Predictors Of Cognitive Outcomes Research Articles

Utility of Baseline Pathological, Neuroimaging and Clinical Markers for Progression Prognosis and Subtype Classification in Early Parkinson’s Disease: Implications for Cognitive Impairment

AbstractBackgroundCognitive dysfunction is a well‐recognised PD symptom, but it is highly heterogenous and under‐assessed clinically. Interestingly, PD motor subtypes are associated with different risk of cognitive decline. However, subtype classification is currently reliant on subjective clinician assessment and may consequently be misdiagnosed. Therefore, objective biomarkers of PD progression are critically needed, but must be validated prior to clinical deployment. We assessed the utility of various clinical, neuroimaging and pathological measures as predictors of cognitive outcomes up to 5‐years follow‐up in early PD.MethodData was extracted from the Parkinson’s Progression Markers Initiative. Cognitive assessments were compiled into an overall cognition score via principal component analysis. Distinct subgroups were identified via Fuzzy C‐Means clustering on Year‐5 Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores. Models predicting cluster membership were created via logistic regression and a stratified cross‐validation machine learning pipeline, comparing two predictor inputs: 1) baseline motor assessments; and 2) incorporating additional measures, including prodromal assessments (sleep, olfactory and autonomic function), neuroimaging (proxy SN volume, striatal DaT binding) and biofluid markers (CSF alpha‐syn, p‐tau, a‐beta, and serum IGF‐1) at baseline. Finally, cluster membership was used for retroactive assessment of baseline and follow‐up cognitive data.ResultsTwo clusters were identified, with cluster two (n = 117) demonstrating higher rigidity, lower DaT binding, worsened motor outcomes and increased mood dysfunction at follow‐up compared to tremor‐dominant cluster one (n = 183). Additionally, rigid‐dominant membership was predicted by male sex, higher p‐tau, along with lower a‐beta, predicting 40% of variance (n = 111). This was significantly higher (P<0.001) than baseline motor scores alone, only accounting for 18% of variance. This was supported by machine learning, whereby incorporating additional assessments corresponded to a classification accuracy of 62%, compared to 26% when omitted. Finally, higher probability of belonging to the rigid‐dominant cluster yielded significant negative correlations cognition at baseline and follow‐up.ConclusionIncreased likelihood of rigid‐dominance corresponded to more profound cognitive decline, which may in part result from neuropathological marker concentrations as highlighted by predictive models. Therefore, further tracking of this cohort, specifically conversion into MCI or dementia, could provide insight into pathological contribution to differences in cognitive decline between PD subtypes.

Not all regions are created equal: identifying regions and cell types associated with cognitive resilience in the AD‐BXD model population

AbstractBackgroundThe relationship between regional cell composition, brain pathology, and memory impairment in Alzheimer’s disease (AD) remains incompletely understood. The specific brain regions and tracts (and their interactions) that explain the heterogeneity of cognitive decline with AD are not clear. By integrating brain‐wide immunohistochemistry and cognitive outcomes we can achieve unbiased detection of regions of interest (ROIs) and identify cellular correlates of cognitive resilience for causal testing.MethodImmunohistochemistry(IHC) was completed to evaluate neurodegeneration (NeuN), gliosis (Iba1&GFAP), amyloid beta(Aβ) pathology(AB1‐42), and cell bodies(Thionine) in adult (6 months(m)) and middle‐aged (14m) mice of the AD‐BXD genetic reference panel (n = 227). Using the QUINT workflow, hemibrain slices were systematically segmented and registered to the Allen Brain Atlas to gain a global perspective of percent cell and pathology coverage. IHC traits were correlated with contextual fear conditioning outcomes to identify regions whose stain composition is associated with memory performance.ResultsContrary to our prior work using ELISA‐based Aβ measurement, we find that Aβ quantified via IHC at the presymptomatic time point (6m) is strongly correlated with differences in short‐ and long‐term memory in 14m female 5XFAD carriers. Furthermore, the degree of astrogliosis at 6m in cortical, striatal, and thalamic regions acts as a predictor of cognitive outcomes at 14m. While age‐related decreases in NeuN load were not observed, wide variation in neurodegeneration levels could be attributed to strain differences and 14m NeuN load was positively correlated with 14m long‐term memory among this female 5XFAD population. Highlighting the importance of genetic background on AD progression, we were able to categorize strains as resilient or susceptible to pathological and cognitive decline and evaluate the overlap of these traits. Strains that exhibit the unique identity of being pathologically susceptible but cognitively resilient offer a novel opportunity to investigate the underlying mechanisms of protection from cognitive decline with AD.ConclusionIntegrating brain‐wide IHC and behavioral data, we were able to identify regional and cellular correlates that may predict downstream cognitive outcomes. Detection of these biomarkers may prove a valuable resource to disseminate the insidious prodromal stages of AD in which biochemical changes precede apparent clinical symptoms.

Brain Volumes and Cognition in Patients with Sickle Cell Anaemia: A Systematic Review and Meta-Analysis.

Cognitive decline is a major problem in paediatric and adult patients with sickle cell anaemia (SCA) and affects the quality of life. Multiple studies investigating the association between quantitative and qualitative neuroimaging findings and cognition have had mixed results. Hence, the aetiology of cognitive decline in this population is not clearly understood. Several studies have established cerebral atrophy in SCA children as well as adults, but the relationship between cognition and brain volumes remains unclear. The purpose of this systematic review was therefore to evaluate the literature on regional brain volumes and their association with cognitive outcomes. We also meta-analysed studies which compared regional brain volumes between patients and controls. Studies report that patients with SCA tend to have lower grey matter volumes, including total subcortical volumes in childhood as compared to controls, which stabilise in young adulthood and may be subjected to decline with age in older adulthood. White matter volumes remain stable in children but are subjected to reduced volumes in young adulthood. Age and haemoglobin are better predictors of cognitive outcomes as compared to regional brain volumes.

Social determinants of cognitive outcomes in survivors of pediatric brain tumors treated with conformal radiation therapy.

Social determinants of health including parental occupation, household income, and neighborhood environment are predictors of cognitive outcomes among healthy and ill children; however, few pediatric oncology studies have investigated this relationship. This study utilized the Economic Hardship Index (EHI) to measure neighborhood-level social and economic conditions to predict cognitive outcomes among children treated for brain tumors (BT) with conformal radiation therapy (RT). Two hundred and forty-one children treated on a prospective, longitudinal, phase II trial of conformal photon RT (54-59.4 Gy) for ependymoma, low-grade glioma, or craniopharyngioma (52% female, 79% white, age at RT = 7.76 ± 4.98 years) completed serial cognitive assessments (intelligence quotient [IQ], reading, math, and adaptive functioning) for ten years. Six US census tract-level EHI scores were calculated for an overall EHI score: unemployment, dependency, education, income, crowded housing, and poverty. Established socioeconomic status (SES) measures from the extant literature were also derived. Correlations and non-parametric tests revealed EHI variables share modest variance with other SES measures. Income, unemployment, and poverty overlapped most with individual SES measures. Linear mixed models, accounting for sex, age at RT, and tumor location, revealed EHI variables predicted all cognitive variables at baseline and change in IQ and math over time, with EHI overall and poverty most consistent predictors. Higher economic hardship was associated with lower cognitive scores. Neighborhood-level measures of socioeconomic conditions can help inform understanding of long-term cognitive and academic outcomes in survivors of pediatric BT. Future investigation of poverty's driving forces and the impact of economic hardship on children with other catastrophic diseases is needed.

Longitudinal Cognitive Outcomes in Children With HIV in Zambia: 2-Year Outcomes From the HIV-Associated Neurocognitive Disorders in Zambia (HANDZ) Study.

To describe longitudinal outcomes and predictors of cognitive outcomes in children with HIV in Zambia. Multiple studies have shown that children with HIV are at risk for impaired cognition. However, there are limited data on longitudinal cognitive outcomes in children with HIV. We conducted a prospective cohort study of 208 perinatally infected children with HIV ages 8-17 years, all treated with antiretroviral therapy, and 208 HIV-exposed uninfected controls. Participants were followed for 2 years. Cognition was assessed with a custom NIH Toolbox Cognition Battery, and tests were combined to generate a Summary Cognition Score (SCS). The contribution of potential risk factors to outcomes was explored using regression models and group-based trajectory modeling. HIV was strongly associated with lower SCS at baseline [β-14, 95% confidence interval (CI): -20 to -7, P < 0.001]. Change scores over time were similar between groups, but poorer average performance in children with HIV persisted at the 2-year follow-up visit (adjusted β = -11, 95% CI: -22 to -0.3, P = 0.04). Other than HIV, the strongest predictors of baseline SCS included socioeconomic status index (β =3, 95% CI: 1, 5, P = 0.004), history of growth stunting (β=-14, 95% CI: -23 to -6, P = 0.001), history of CD4 count below 200 (β = -19, 95% CI: -35 to -2, P = 0.02), and history of World Health Organization stage 4 disease (β = -10, 95% CI: -19 to -0.2, P = 0.04). In the group-based trajectory model, HIV+ status predicted membership in the lowest performing trajectory group (odds ratio 2.5, 95% CI: 1.2 to 5.1, P = 0.01). Children with HIV are at risk of poor cognitive outcomes, despite chronic treatment with antiretroviral therapy.

Nucleus basalis of Meynert predicts cognition after deep brain stimulation in Parkinson's disease

IntroductionSubthalamic DBS in Parkinson's disease has been associated with cognitive decline in few cases. Volume reduction of the nucleus basalis of Meynert (NBM) seems to precede cognitive impairment in Parkinson's disease. In this retrospective study, we evaluated NBM volume as a predictor of cognitive outcome 1 year after subthalamic DBS. MethodsNBM volumes were calculated from preoperative MRIs using voxel-based morphometry. Cognitive outcome was defined as the relative change of MMSE or DemTect scores from pre-to 1 year postoperatively. A multiple linear regression analysis adjusted for the number of cognitive domains affected in the preoperative neuropsychological testing and UPDRS III was conducted. To account for other variables and potential non-linear effects, an additional machine learning analysis using random forests was applied. Results55 patients with Parkinson's disease (39 male, age 61.4 ± 7.5 years, disease duration 10.8 ± 4.7 years) who received bilateral subthalamic DBS electrodes at our center were included. Although overall cognition did not change significantly, individual change in cognitive abilities was variable. Cognitive outcome could be predicted based on NBM size (B = 208.98, p = 0.022*) in the regression model (F(3,49) = 2.869; R2 of 0.149; p = 0.046*). Using random forests with more variables, cognitive outcome could also be predicted (average root mean squared error between predicted and true cognitive change 11.28 ± 9.51, p = 0.039*). Also in this model, NBM volume was the most predictive variable. ConclusionNBM volume can be used as a simple non-invasive predictor for cognitive outcome after DBS in Parkinson's disease, especially when combined with other clinical parameters that are prognostically relevant.

Neonatal Isoflurane Does Not Affect Sleep Architecture and Minimally Alters Neuronal Beta Oscillations in Adolescent Rats.

General anesthetics are neurotoxic to the developing rodent and primate brains leading to neurocognitive and socio-affective impairment later in life. In addition, sleep patterns are important predictors of cognitive outcomes. Yet, little is known about how anesthetics affect sleep-wake behaviors and their corresponding oscillations. Here we examine how neonatal general anesthesia affects sleep and wake behavior and associated neuronal oscillations. We exposed male and female rat pups to either 6 h of continuous isoflurane or sham anesthesia (compressed air) at the peak of their brain development (postnatal day 7). One cohort of animals was used to examine neurotoxic insult 2 h post-anesthesia exposure. At weaning age, a second cohort of rats was implanted with cortical electroencephalogram electrodes and allowed to recover. During adolescence, we measured sleep architecture (divided into wake, non-rapid eye movement, and rapid eye movement sleep) and electroencephalogram power spectra over a 24 h period. We found that exposure to neonatal isoflurane caused extensive neurotoxicity but did not disrupt sleep architecture in adolescent rats. However, these animals had a small but significant reduction in beta oscillations, specifically in the 12–20 Hz beta 1 range, associated with wake behavior. Furthermore, beta oscillations play a critical role in cortical development, cognitive processing, and homeostatic sleep drive. We speculate that dysregulation of beta oscillations may be implicated in cognitive and socio-affective outcomes associated with neonatal anesthesia.

Effects of Cognitive Reserve on Cognition in Individuals With Central Nervous System Disease.

Cognitive reserve (CR) has been proposed to account for functional outcome differences in brain pathology and its clinical manifestations. The purpose of our paper is to systematically review the effects of CR on cognitive outcomes in individuals with neurodegenerative and structural CNS diseases. We performed a systematic search of PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and PsychInfo using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Seventeen studies met the predetermined inclusion criteria and were selected for review. Education level was the most commonly used measure for CR, and various neuropsychological tests were used to measure cognitive outcomes. Regardless of the CNS disease of the individuals, almost all of the studies reported a positive association between CR and cognitive outcomes when they were evaluated cross-sectionally. However, when evaluated longitudinally, CR had either no effect on, or a negative association with, cognitive outcomes. Based on studies across a broad spectrum of CNS diseases, our findings suggest that CR may serve as a predictor of cognitive outcomes in individuals with CNS diseases. However, studies to date are limited by a lack of imaging analyses and standardized assessment strategies. The ability to use a standardized measure to assess the longitudinal effects of CR may allow for the development of more targeted treatment methods, resulting in improved disease outcomes for individuals.

Diffusion models reveal white matter microstructural changes with ageing, pathology and cognition.

White matter microstructure undergoes progressive changes during the lifespan, but the neurobiological underpinnings related to ageing and disease remains unclear. We used an advanced diffusion MRI, Neurite Orientation Dispersion and Density Imaging, to investigate the microstructural alterations due to demographics, common age-related pathological processes (amyloid, tau and white matter hyperintensities) and cognition. We also compared Neurite Orientation Dispersion and Density Imaging findings to the older Diffusion Tensor Imaging model-based findings. Three hundred and twenty-eight participants (264 cognitively unimpaired, 57 mild cognitive impairment and 7 dementia with a mean age of 68.3 ± 13.1 years) from the Mayo Clinic Study of Aging with multi-shell diffusion imaging, fluid attenuated inversion recovery MRI as well as amyloid and tau PET scans were included in this study. White matter tract level diffusion measures were calculated from Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging. Pearson correlation and multiple linear regression analyses were performed with diffusion measures as the outcome and age, sex, education/occupation, white matter hyperintensities, amyloid and tau as predictors. Analyses were also performed with each diffusion MRI measure as a predictor of cognitive outcomes. Age and white matter hyperintensities were the strongest predictors of all white matter diffusion measures with low associations with amyloid and tau. However, neurite density decrease from Neurite Orientation Dispersion and Density Imaging was observed with amyloidosis specifically in the temporal lobes. White matter integrity (mean diffusivity and free water) in the corpus callosum showed the greatest associations with cognitive measures. All diffusion measures provided information about white matter ageing and white matter changes due to age-related pathological processes and were associated with cognition. Neurite orientation dispersion and density imaging and diffusion tensor imaging are two different diffusion models that provide distinct information about variation in white matter microstructural integrity. Neurite Orientation Dispersion and Density Imaging provides additional information about synaptic density, organization and free water content which may aid in providing mechanistic insights into disease progression.

Severity of Ongoing Post-Concussive Symptoms as a Predictor of Cognitive Performance Following a Pediatric Mild Traumatic Brain Injury.

This study aimed to examine the predictors of cognitive performance in patients with pediatric mild traumatic brain injury (pmTBI) and to determine whether group differences in cognitive performance on a computerized test battery could be observed between pmTBI patients and healthy controls (HC) in the sub-acute (SA) and the early chronic (EC) phases of injury. 203 pmTBI patients recruited from emergency settings and 159 age- and sex-matched HC aged 8-18 rated their ongoing post-concussive symptoms (PCS) on the Post-Concussion Symptom Inventory and completed the Cogstate brief battery in the SA (1-11 days) phase of injury. A subset (156 pmTBI patients; 144 HC) completed testing in the EC (~4 months) phase. Within the SA phase, a group difference was only observed for the visual learning task (One-Card Learning), with pmTBI patients being less accurate relative to HC. Follow-up analyses indicated higher ongoing PCS and higher 5P clinical risk scores were significant predictors of lower One-Card Learning accuracy within SA phase, while premorbid variables (estimates of intellectual functioning, parental education, and presence of learning disabilities or attention-deficit/hyperactivity disorder) were not. The absence of group differences at EC phase is supportive of cognitive recovery by 4 months post-injury. While the severity of ongoing PCS and the 5P score were better overall predictors of cognitive performance on the Cogstate at SA relative to premorbid variables, the full regression model explained only 4.1% of the variance, highlighting the need for future work on predictors of cognitive outcomes.

A-036 Deficit Accumulation Frailty Index as a Predictor of Cognitive Outcomes in HIV+ and HIV- Adults

Abstract Objective Adults aging with HIV face elevated rates of frailty than the general aging population and are frail at younger ages, but associations between frailty and cognition in HIV are not well understood. The study aimed to examine: 1) relationships between frailty index and age, and whether relationships differed by HIV status; 2) relationships between frailty index and cognitive performance, and whether relationships differed by HIV-status. It was hypothesized that 1) the frailty index would significantly predict age in non-infected (HIV-) controls but not HIV-infected (HIV+) adults; 2) higher frailty index scores would significantly predict worse cognitive functioning regardless of HIV-status. Method Participants included 109 (39.4% HIV+) participants aged ≥45 from a community-based sample in Los Angeles. HIV-status groups did not differ by age, education, or race (p’s &amp;gt; .10). Frailty was assessed using a deficit accumulation frailty index (DAFI) composed of 32 age-related health variables. A comprehensive neurocognitive battery was used to examine motor, processing speed, executive functioning, verbal fluency, learning, memory, and global functioning. Multivariate linear regression was used to assess relationships between the DAFI and age and cognitive performance, and HIV-by-frailty interaction. Results DAFI scores were higher in HIV+ adults compared to HIV- controls. The DAFI significantly predicted global, motor, and memory performance (p’s &amp;lt; .05), but the effect was only observed in HIV- controls. The DAFI did not significantly predict age in either group. Conclusions Findings highlight that relationships between frailty and cognition may be complicated in patients with chronic health conditions. Frailty may not predict cognitive dysfunction in aging HIV+ adults.

Magnetic resonance imaging markers reflect cognitive outcome after rehabilitation in children with acquired brain injury

PurposeTo test markers from conventional and diffusion Magnetic Resonance Imaging (MRI) as possible predictors of cognitive outcome following rehabilitation therapy in children with acquired brain injury (ABI). MethodsTwenty-one children (10 boys, mean age 11.6 years, range 7.1–19.4) with stroke or traumatic brain injury underwent MRI including Diffusion Tensor Imaging (DTI) before admission to the rehabilitation centre. The conventional images were scored according to a standardised injury scoring system, and mean Fractional Anisotropy (FA) was determined within the Corpus Callosum (CC), as this structure is hypothesised to play an important role in cognition. Both conventional MRI injury scores and mean FA of the CC and its sub-regions were compared with standard functional cognitive outcome scores. Relationships between MRI indices and cognitive outcome scores were assessed using multiple regression and receiver operating characteristic (ROC) analyses. ResultsA backwards regression analysis revealed that the mean FA of the CC body and genu and the supratentorial injury score appear to represent the best predictors of outcome, together with the age at rehabilitation and time in rehabilitation. In the ROC analysis, the mean FA values of the CC body and genu and the infratentorial injury score provided the highest sensitivity, while the mean FA of the CC splenium showed the highest specificity for outcome. ConclusionsThe conventional MRI injury scores and DTI metrics from the CC reflect cognitive outcomes following rehabilitation. Neuroimaging methods such as MRI with DTI may therefore provide important markers for cognitive recovery after brain injury.

Vascular risk factors as independent predictors of neurocognitive impairments in patients with late-onset epilepsy who have small-vessel disease

RationaleLate-onset epilepsy is often accompanied by underlying cerebrovascular disease and has been associated with neurocognitive deficits even dementia, but the interrelation between them remains unknown. In this study, we aimed to explore the contribution of vascular-related and epilepsy-related factors on neurocognitive outcomes in a sample of late-onset epilepsy with history of cerebral small vessel disease. MethodsIn this retrospective cross-sectional study, a comprehensive neurocognitive assessment was performed in 25 patients aged >60 years with one or more unprovoked seizures and history of small-vessel disease. Raw scores of cognitive tests were transformed in T-scores and were grouped in 6 cognitive domains. Regression models were performed to explore the contribution of vascular risk factors (diabetes mellitus, arterial hypertension, dyslipidemia, and smoking habit) and epilepsy-related factors (drug-resistance, number of antiepileptic drugs, age at epilepsy onset, and epileptic focus localization). ResultsDiabetes (p = 0.03) and smoking habit (p = 0.05) were the best independent factors to predict attention performance; diabetes also predicted visual memory function (p = 0.02); gender was related to verbal memory performance (p = 0.04) and speed processing (p = 0.02). Age at onset predicted that executive function (p = 0.05); age (p = 0.01) and gender (p = 0.03) were the major contributors to language performance. Epilepsy-related variables did not predict any cognitive outcomes. ConclusionsVascular risk factors and sociodemographic characteristics were the best predictors of cognitive outcomes in a sample of late-onset epilepsy with cerebral small-vessel disease. Epilepsy did not show influence on cognitive function. Longitudinal studies are necessary to clarify the relationship between vascular risk factors and epilepsy on progression of cognitive deterioration in patients with late-onset epilepsy.This article is part of the Special Issue “Seizures & Stroke”

Exploring the effects of emotional design and emotional intelligence in multimedia-based learning: an engineering educational perspective

ABSTRACTEmotions are an important aspect in learning and with the current boom in instructional technology, researchers are exploring methods to investigate how emotions may be manipulated to positively influence online learning. One such method is by adapting the theory of emotional design through multimedia elements. This theory emphasises on individuality and metacognition in exploring these learning outcomes and by this we choose to explore the effects of emotional intelligence (EI). We replicated the methodology used in previous research studies in emotional design in multimedia learning by further exploring the gaps from those studies especially the effects of negative design, EI and a new sample that primarily focusses on engineering undergraduates in Malaysia. This study was designed as a quantitative quasi-experimental using a 3 × 2 factorial design. Based on the findings, it was found that emotional design is a better predictor of cognitive outcomes, whereas EI was a better predictor of emotional outcomes such as motivation and satisfaction for multimedia-based learning. It was also found that positive and negative designs have similar effects on students’ learning outcomes, while EI affected perceived satisfaction in each design.

P76. Axial impairment and EEG slowing are independent predictors of cognitive outcome in a three-year cohort of PD patients

Introduction Quantitative EEG and motor assessment tools are among the techniques investigated as biomarkers of dementia in Parkinson’s disease (PD) ( Aarsland et al., 2017 ). It is assumed that a combination of various markers has a better predictive capacity of dementia than a single technique. We aimed to check if items of Unified Parkinson’s Disease Rating Scale (UPDRS-III), related to axial symptoms, and EEG power spectra predict cognitive outcome in a three-years-cohort of patients with Parkinson’s disease. Methods We analyzed a group of patients with PD without dementia (n = 47, males 60%) at baseline and after 3 years. On inclusion: median age 66 [47, 80] years. At both time-points, the patients underwent a comprehensive neuropsychological assessment (14 cognitive tests) and neurological examination with UPDRS-III, EEG with 214 active electrodes were recorded in eyes-closed resting-state condition. The results of cognitive tests were scaled to a normative database ( Berres et al., 2000 ) and averaged to obtain an ‘overall cognitive score’ (OCS). To assess the changes over time, reliable change index (RCI) of OCS was calculated according to ( Jacobson and Truax, 1991 ). Global relative median power (GRMP) in the frequency range theta 4–8 Hz was calculated, and logarithmic transformed. A sum of UPDRS-III items: speech, rigidity (neck and all limbs), postural stability and gait, was calculated as ‘score of axial impairment’ (SAI), as mentioned in Bejjani et al., 2000 . To investigate the influence of age, sex, GRMP theta, SAI, education, and disease duration on changes of cognition we used general linear regression models with RCI as dependent variable. We checked if baseline parameters correlate between each other with Spearman rank correlation test. Results Only GRMP theta and SAI significantly predicted RCI. Combination (sum) of these two parameters improved the significance of the model. No significant correlation between these two parameters was identified. Conclusion The assessment of axial signs in combination with quantitative EEG may improve early identification of PD patients prone to severe cognitive decline. These parameters do not correlate between each other, probably covering different information aspects in the process of assessment. Larger cohorts with longer observation and various assessment tools are warranted.

BS03. EEG peculiarities and auditory long latency evoked potentials in correlation with cognitive outcome in traumatic coma patients

Introduction the aim of this study is to investigate EEG peculiarities as the possible predictors of cognitive outcome in traumatic coma patients. Methods Totally 108 traumatic coma patients investigated. Patterns of EEG background activity detected by 16 channels EEG. Auditory long latency evoked potentials (ALLEP) were studied by 16 channel EEG with regime for evoked potentials. Consciousness rated by Glasgow Coma Scale (GCS). Vegetative state (VS) and minimally conscious state (MCS) diagnosed according to international criteria. Coma recovered patients accessed by Disability Rating Scale (DRS). Cognitive status evaluated by Mini Mental Examination Scale (MMSE). Brain conventional CT or MRI (1.5 T) was done in all patients. Statistical analysis performed by SPSS 11.0. Results At first month 41 coma patients (GCS = 4–7) with alpha and delta EEG patterns died, 34 patients (GCS = 5–8) with beta (32.4%), delta (23.5%) and theta (44.1%) coma developed VS. Among them 27 patients detected to have MCS and 7 patients showed ALLEP (GCS = 4–8) with theta EEG. Another 25 (GCS = 5–8) patients with beta (28%), theta (54%) and delta (18%) background EEG recovered with different DRS (2–14) and MMSE (14–20). Positive correlation established between MCS patients with high amplitude frontal and temporal lobe theta frequencies and ALLEP (P-300) (r = +0.47; p Conclusion According to the present study the high amplitude theta background EEG with positive ALLEP is significant for favorable cognitive outcome in traumatic coma patients.

Fibrinogen concentrations predict long‐term cognitive outcome in young ischemic stroke patients

Unlabelled Box BackgroundCognitive impairment is frequent after stroke, and young patients may live with this consequence for a long time. Predictors of cognitive outcomes after stroke represent a current gap of knowledge. ObjectivesTo investigate levels of three hemostatic biomarkers as predictors of long‐term cognitive function after stroke. MethodsThis longitudinal study included consecutively recruited patients with ischemic stroke at 18‐69 years (n = 268). Blood was collected 3 months after index stroke and analyzed for plasma concentrations of fibrinogen, von Willebrand factor (VWF) and tissue‐type plasminogen activator (t‐PA) antigen. Cognitive function 7 years after index stroke was assessed by the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS). Participants with stroke <50 years of age were also examined by the Trail Making Test A and B (n = 41). Associations between biomarker concentrations and cognitive scales were assessed in the whole group and in participants with stroke <50 years of age. ResultsThe hemostatic biomarkers fibrinogen, VWF and t‐PA, were all correlated to total BNIS score, but these associations did not withstand adjustment for confounding factors in the whole group. However, in patients <50 years, we found an independent association between fibrinogen concentrations and total BNIS score (βstd = −.27, 95% confidence interval [CI], −0.47 to −0.07) and to performance on the Trail Making Test A (βstd = .31, 95% CI, 0.03–0.58). No such association was seen for the Trail Making Test B. ConclusionHigh convalescent fibrinogen concentrations were associated with worse long‐term cognitive outcomes in ischemic stroke <50 years of age. We propose further investigations of fibrinogen in relation to cognitive function in stroke in the young.

Quantification of Biological Responses as Predictors of Cognitive Outcome after Developmental TBI.

Successful translational studies within the field of Traumatic Brain Injury (TBI) are concerned with determining reliable markers of injury outcome at chronic time points. Determination of injury severity following Fluid Percussion Injury (FPI) has long been limited to the measured atmospheric pressure associated with the delivered pulse. Duration of unresponsiveness to toe pinch (unconsciousness) was next introduced as an extra marker of injury severity. The current study is an effort to assess the utilization of acute injury-induced biological responses (duration of toe pinch unresponsiveness, percent body weight change, quantification of brain edema, and apnea duration) to predict cognitive performance at a subacute time point following developmental brain injury. Cognitive performance, when measured at a subacute phase, after developmental FPI was negatively correlated with the following variables, duration of toe pinch unresponsiveness, percent weight change, and quantified level of brain edema. These finding suggest the potential utilization of reliable severity assessment of injury-induced biological responses in determining outcome measures at subacute time points.

Predictors of cognitive outcome in ventilated early rehabilitation patients

After weaning failure, patients who are transferred from intensive care units to early rehabilitation centers (ERC) not only suffer from motor deficits but also from cognitive deficits. It is still uncertain which patient factors have an impact on cognitive outcome at the end of early rehabilitation. Investigation of predictors of cognitive performance for initially ventilated early rehabilitation patients. A total of 301 patients (mean age 68.3± 11.4 years, 67% male) were consecutively enrolled in an ERC for aprospective observational study between January 2014 and December 2015. To investigate influencing factors on cognitive outcome operationalized by the neuromental index (NMI), we collected sociodemographic data, parameters about the critical illness, comorbidities, weaning and decannulation as well as different functional scores at admission and discharge and carried out multivariate analyses by ANCOVA. Of the patients 248 (82%) were successfully weaned, 155 (52%) decannulated and 75patients (25%) died of whom 39 (13%) were under palliative treatment. For the survivors (n= 226) we could identify independent predictors of the NMI at discharge from the ERC in the final sex and age-adjusted statistical model: alertness and decannulation were positively associated with the NMI whereas hypoxia, cerebral infarction and traumatic brain injury had anegative impact on cognitive ability. The model justifies 57% of the variance of the NMI (R2= 0.568) and therefore has ahigh quality of explanation. Because of increased risk of cognitive deficits at discharge of ERC, all patients who suffered from hypoxia, cerebral infarction or traumatic brain injury should be intensively treated by neuropsychologists. Since decannulation is also associated with positive cognitive outcome, arapid decannulation procedure should also be an important therapeutic target, especially in alert patients.

Abstract 172: Medical and Demographic Predictors of Long-term Cognitive Outcomes of Pediatric Stroke

Introduction: Studies examining cognitive outcomes for pediatric stroke are sparse, and few account for stroke severity. The Pediatric Stroke Outcome Measure (PSOM) provides an objective, comprehensive rating of neurological impairment. This study investigated the relationship between initial PSOM score and long-term cognitive outcomes. It was hypothesized that greater severity of stroke (worse initial PSOM score) would predict lower IQ at long-term follow-up. Other factors considered were age at stroke and months post stroke. Age-related studies in broad cognitive outcomes for pediatric stroke are sparse and somewhat inconsistent in findings. It was hypothesized that severity of stroke would be more relevant than age of stroke for long-term cognitive outcomes. Methods: PSOM scores at initial visit and IQ scores at long-term follow-up (M=3.77 years) were obtained for 84 survivors of pediatric stroke ages 4:0-25:6 (M=11:5 years; 37 females). A one-sample t-test was conducted to compare mean IQ to the normative sample. To examine the hypotheses, all variables of interest (PSOM, age at stroke, and months s/p) were entered into a stepwise regression equation. Results: Mean IQ for the sample was 84.77 (SD=17.26), significantly below average relative to healthy norms ( t =-8.088, p =.000). PSOM scores ranged 0-5.5 (median/mode=1.0). The regression was significant ( F =8.798; p =.000), with both PSOM score ( b =-.350; t [80]=-3.483; p =.001) and months post stroke ( b =-.355; t [80]=-3.005; p =.004) significantly contributing to the model, but not age at stroke. Conclusions: PSOM was more relevant than age at stroke in predicting long-term cognitive outcomes, and greater stroke severity was associated with lower IQ at follow-up. Finding suggest that initial PSOM score and greater time since stroke may be more relevant to long-term cognitive outcomes than age at stroke. The present study lends validity to using the PSOM both as a marker of functional severity of stroke and a potential indicator of relative risk for poorer long-term cognitive outcomes. Better predictors of cognitive outcomes for pediatric stroke are greatly needed in order to facilitate earlier intervention/rehabilitation and improve the efficacy of such efforts.