Impaired Processing Speed Research Articles

Intrinsic functional brain connectivity is resilient to chronic hypoperfusion caused by unilateral carotid artery stenosis

IntroductionChronic cerebral hypoperfusion caused by asymptomatic high-grade stenosis of the internal carotid artery (ICA) has been associated with impaired cognitive function. Only few studies exist on underlying changes of functional connectivity (FC). Methods20 patients with unilateral high-grade ICA stenosis without MRI lesions and 25 aged-match controls underwent resting-state functional MRI (rsfMRI) and neuropsychological assessment. Patients were examined within ten days before and 6–10 weeks after surgical or interventional revascularization of carotid stenosis. We examined mean resting-state FC ipsi- and contralateral to stenosis and network topology using graph-theoretical measures. ResultsAt baseline, intrahemispheric FC was similar for patients and healthy controls. After revascularization mean FC increased moderately without an effect on network topology. Patients performed worse in TMT B and Stroop test, while performance in global screening tests for dementia (Mini Mental Status Examination, DemTect) were comparable. Test results did not improve after revascularization. ConclusionIn our study population, we find no effect of chronic hypoperfusion on FC and global cognitive function, although we observe minor impairments in processing speed and mental flexibility. The subtle increase of FC after revascularization could indicate excessive upregulation after restoration of perfusion. However, it might as well be a coincidental finding due to the limited sample size.

Comparison of analgesic efficacy between erector spine plane block and intravenous patient-controlled analgesia with morphin after open heart surgery

Pain after cardiac surgery is always an obsession of patients and a top concern of anesthesiologists. Experimental subjects challenged by acute pain and patients in chronic pain experience impairments in attention control, working memory, mental flexibility, problem solving, and information processing speed. The two most commonly used analgesia methods are patient-controlled analgesia (PCA) and erector spinea plane block (ESP). Our study aimed to compare the analgesic effect of ESP with PCA in patients after cardiac surgery using extracorporeal circulation and evaluate the disavantages of these two pain relief techniques. Subject and methods: This study was a randomized controlled intervention study of adult patients who underwent open-heart surgery patients with extracorporeal circulation from May 2020 to September 2021 in the Department of Anesthesiology and Intensive Care Unit - Hanoi Heart Hospital. Results: Two hundred and four (204) consecutive patients were collected, included 108 patients in the ESP group and 96 patients in the PCA group. The mean intraoperative fentanyl amount in the ESP group (0.57±0.50 mg) was lower than in the PCA group (1.00±0.00 mg) (p<0.05). The average VAS score when the patient was lying still and taking deep breaths at the time of assessment in both groups was below 3 (corresponding to low pain level) (p>0.05). The mean morphin consumption 24 hours after surgery was significantly lower in the ESP group (0,23±0,12 mg) than in the PCA group (17,92±3,32 mg) (p<0.05). The mean time after surgery in the ESP group (3.80±1.02 hours) and the PCA group (5.21±1.10 hours) had a clear difference between p<0.05. The mean time of extubation in the ESP group (8.06±1.60 hours) was statistically significantly lower than in the PCA group (8.83±1.43 hours) (p<0.05). The rate of nausea in the ESP group (20.98%) was lower than in the PCA group (58.33%) (p<0.05). Conclusion: Both methods had good analgesic effect with an average VAS score ≤ 3. The ESP group had a lower mean postoperative morphine consumption, a higher patient satisfaction level, and a lower rate of nausea, vomiting, and slow breathing statistically significant less than the PCA group.

Targeted cognitive game training enhances cognitive performance in multiple sclerosis patients treated with interferon beta 1-a

BackgroundPrevention of cognitive decline in Multiple Sclerosis (MS) is of major importance. We explored the effect of a 6 months computerized game training program on cognitive performance in MS patients with mild cognitive impairment.MethodsThis was a single-center, randomized prospective study. We enrolled in this study 100 eligible MS patients treated with Interferon-beta-1a (Rebif). All had mild cognitive impairment in either executive function or information processing speed. Patients were randomized 1:1 to either use the cognitive games platform by HappyNeuron (HN) or receive no intervention. Executive function and information processing speed scores were measured at 3 and 6 months from baseline to evaluate the effect of game training on cognitive scores.ResultsIn both executive function and information processing speed, the game Training group showed significant improvement after 3 and 6 months. The Non-Training group showed mild deterioration in both domains at 3 months, and further deterioration that became significant at 6 months in executive function. Furthermore, at 6 months, the percent of patients in the Training group that improved or remained stable in both cognitive domains was significantly higher compared to the Non-Training group.ConclusionsOur findings suggest that cognitive game training has a beneficial effect on cognitive performance in MS patients suffering from mild cognitive impairment. While further evaluation is required to assess the longevity of that effect, we nonetheless recommend to MS patients to be engaged in cognitive gaming practice as part of a holistic approach to treating their condition.

Cerebral amyloid angiopathy and visuospatial functioning: Analysis of the clock drawing test

AbstractBackgroundCerebral amyloid angiopathy (CAA) contributes to cognitive impairment as well as dementia in the elderly. In clinical cohorts, symptomatic CAA is associated with impairments in executive function and processing speed. Because CAA severity tends to be highest in the occipital and posterior temporal and parietal lobes, it may also affect visuospatial function. We hypothesized that participants with a clinical diagnosis of CAA will have impaired performance on tests of visuospatial function when compared to control, mild cognitive impairment (MCI) and Alzheimer’s disease (AD) participants.MethodParticipants with CAA presented with lobar intracerebral hemorrhage, transient focal neurological episodes, or mild cognitive impairment; met Boston criteria for probable CAA; and did not have dementia. Clocks were scored based on a published 20‐point system (Mendez, JAGS 1992). Clock items were subcategorized by general contours, number items, and hand items (Mendez, JAGS 1992); and by a subset of 9 items correlated in prior literature with visuospatial function and temporal‐parietal hypoperfusion (visuospatial items).ResultData from 53 CAA without dementia, 43 MCI, 30 AD with mild dementia (MMSE ≥20), and 40 control participants were analyzed (mean age 71.6 [SD 7.5]; 47% women). Compared to controls, CAA participants performed significantly worse on total score, hand items, and visuospatial items (Table 1). AD participants performed worse than controls on all components except general contour, and MCI participants did not differ from controls. Among CAA participants, total and visuospatial scores did not correlate with history of stroke, number of microbleeds, or white matter hyperintensity volume (p>0.10).ConclusionMean performance on the clock drawing test is lower in CAA patients without dementia than controls, suggesting visuospatial impairment. This impairment may be related to vascular amyloid deposition in posterior brain regions; however, it was not correlated with typical markers of CAA severity suggesting it may be an early but not necessarily progressive feature. Future research should investigate the mechanisms of visuospatial impairment in CAA—including whether it is related to posterior white matter damage or parieto‐occipital atrophy—and its association with daily function and risk for cognitive decline.

Cognitive impairments in treatment-resistant depression: Results from the French cohort of outpatients (FACE-DR)

• Patients suffering from treatment resistant-depression present cognitive impairments in executive function, verbal memory and processing speed. • Depression intensity is associated with poorer performance in processing speed and verbal memory. • Impairments in executive function and attention are associated with poorer daily functioning. • Adjusted psychotherapy and cognitive remediation should be proposed to patients suffering from treatment resistant-depression. Previous studies set out cognitive impairments in major depression. However, only two studies were performed among patients suffering from treatment-resistant depression (TRD) and conducted on limited sample sizes. Here, we aimed to characterize cognitive impairments in TRD, and their association with the severity of depression and daily functioning. We included 288 patients suffering from TRD (178 women, 52.5 ± 13.1 years old). They undertook sociodemographic, clinical, daily functioning and neuropsychological testing (TMT, Baddeley task, verbal fluencies, WAIS-4 subtests, D2 and RLRI-16). We compared our patients’ performances to theoretical performances of the general population. TRD was associated with poorer neuropsychological performances, except for similarities task. We found an effect of depression severity on processing speed and memory, and an impact on daily functioning affecting memory, selective attention and executive function. Patients suffering from TRD have significant cognitive impairments. Therapeutic interventions should be developed to manage such impairments.

Cognition differentiates gait speed among older adults

AbstractBackgroundThe ability to perform a motor and cognitive dual‐task (DT) becomes more challenging as one ages and shows a greater deficit, if one has a cognitive impairment (CI). CI has also been shown to predict a decline in physical functioning. Therefore, the purpose was to examine differences between cognitively healthy (CN) and cognitively impaired (CI) older adults on gait speed (GS) during habitual (HAB) and fast (FAST) walking trials with and without a DT.Method83 older adults (80.66±5.36) completed a digital Visual Paired Comparison (VPC) cognitive assessment, which measured working memory, and a Digital Symbol (DS) cognitive assessment, which measured processing speed. Participants were grouped into CN or CI based on their results for each assessment. Subjects performed two trials of each walking test: HAB, FAST, HAB‐DT, and FAST‐DT. The DT trials were performed using a working memory task. GS was calculated using the time to cover 10m. One‐way ANOVA was used to assess for differences in GS between VPC and DS cognitive groups.ResultWhile HAB GS (p=.10) was not significantly different between the VPC cognitive groups, the CN group walked significantly faster than the CI group during the FAST, HAB DT, and FAST DT trials (p<.05). There was not a significant difference in HAB GS (p=.10) or HAB DT GS (p=.08) between the CI and CN DS groups. However, the DS CI group walked significantly slower during the FAST (p=.03) and FAST DT (p=.05) assessments.ConclusionIndividuals with CI showed no statistical difference in habitual walking speed. However, this was clinically meaningful as the individuals with an average or above average working memory and processing speed walked faster than individuals with CI by 8.4% and 6.5%, respectively. While GS declined during the DT trials, individuals with a working memory impairment showed a greater decline, and it was even larger during the fast DT trials and for individuals with a working memory (19.5%) or processing speed (17.6%) impairment. Previous research has suggested DT walking involves activation of the prefrontal cortex, which may partially explain the greater decline in DT GS for those with working memory impairment.

Serum Vitamin D as a Marker of Impaired Information Processing Speed and Early Disability in Multiple Sclerosis Patients.

Slowed information processing speed (IPS) is the hallmark and first cognitive domain to be altered in multiple sclerosis (MS) patients. Insufficient serum vitamin D was previously associated with disease development, relapses, and progression, but little is reported on cognition. However, vitamin D and cognitive impairment (CI) in other neurodegenerative diseases have already been linked. We explored the possible correlation between vitamin D and IPS at diagnosis and early disability at last follow-up in 81 MS patients. At diagnosis, we collected vitamin D levels and performed a Symbol Digit Modalities Test (SDMT). Raw scores were adjusted for age, gender, and educational level. Early disability was evaluated with MS severity score (MSSS) and age-related MSSS (ARMSS). A total of 71 patients (86.58%) showed hypovitaminosis D (19.71 ± 8.76 ng/mL) and 18 patients (21.95%) had CI. Patients with CI showed severe hypovitaminosis D (p = 0.004). No patients with sufficient vitamin D levels had CI. We found a positive correlation between vitamin D levels at diagnosis and (1) SDMT raw and z-score that persisted after correction for sunlight exposure and MRI baseline characteristics, and (2) EDSS, MSSS, and ARMSS after a mean 2 year follow-up. Low vitamin D levels may affect both cognition and early disability in newly diagnosed MS patients.

Why and how to evaluate driving abilities in patients with neurodegenerative diseases?

Many studies have shown that individuals with neurodegenerative diseases are at risk of being involved in a traffic accident. However, driving is critical for social integration and independence in daily life. The lack of consensus and a standardised assessment of driving abilities in these patients is problematic. This article summarises the various multidisciplinary evaluations proposed, their limits and the societal issues raised by such an evaluation. Several theoretical neuropsychological models have attempted to describe the cognitive processes involved in car driving. Moreover, several studies into neurodegenerative diseases have sought to determine which alterations to cognitive functions best explain driving errors. In this article, we describe the relationships between neuropsychological performance and driving abilities for the most frequent neurodegenerative disorders. It appears that a full neuropsychological assessment is necessary to accurately determine which patients are at risk of dangerous driving. In particular, cognitive impairments in attention, visual-spatial abilities, executive functions, and/or information processing speed appear to be the most likely to be involved in driving errors.

OS05.4.A Do neurocognitive deficits explain the differences between brain tumour patients and their proxies assessing the patient’s I-ADL?

Abstract BACKGROUND Neurocognitive deficits are common among brain tumour patients, and may impact on patient awareness of deficits in instrumental activities in daily life (IADL). This study aimed to examine differences between patient-reported and proxy-reported assessments of the patient’s performance of IADL, and whether the level of (dis)agreement is associated with neurocognitive deficits. MATERIAL AND METHODS A phase III EORTC questionnaire measuring IADL in brain tumour patients (EORTC IADL-BN32) and six neurocognitive test measures were administered as part of a larger multicentre international study designed to develop a brain tumour specific IADL questionnaire. Bland-Altman plots and Mann-Whitney U tests were used to evaluated patient- and proxy-reported IADL on a group level. Subsequently, Mann-Whitney U tests were performed to compare patient-proxy difference scores (patient IADL score - their proxy IADL score) between patients who were considered clearly neurocognitively impaired (≥2 neurocognitive test measures; ≤2.0 SD below healthy controls) and patients who were not. Furthermore, multinomial logistic regression analyses were performed to examined which sociodemgraphic, clinical, and particularly neurocognitive variables were independently associated with patients and proxies differing in their evaluation of patient’s IADL. RESULTS Patients (N=81) and proxies (N=81), on group level, did not significantly differ on either the IADL individual item or scale scores. However, significant differences were found on patient-proxy difference scores between patients who were (N=37) and were not (N=44) considered clearly neurocognitively impaired for 10/32 individual items and one of the scales (i.e. Scale 4: Administrative tasks), all showing that the proxies of clearly neurocognitively impaired patients reported more problems relative to the patients themselves, compared to proxies of patients not clearly neurocognitively impaired. Furthermore, for each scale, a neurocognitive variable, either impaired information processing speed, cognitive flexibility, verbal fluency or the number of neurocognitive test measures impaired, was found to be independently associated with proxies reporting more problems. For 4/5 scales, a clinical variable was additionally independently associated with proxies reporting more problems. Only one variable was independently associated with patient reporting more problems, namely being in active treatment was found to be associated with patients reporting more problems on Scale 4: Administrative tasks. CONCLUSION Results imply a consistent trend of clearly neurocognitively impaired patients underreporting problems with IADL compared to their proxies. It would therefore be advised to administer both the patient- and proxy-version of the EORTC IADL-BN32, particularly if neurocognitive deficits are presumed.

Factors associated with employment stability following traumatic brain injury, in a sample who have received comprehensive vocational rehabilitation

Purpose To quantify employment stability of individuals with traumatic brain injury (TBI) who received comprehensive vocational rehabilitation (VR) using different measures to identify difficulties experienced and factors associated with employment stability. Materials and methods 72 individuals with predominantly moderate-severe TBI were interviewed. Neuropsychological assessment scores were collected. Three employment stability measures were used: number of post-injury employers, duration with employer and average weekly hours. Descriptive and predictive analyses were performed. Results 90.2% remained employed at time of interview (Mean = 4.83 years post-injury). However, participants worked significantly fewer hours, 63.9% had changed roles or employers at least once and only 51% achieved their pre-injury level of responsibility. 61% reported a high level of employer support. Self-reported difficulties included physical sequelae, memory problems and fatigue. Post-injury testing found impaired memory (34.4%) and processing speed (49.2%). After accounting for time since injury, demographic and employment variables (older age, male gender, higher pre-injury skill-level, higher level of employer support), higher level of injury-related difficulties and lower level of cognitive function significantly predicted employment stability. Conclusion Injury-related difficulties impact employment long-term, necessitating ongoing work modifications. Individualised VR is important, not only to facilitate return to work but to support long-term employment stability after TBI. Implications for rehabilitation Being male was associated with working more hours, and having faster processing speed, lower levels of fatigue and ongoing physical sequelae were associated with a longer duration with the same employer. Initial return to work is often the first step on a long journey as injury-related difficulties can continue to impact work in the-long term and require lasting modifications to duties and working hours. VR should include ongoing follow-up to facilitate work modifications and support both the employer and the employee in adjusting to these. VR should be individualised to support the impact of the unique cognitive and physical limitations experienced by each individual with TBI, based on the needs and employment demands of each workplace.

Regional Cerebellar Volume Loss Predicts Future Disability in Multiple Sclerosis Patients

Cerebellar symptoms in multiple sclerosis (MS) are well described; however, the exact contribution of cerebellar damage to MS disability has not been fully explored. Longer-term observational periods are necessary to better understand the dynamics of pathological changes within the cerebellum and their clinical consequences. Cerebellar lobe and single lobule volumes were automatically segmented on 664 3D-T1-weighted MPRAGE scans (acquired at a single 1.5 T scanner) of 163 MS patients (111 women; mean age: 47.1 years; 125 relapsing–remitting (RR) and 38 secondary progressive (SP) MS, median EDSS: 3.0) imaged annually over 4 years. Clinical scores (EDSS, 9HPT, 25FWT, PASAT, SDMT) were determined per patient per year with a maximum clinical follow-up of 11 years. Linear mixed-effect models were applied to assess the association between cerebellar volumes and clinical scores and whether cerebellar atrophy measures may predict future disability progression. SPMS patients exhibited faster posterior superior lobe volume loss over time compared to RRMS, which was related to increase of EDSS over time. In RRMS, cerebellar volumes were significant predictors of motor scores (e.g. average EDSS, T25FWT and 9HPT) and SDMT. Atrophy of motor-associated lobules (IV-VI + VIII) was a significant predictor of future deterioration of the 9HPT of the non-dominant hand. In SPMS, the atrophy rate of the posterior superior lobe (VI + Crus I) was a significant predictor of future PASAT performance deterioration. Regional cerebellar volume reduction is associated with motor and cognitive disability in MS and may serve as a predictor for future disease progression, especially of dexterity and impaired processing speed.

Southwestern Assessment of Processing Speed (SWAPS): A new brief test with demographically-corrected norms in an ethnically and educationally diverse population

Objective. Neuropsychological measures of processing speed have long been used as sensitive indices of cognitive functioning. Most of these commonly used tests are proprietary, and there is a need for brief, freely available tools that can be used in diverse clinical and research settings. The Southwestern Assessment of Processing Speed (SWAPS) is a 60-second digit-symbol transcription task developed as a brief alternative to commercially available coding tests. Demographically-corrected normative data are presented along with reliability and sensitivity/specificity values in older adults with and without cognitive impairment. Method. SWAPS data from 915 healthy aging individuals (NC) and 858 subjects with clinical diagnoses of mild cognitive impairment (MCI; n = 430) and Alzheimer’s disease clinical syndrome (ADCS; n = 428) were obtained from the Texas Alzheimer’s Research and Care Consortium (TARCC). TARCC participants represent ethnically and educationally diverse community-dwelling individuals age 50+. Results. SWAPS scores showed the expected associations with age, sex, and education, and the interaction between age and education were significant predictors of SWAPS scores. Test-retest reliability in NC was good, and the SWAPS distinguished impaired and non-impaired groups with adequate to excellent sensitivity and specificity for the primary analyses, with optimal cut-off points provided. Raw score- to uncorrected normalized T-scores and demographically-corrected SWAPS T-scores using regression-based norms are presented along with scoring programs for the calculation of each. Conclusions. The SWAPS is a brief, free, easily administered test with demographically-corrected regression-based norms and promising utility for detection of cognitive impairment and efficient assessment of processing speed.

Is processing speed a valid neurocognitive endophenotype in bipolar disorder? Evidence from a longitudinal, family study

BackgroundSubstantial evidence supports the existence of neurocognitive endophenotypes in bipolar disorder (BD), but very few longitudinal studies have included unaffected relatives. In a 5-year, follow-up, family study, we have recently suggested that deficits in manual motor speed and visual memory could be endophenotype candidates for BD. We aimed to explore whether this also applies to processing speed. MethodsA sample of 348 individuals, including 163 BD patients, 65 unaffected first-degree relatives (BD-Rel) and 120 genetically unrelated healthy controls (HC), was assessed with the Digit Symbol Substitution Test (DSST) on two occasions over a 2-year period (T1, T2). DSST values were controlled for age, years of education, occupational status, and subsyndromic mood symptoms. Differences between groups were evaluated with ANCOVAs. ResultsAt T1 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.38) and BD-Rel (p < 0.001; Cohen's d = 0.82). BD-Rel showed an intermediate performance with significant differences with HC (p < 0.01; Cohen's d = 0.50). Similarly, at T2 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.44) and BD-Rel (p < 0.01; Cohen's d = 0.51). BD-Rel performance was intermediate and significantly lower than that of HC (p < 0.01; Cohen's d = 0.97). A Repeated Measures ANOVA revealed no significant between-group differences in performance over time (p > 0.05). ConclusionsThe results of this longitudinal, family study suggest that impaired processing speed may represent a suitable cognitive endophenotype for BD. Further research on the field is required to confirm these preliminary findings.

Psychopathological Symptom Load and Distinguishable Cerebral Blood Flow Velocity Patterns in Patients With Schizophrenia and Healthy Controls: A Functional Transcranial Doppler Study.

Introduction: Schizophrenia is a severe psychiatric disorder, with executive dysfunction and impaired processing speed playing a pivotal role in the course of the disease. In patients with schizophrenia, neurocognitive deficits appear to be related to alterations in cerebral hemodynamics. It is not fully understood if psychopathological symptom load (i.e., presence and severity of symptoms) is also related to alterations in cerebral hemodynamics. We aim to study the relationship between psychopathological symptom load and cerebral hemodynamics in the Middle Cerebral Artery (MCA) during a cognitive task in patients with schizophrenia and healthy controls.Methodology: Cerebral hemodynamics in the MCA were examined in 30 patients with schizophrenia and 15 healthy controls using functional Transcranial Doppler (fTCD) during the Trail Making Test (TMT). Psychopathological symptoms were measured using the Brief Psychiatric Rating Scale (BPRS). Patients were dichotomized according to BPRS scores: mild-moderate (BPRS < 41, n = 15) or marked-severe (BPRS ≧ 41, n = 15). Mean blood flow velocity (MFV) in the MCA and processing speed of the TMT were analyzed. Cerebral hemodynamics were analyzed using the general additional model (GAM) with a covariate analysis of variance (ANCOVA) for group comparisons.Results: Patients and healthy controls were comparable regarding demographics. Patients had a slower processing speed for the TMT-A (patients-severe: 52s, patients-moderate: 40s, healthy-controls: 32s, p = 0.019) and TMT-B [patients-severe: 111s, patients-moderate: 76s, healthy-controls: 66s, p < 0.001)]. Patients demonstrated differing hemodynamic profiles in both TMTs: TMT- A [F(6, 1,792) = 17, p < 0.000); TMT-B [F(6, 2,692) = 61.93, p < 0.000], with a delay in increase in MFV and a failure to return to baseline values.Conclusions: Patients with schizophrenia demonstrated slower speeds of processing during both the TMT-A and TMT-B. The speed of processing deteriorated with increasing psychopathological symptom load, additionally a distinct cerebral hemodynamic pattern in the MCA was observed. Our results further support the view that severity of schizophrenia, particularly psychopathological symptom load, influences performance in neurocognitive tasks and is related to distinct patterns of brain hemodynamics.

Is computerized screening for processing speed impairment sufficient for identifying MS-related cognitive impairment in a clinical setting?

BackgroundAnnual screening for processing speed impairment (PSI) is recommended for patients with multiple sclerosis (pwMS). However, cognitive deficits in pwMS are heterogeneous, and whether PSI screening identifies patients with impairment in other cognitive domains is unclear. The objective of this study was to examine sensitivity and specificity of the self-administered, computerized Processing Speed Test (PST) in identifying cognitive impairment defined by a comprehensive neuropsychological battery (NPT). MethodsNinety-one pwMS completed PST and NPT, with raw scores demographically adjusted. Cognitive impairment on NPT was defined as performance <5th percentile in at least one domain. Receiver operating characteristic (ROC) analyses were performed to determine the ability of the PST to discriminate between cognitively normal (CN) and cognitively impaired with PSI (CI-PSI) and cognitively impaired with normal processing speed (CI-PSN) groups. ResultsCognitive impairment was observed in 23.1% of pwMS on PST and in 42.9% on NPT. PST demonstrated excellent ability to discriminate between CN (57.1%) and CI-PSI (20.9%) groups (Area Under the Curve [AUC] = 0.86, p < 0.001). In contrast, PST was unable to discriminate CN and CI-PSN (22.0%) groups (AUC = 0.42, p = 0.32). ConclusionThe PST demonstrates excellent ability to detect PSI in pwMS but is unable to identify cognitively impaired pwMS without PSI, highlighting the importance of developing additional screening measures.

Why and how evaluating driving abilities in patients with neurodegenerative diseases?

Many studies have shown that individuals with neurodegenerative diseases are a risk factor for being involved in a traffic accident. However, driving is critical for social integration and independence in daily life. Lack of consensus and standardized assessment of driving abilities in these patients is problematic. This article summarizes the various multidisciplinary evaluations proposed, their limits, and the societal issues raised by such an evaluation. Several neuropsychological theoretical models have attempted to describe the cognitive processes involved in car driving. Moreover, several studies have sought to determine which cognitive functions are impaired in distinct disorders and best explained driving errors. We here describe the relationships between neuropsychological performance and driving abilities for the most frequent neurodegenerative disorders. It appears that a full neuropsychological assessment is necessary to determine accurately which patients are at risk of dangerous driving. In particular, cognitive impairments in attention, visual-spatial abilities, executive functions, and/or information processing speed appear to be the most likely involved in driving errors.

A Longitudinal Study of White Matter Functional Network in Mild Traumatic Brain Injury.

Some patients after mild traumatic brain injury (mTBI) experience microstructural damages in the long-distance white matter (WM) connections, which disrupts the functional connectome of large-scale brain networks that support cognitive function. Patterns of WM structural damage following mTBI were well documented using diffusion tensor imaging (DTI). However, the functional organization of WM and its association with gray matter functional networks (GM-FNs) and its DTI metrics remain unknown. The present study adopted resting-state functional magnetic resonance imaging to explore WM functional properties in mTBI patients (108 acute patients, 48 chronic patients, 46 healthy controls [HCs]). Eleven large-scale WM functional networks (WM-FNs) were constructed by the k-means clustering algorithm of voxel-wise WM functional connectivity (FC). Compared with HCs, acute mTBI patients observed enhanced FC between inferior fronto-occipital fasciculus (IFOF) WM-FN and primary sensorimotor WM-FNs, and cortical primary sensorimotor GM-FNs. Further, acute mTBI patients showed increased DTI metrics (mean diffusivity, axial diffusivity, and radial diffusivity) in deep WM-FNs and higher-order cognitive WM-FNs. Moreover, mTBI patients demonstrated full recovery of FC and partial recovery of DTI metrics in the chronic stage. Additionally, enhanced FC between IFOF WM-FN and anterior cerebellar GM-FN was correlated with impaired information processing speed. Our findings provide novel evidence for functional and structural alteration of WM-FNs in mTBI patients. Importantly, the convergent damage of the IFOF network might imply its crucial role in our understanding of the pathophysiology mechanism of mTBI patients.

Advanced glycation end products and cognitive impairment in schizophrenia.

Advanced glycation end products play a key role in the pathophysiology of schizophrenia. Cognitive impairment is one of the central features of schizophrenia; however, the association between advanced glycation end products and cognitive impairment remains unknown. This study investigated whether advanced glycation end products affect the cognitive domain in patients with schizophrenia. A total of 58 patients with chronic schizophrenia were included in this cross-sectional study. Plasma advanced glycation end products were measured using high-performance liquid chromatography (HPLC). Neuropsychological and cognitive functions were assessed using the Wechsler Adult Intelligence Scale, Third Version, and the Wisconsin Card Sorting Test Keio-FS version. Multiple regression analysis adjusted for age, sex, body mass index, educational years, daily dose of antipsychotics, and psychotic symptoms revealed that processing speed was significantly associated with plasma pentosidine, a representative advanced glycation end product (standardized β = -0.425; p = 0.009). Processing speed is the cognitive domain affected by advanced glycation end products. Considering preceding evidence that impaired processing speed is related to poor functional outcome, interventions targeted at reducing advanced glycation end products may contribute to promoting recovery of patients with schizophrenia as well as cognitive function improvement.

Late health outcomes in survivors of Wilms tumor: A report from the St. Jude Lifetime (SJLIFE) cohort study.

10038 Background: We aimed to characterize late health, neurocognitive, and physical performance outcomes among survivors of Wilms tumor. Methods: Wilms tumor survivors (n = 280), ≥ 5 years from diagnosis, participating in SJLIFE were clinically assessed along with a community control sample (n = 625). Health outcomes were graded per a modified Common Terminology Criteria for Adverse Events (grade 1 [mild] to grade 4 [life threatening]). Standardized neurocognitive testing was graded using age-adjusted z-scores. Aerobic function (six-minute walk), mobility (timed up and go) and flexibility (sit and reach) were assessed. Associations between treatment exposures and prevalent conditions were examined by multivariable logistic regression, adjusted for current age, sex and race. Results: Survivors (59% female, 73% white), median age 3 years (range 0-15) at diagnosis and 31 years (9-58) at evaluation, were comprehensively evaluated on the St. Jude campus. Two-thirds (67%) were treated with doxorubicin (median dose 175 mg/m2 range 52-490), 167 (60%) received abdominal radiation (median dose 12 Gy range 8.8-61.2) and 25% received chest radiation (12 Gy range 9-44). By age 40 years, survivors averaged 12.7 (95% confidence interval [CI] 11.7-13.8) grade 1-4 and 7.5 (CI 6.7-8.2) grade 2-4 conditions, compared to 4.2 (CI 3.9-4.6) and 2.3 (CI 2.1-2.5), respectively, among controls. The most prevalent medical conditions (grade ≥ 2) are reported in the table. Abnormal glucose metabolism was associated with abdominal radiation (relative risk [RR] 5.1 CI 1.4-19.0); restrictive pulmonary defects with chest radiation (RR 24.0 CI 3.2-180); and cardiomyopathy (RR 15.6 CI 1.9-128), pulmonary diffusion (RR 4.5 CI 1.3-15.1), and chronic kidney disease (RR 4.5 CI 1.3-16.1) with doxorubicin exposure. Survivors had a three-fold higher risk (standardized incidence ratio 3.5, CI 2.2-6.6) for subsequent neoplasms. Impairments (grade ≥ 2) in executive function (20% vs. 12%), attention (17% vs. 9%), memory (21% vs. 10%), and processing speed (20% vs. 8%) were more frequent in survivors than controls (p &lt; 0.05). Impairments in aerobic function (13.6%), mobility (13.6%), and flexibility (11.1%) were higher than expected (p &lt; 0.01). Significant associations were not identified between treatment exposures and neurocognitive or physical performance outcomes. Conclusions: Systematic clinical assessment identified a significant burden of chronic health conditions and previously unrecognized neurocognitive and physical performance limitations in survivors of Wilms tumor.[Table: see text]

Effects of metabolic syndrome on cognitive outcomes in long-term survivors of childhood cancer.

12013 Background: Childhood cancer therapy increases risk for cognitive impairment and other chronic conditions, which also may impact cognition. We assessed the unique impact of metabolic syndrome (MetS) on cognition in survivors participating in the St. Jude Lifetime Cohort Study. Methods: Participants included 4058 survivors of childhood cancer (53.9% female; mean [SD] age 30.1 [10.5] years at evaluation; 22.6 [10.1] years from diagnosis) who completed clinical evaluation and cognitive testing. MetS criteria followed Adult Treatment Panel III guidelines (at least 3 of: hypertension, high triglycerides, abdominal obesity, low high-density lipoprotein [HDL], high fasting glucose). Multivariable log-binomial regression models assessed risk of cognitive impairment associated with MetS stratified by survivors who did (n = 2301) or did not (n = 1757) receive central nervous system (CNS)-directed therapy. Mediation analysis assessed effects of MetS and physical activity in cranial radiotherapy (CRT)-associated cognitive impairment. Models were adjusted for age, sex, follow-up time and treatment exposures. Results: MetS was associated with increased risk of impaired attention (relative risk [RR] 1.34 95% confidence interval [CI] 1.07-1.66), processing speed (RR 1.25 CI 1.11-1.41) and executive function (RR 1.18 CI 1.01-1.37) in survivors with CNS-directed therapy and academic achievement (RR 1.84 CI 1.18-2.89), attention (RR 1.43 CI 1.10-1.87), and processing speed (RR 1.46 CI 1.21-1.75) in those without CNS-directed therapy. MetS components associated with cognitive impairment included abdominal obesity (memory RR 1.34 CI 1.13-1.59; processing speed RR 1.41 CI 1.24-1.59; executive function RR 1.21 CI 1.05-1.39) and low HDL (intelligence RR 1.26 CI 1.06-1.49; attention RR 1.27 CI 1.03-1.57; processing speed RR 1.17 CI 1.01-1.35; executive function RR 1.20 CI 1.05-1.37) in survivors with CNS-directed therapy. In survivors treated without CNS-directed therapy hypertension (academic achievement RR 1.49 CI 1.18-1.88; intelligence RR 1.34 CI 1.02-1.76; attention RR 1.42 CI 1.12-1.79; memory RR 1.45 CI 1.14-1.84; processing speed RR 1.30 CI 1.08-1.55; executive function RR 1.32 CI 1.08-1.62) and abdominal obesity (academic achievement RR 1.71 CI 1.07-2.72; processing speed RR 1.23 CI 1.02-1.49; executive function RR 1.38 CI 1.09-1.75) were associated with impairment. In mediation analyses, direct effects of CRT were identified, as were indirect effects through physical activity (processing speed β = 0.035 p &lt; 0.01; attention β = 0.03 p &lt; 0.01; executive function β = 0.172 p &lt; 0.01). Conclusions: MetS increases risk of cognitive impairment in survivors, particularly abdominal obesity, hypertension and low HDL. Physical activity appears to partially mediate impact of CRT on cognitive outcomes and is an important target for interventions to lower impairment risk.