulary Test and the Oral Reading Recognition Test; (3) the frequency and length of unusual reaction time differences on the Pattern Comparison Processing Speed Test; and (4) overall performance comparisons with groups with known brain injury or illness. Conclusions Several indices within the NIHTB-CB hold great promise as performance validity indicators. Future research is needed to establish the validity of these indices using simulation and known-group designs. Establishing indicators of performance validity within the NIHTB-CB will result in more rigorous clinical research and improved clinical practice.

Carotid Endarterectomy Is Associated With Postoperative Neurocognitive Improvement in Both Symptomatic and Asymptomatic Patients

While stroke after carotid endarterectomy (CEA) is rare, magnetic resonance imaging shows that “silent” microinfarctions after surgery are much more common. These microinfarcts have been correlated with neurocognitive decline. However, there is also evidence that revascularization may improve overall cognition due to improved cerebral blood flow and elimination of embolic source. As part of a trial of remote ischemic preconditioning as a possible neuroprotective mechanism during CEA, we examined the overall impact of carotid revascularization on cognitive function. This is an interim noncomparative analysis of the cohort enrolled in an institutional randomized trial for the role of remote ischemic preconditioning for CEA (RIP-CEA, NCT02808754). All patients underwent baseline neurocognitive testing using the Montreal-Cognitive Assessment (MoCA) and National Institutes of Health Toolbox (Flanker Inhibitory Control and Attention Test, the Dimensional Change Card Sort Test, and the Pattern Comparison Processing Speed Test). These tests specifically assess executive function and processing speed. MoCA was also conducted on postoperative day 1 in the hospital. The full neurocognitive testing battery was conducted again at the 1-month follow-up in the office. Score changes from baseline were examined at the follow-up time points. Eighty patients with a mean age of 71.3 ± 7.1 years (65% male, and 30% symptomatic) were enrolled. The average baseline MoCA score was 24.7 ± 2.8 and this was similar between symptomatic and asymptomatic patients (P = .6). Forty-seven percent of patients met criteria for cognitive decline (MoCA < 26) at baseline. While MoCA scores remained unchanged immediately postoperatively, patients experienced significant improvements in MoCA scores by 1 month after CEA (average MoCA score of 26.3 and only 26% qualifying as cognitive decline; P < .001). Similarly, patients experienced significant improvements in executive function (26.4 ± 4.7 months before CEA vs 28.3 ± 2.3 1 months after CEA; P < .001) and processing speed at 1 month after CEA (31.8 ± 9.2 months before CEA vs 35.8 ± 8.4 1 months after CEA; P < .001) as assessed by the National Institutes of Health toolbox. There was no difference in the number or degree of cognitive improvement between symptomatic and asymptomatic patients. Statin use was a significant predictor of improvement on MoCA score at 1 month (OR, 3.9; P < .05). Carotid revascularization with CEA is associated with significant improvements in neurocognitive function by one month post operatively across multiple domains. Statin use may be further protective. Longer term follow-up is needed to see the magnitude and durability of these cognitive improvements. Neurocognitive improvement following CEA may justify reconsideration of the role of carotid revascularization in asymptomatic patients.