Acute peri-operative neurocognitive disorders: a narrative review.

Peri-operative neurocognitive disorders are the most common complication experienced by older individuals undergoing anaesthesia and surgery. Peri-operative neurocognitive disorders, particularly postoperative delirium, result in long-term poor outcomes including: death; dementia; loss of independence; and poor cognitive and functional outcomes. Recent changes to the nomenclature of these disorders aims to align peri-operative neurocognitive disorders with cognitive disorders in the community, with consistent definitions and clinical diagnosis. Possible mechanisms include: undiagnosed neurodegenerative disease; inflammation and resulting neuroinflammation; neuronal damage; and comorbid systemic disease. Pre-operative frailty represents a significant risk for poor postoperative outcomes; it is associated with an increase in the incidence of cognitive decline at 3 and 12 months postoperatively. In addition to cognitive decline, frailty is associated with poor functional outcomes following elective non-cardiac surgery. It was recently shown that 29% of frail patients died or experienced institutionalisation or new disability within 90 days of major elective surgery. Identification of vulnerable patients before undergoing surgery and anaesthesia is the key to preventing peri-operative neurocognitive disorders. Current approaches include: pre-operative delirium and cognitive screening; blood biomarker analysis; intra-operative management that may reduce the incidence of postoperative delirium such as lighter anaesthesia using processed electroencephalography devices; and introduction of guidelines which may reduce or prevent delirium and postoperative neurocognitive disorders. This review will address these issues and advocate for an approach to care for older peri-operative patients which starts in the community and continues throughout the pre-operative, intra-operative, postoperative and post-discharge phases of care management, involving multidisciplinary medical teams, as well as family and caregivers wherever possible.

Suicidal ideation and executive functioning in pediatric cancer.

OBJECTIVE: Neurocognitive impairments and psychological distress are among the most common difficulties experienced by children treated for cancer. Elevated rates of suicidal ideation (SI) are documented among cancer survivors, and a link between neurocognitive deficits and SI is evident, yet the relationship between SI and pediatric cancer-related neurocognitive effects has not yet been studied. PARTICIPANTS AND METHODS: Participants were 166 pediatric cancer patients (57.8% Brain Tumor, 31.3% leukemia, 10.8% other cancers) aged 6-23 (M = 11.57, SD = 3.82; 45.8% female) referred for neuropsychological surveillance. SI prevalence was measured by parent, teacher, or patient endorsement of self-harm related items on informant-report measures (e.g., the Child Behavior Checklist). Executive functioning (Behavior Rating Inventory of Executive Function), ADHD symptoms (ADHD Rating Scale), and performance-based measures were compared between those with SI and those without. RESULTS: 17.5% of pediatric cancer patients experienced SI, of which 44.7% had self-endorsement only, 58.5% parent-endorsement only, 20.6% teacher-endorsement only, and 24.1% had two endorsements. Those with SI had significantly greater impairments in global executive composite scores by both parent- and teacher-report (ps < 0.05). Parents of children with SI endorsed significantly more inattention symptoms (M = 6.10, SD = 15.48) than those without SI (M = 50.56, SD = 8.70; p < 0.01), but hyperactivity symptoms did not differ. Intellectual and executive function performance did not differ between those with and without SI (ps > 0.1). CONCLUSIONS: An elevated number of children treated for cancer experience SI and related neurocognitive problems. Screening for SI and further assessment of the connection between executive functioning and SI in pediatric cancer populations is needed.

Neurocognitive, Quality of Life, and Behavioral Outcomes for Patients With Covert Stroke After Cardiac Surgery: Exploratory Analysis of Data From a Prospectively Randomized Trial.

BACKGROUND: Asymptomatic brain ischemic injury detected with diffusion-weighted magnetic resonance imaging (DWI) is reported in more than one-half of patients after cardiac surgery. There are conflicting findings on whether DWI-detected covert stroke is associated with neurocognitive dysfunction after surgery, and it is unclear whether such ischemic injury affects quality of life or behavioral outcomes. The purpose of this study was to perform exploratory analysis on whether covert stroke after cardiac surgery is associated with delayed neurocognitive recovery 1 month after surgery, impaired quality of life, anxiety, or depression. METHODS: Analysis of data collected in a prospectively randomized study in patients undergoing cardiac surgery testing whether basing mean arterial pressure (MAP) targets during cardiopulmonary bypass to be above the lower limit of cerebral autoregulation versus usual practices reduces the frequency of adverse neurological outcomes. A neuropsychological testing battery was administered before surgery and then 1 month later. Patients underwent brain magnetic resonance imaging (MRI) between postoperative days 3 and 5. The primary outcome was DWI-detected ischemic lesion; the primary end point was change from baseline in domain-specific neurocognitive Z scores 1 month after surgery. Secondary outcomes included a composite indicator of delayed neurocognitive recovery, quality of life measures, state and trait anxiety, and Beck Depression Inventory scores. RESULTS: Of the 164 patients with postoperative MRI data, clinical stroke occurred in 10 patients. Of the remaining 154 patients, 85 (55.2%) had a covert stroke. There were no statistically significant differences for patients with or without covert stroke in the change from baseline in Z scores in any of the cognitive domains tested adjusted for sex, baseline cognitive score, and randomization treatment arm. The frequency of delayed neurocognitive recovery (no covert stroke, 15.1%; covert stroke, 17.6%; P = .392), self-reported quality of life measurements, anxiety rating, or depression scores were not different between those with or without DWI ischemic injury. CONCLUSIONS: More than one-half of patients undergoing cardiac surgery demonstrated covert stroke. In this exploratory analysis, covert stroke was not found to be significantly associated with neurocognitive dysfunction 1 month after surgery; evidence of impaired quality of life, anxiety, or depression, albeit a type II error, cannot be excluded.

Galectin-1 ameliorates perioperative neurocognitive disorders in aged mice.

INTRODUCTION: The incidence of perioperative neurocognitive disorders (PND) is higher in the elderly patients undergoing surgery. Microglia activation-mediated neuroinflammation is one of the hallmarks of PND. Galectin-1 has been identified as a pivotal modulator in the central nervous system (CNS), while the role of galectin-1 in PND induced by microglia-mediated neuroinflammation is still undetermined. METHODS: An exploratory laparotomy model anesthetized with isoflurane was employed to investigate the role of galectin-1 on PND in aged mice. Open field test and Morris water maze were used to test the cognitive function 3- or 7-days post-surgery. The activation of microglia in the hippocampus of aged mice was tested by immunohistochemistry. Western blot, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to elucidate the underlying mechanisms. RESULTS: Galectin-1 attenuated the cognitive dysfunction induced by surgery in aged mice and inhibited microglial activity. Moreover, galectin-1 decreased the expression level of inflammatory proteins (interleukin-1ß, interleukin-6, and tumor necrosis factor-α), and prevented neuronal loss in the hippocampus. Galectin-1 inhibited the inflammation of BV2 microglial cells induced by lipopolysaccharide via decreasing the translocation of NF-κB p65 and c-Jun, while this kind of inhibition was rescued when overexpressing IRAK1. CONCLUSION: Our findings provide evidence that galectin-1 may inhibit IRAK1 expression, thus suppressing inflammatory response, inhibiting neuroinflammation, and improving ensuing cognitive dysfunction. Collectively, these findings unveil that galectin-1 may elicit protective effects on surgery-induced neuroinflammation and neurocognitive disorders.

Test Accuracy of the Montreal Cognitive Assessment in Screening for Early Poststroke Neurocognitive Disorder: The Nor-COAST Study.

BACKGROUND AND PURPOSE: We determined the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) for poststroke neurocognitive disorder defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria in a prospective observational study. METHODS: Consecutive participants able to complete a cognitive test battery and MoCA 3 months poststroke were included. The reference standard of neurocognitive disorder was defined as a score of ≥1.5 SD below the normative mean in ≥1 cognitive domain on the cognitive test battery. RESULTS: Among 521 participants (43.6% women; mean age/SD, 71.5/12.0 years; mean education/SD, 12.4/3.8 years), the area under the receiver operating characteristic curve of MoCA for neurocognitive disorder was 0.80 (95% CI, 0.76-0.84). Using the standard MoCA cutoff <26, sensitivity was 0.71 (0.69-0.79) with specificity of 0.73 (0.66-0.76). MoCA cutoff of <27 gave higher sensitivity (0.82 [0.77-0.85]) at the expense of specificity (0.60 [0.53-0.66]). DISCUSSION: MoCA has reasonable accuracy for poststroke neurocognitive disorder diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02650531.

Methamphetamine Increases the Proportion of SIV-Infected Microglia/Macrophages, Alters Metabolic Pathways, and Elevates Cell Death Pathways: A Single-Cell Analysis.

Both substance use disorder and HIV infection continue to affect many individuals. Both have untoward effects on the brain, and the two conditions often co-exist. In the brain, macrophages and microglia are infectable by HIV, and these cells are also targets for the effects of drugs of abuse, such as the psychostimulant methamphetamine. To determine the interaction of HIV and methamphetamine, we isolated microglia and brain macrophages from SIV-infected rhesus monkeys that were treated with or without methamphetamine. Cells were subjected to single-cell RNA sequencing and results were analyzed by statistical and bioinformatic analysis. In the animals treated with methamphetamine, a significantly increased proportion of the microglia and/or macrophages were infected by SIV. In addition, gene encoding functions in cell death pathways were increased, and the brain-derived neurotropic factor pathway was inhibited. The gene expression patterns in infected cells did not cluster separately from uninfected cells, but clusters comprised of microglia and/or macrophages from methamphetamine-treated animals differed in neuroinflammatory and metabolic pathways from those comprised of cells from untreated animals. Methamphetamine increases CNS infection by SIV and has adverse effects on both infected and uninfected microglia and brain macrophages, highlighting the dual and interacting harms of HIV infection and drug abuse on the brain.

Neurocognitive Outcomes in a Cisternal Blood Injection Murine Model of Subarachnoid Hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) results in neurocognitive dysfunction and anxiety in humans and in animal models. Neurobehavioral tests such as the Morris Water Maze (MWM) and Elevated Plus Maze (EPM) tests are validated in several models of SAH but have not been tested in the murine cisternal blood injection SAH model. METHODS: Adult C57BL/6 mice (n=16) were randomized into two groups. Group 1 (n=8) received sham surgery. Group 2 (n=8) underwent SAH with 60 µL of autologous blood injected into the cisterna magna. Mice were then tested using the Modified Garcia Score on post-operative day 2 (POD2), EPM on POD5 & POD16, and MWM on POD6-16.Brain tissues harvested on POD16 were stained with Fluoro-Jade C to identify neurodegeneration in the hippocampus and cortex and Iba-1 immunofluorescence staining for microglial activation in the dentate gyrus and CA1 region of the hippocampus. RESULTS: SAH mice showed increased escape latency on POD10. Swim distance was significantly increased on POD9-10 and swim speed was significantly decreased on POD6&POD10 in SAH mice. SAH mice exhibited a trend for lowered proportion of covered arm entries in EPM on POD16. Modified Garcia Score was not significantly different between the groups on POD2. The area of microglial activation in the dentate gyrus and CA1 region of the hippocampus was mildly increased but not significantly different at day 16 after SAH. Similarly, no significant differences were noted in the number of Fluoro-Jade C (+) cells in cortex or hippocampus. CONCLUSIONS: Cisternal single blood injection in mice produces mild neurocognitive deficits most pronounced in spatial learning and most evident 10 days after SAH.

Perioperative neurocognitive dysfunction: thinking from the gut?

With the aging of the world population, and improvements in medical and health technologies, there are increasing numbers of elderly patients undergoing anaesthesia and surgery. Perioperative neurocognitive dysfunction has gradually attracted increasing attention from academics. Very recently, 6 well-known journals jointly recommended that the term perioperative neurocognitive dysfunction (defined according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition) should be adopted to improve the quality and consistency of academic communications. Perioperative neurocognitive dysfunction currently includes preoperatively diagnosed cognitive decline, postoperative delirium, delayed neurocognitive recovery, and postoperative cognitive dysfunction. Increasing evidence shows that the gut microbiota plays a pivotal role in neuropsychiatric diseases, and in central nervous system functions via the microbiota-gut-brain axis. We recently reported that abnormalities in the composition of the gut microbiota might underlie the mechanisms of postoperative cognitive dysfunction and postoperative delirium, suggesting a critical role for the gut microbiota in perioperative neurocognitive dysfunction. This article therefore reviewed recent findings on the linkage between the gut microbiota and the underlying mechanisms of perioperative neurocognitive dysfunction.

Optimizing cerebral oxygenation in cardiac surgery: A randomized controlled trial examining neurocognitive and perioperative outcomes.

OBJECTIVE: The study objective was to determine whether targeted therapy to optimize cerebral oxygenation is associated with improved neurocognitive and perioperative outcomes. METHODS: In a prospective trial, intraoperative cerebral oximetry monitoring using bilateral forehead probes was performed in cardiac surgical patients who were randomly assigned to an intervention group in which episodes of cerebral oxygen desaturation (<60% for >60 consecutive seconds at either probe) triggered an intervention protocol or a control group in which the cerebral oximetry data were hidden from the clinical team, and no intervention protocol was applied. Cognitive testing was performed preoperatively and at postoperative months 3 and 6; domains studied were response speed, processing speed, attention, and memory. Perioperative outcomes studied were death, hospital length of stay, intensive care unit length of stay, postoperative day of extubation, time on mechanical ventilation, intensive care unit delirium, Sequential Organ Failure Assessment on intensive care unit admission, and intensive care unit blood transfusion. RESULTS: Group mean memory change scores were significantly better in the intervention group at 6 months (0.60 [standard error, 0.30] vs -0.17 [standard error, 0.33], adjusted P = .008). However, presence, duration, and severity of cerebral desaturation were not associated with cognitive change scores. Perioperative outcomes did not differ between the intervention and control groups. CONCLUSIONS: Targeted therapy to optimize cerebral oxygenation was associated with better memory outcome in a group of cardiac surgical patients. Some aspects of the protocol other than desaturation duration and severity contributed to the observed neuroprotective effect.

Neurocognitive Changes After Carotid Revascularization According to Perfusion Parameters: A Meta-analysis of Current Literature.

BACKGROUND: Although the clinical outcomes continue to be scrutinized, there are a few data summarizing the changes in perfusion parameters in postoperative patients. The objective was to undertake a systematic literature review and perform a meta-analysis to assess the effects of cerebral perfusion changes in cognitive and functional status. METHODS: A systematic search was conducted in July 2018 identifying articles comparing perfusion parameter changes before and after carotid revascularization in patients with carotid artery stenosis. Combined overall effect sizes were calculated using random-effects models. RESULTS: The literature search identified 1031 unique articles eligible for analysis. Sixteen studies including 755 patients were identified. The studies were different for many methodological factors, for example, sample size, type of patients, statistical measure, type of test, timing of assessment, and so on. There were no differences in cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO2), and relative cerebral blood volume (rCBV) between preintervention and postintervention, but there was a significant increase of cerebral blood flow (CBF) (95% confidence interval [CI] standardized mean difference [Std. MD] : -0.83 [-1.27, -0.40]; P = 0.0002; I2 = 68%) and relative cerebral blood flow (rCBF) (95% CI Std. MD: -0.72 [-1.61, -0.27]; P < 0.0001; I2 = 48%) after operation. In addition, the perfusion of mean transit time (MTT) (95% CI Std. MD: 1.26 [0.62, 1.90]; P = 0.0001; I2 = 84%), oxygen extraction fraction (OEF) (95% CI Std. MD: 0.78 [0.24, 1.33]; P = 0.005; I2 = 0%), time to peak (TTP) (95% CI Std. MD: 0.46 [0.16, 0.77]; P = 0.003; I2 = 47%), and relative mean transit time (rMTT) (95% CI Std. MD: 0.41 [0.33, 0.50]; P < 0.00001; I2 = 67%) was higher before than after operation. CONCLUSIONS: The increase in changes in CBF and rCBF and the decrease in MTT, OEF, TTP, and rMTT after operation may indicate the improvement of cognition in the short term. Intraoperative perfusion parameters could be an important adjuvant monitoring method in neurocognitive changes after carotid revascularization.

Patient-Reported Neuropsychiatric Outcomes of Long-Term Survivors after Chimeric Antigen Receptor T Cell Therapy.

CD19-targeted chimeric antigen receptor (CAR) modified T cell immunotherapy is a novel treatment with promising results in patients with relapsed/refractory lymphoid malignancies. CAR T cell therapy has known early toxicities of cytokine release syndrome and neurotoxicity, but little is known about long-term neuropsychiatric adverse effects. We have used patient-reported outcomes, including Patient-Reported Outcomes Measurement Information System (PROMIS) measures, to assess neuropsychiatric and other patient-reported outcomes of 40 patients with relapse/refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, and acute lymphoblastic leukemia 1 to 5 years after treatment with CD19-targeted CAR T cells. Mean T scores of PROMIS domains of global mental health, global physical health, social function, anxiety, depression, fatigue, pain, and sleep disturbance were not clinically meaningfully different from the mean in the general US population. However, 19 patients (47.5%) reported at least 1 cognitive difficulty and/or clinically meaningful depression and/or anxiety, and 7 patients (17.5%) scored ≤40 in global mental health, indicating at least 1 standard deviation worse than the general population mean. Younger age was associated with worse long-term global mental health (P = .02), anxiety (P = .001), and depression (P= .01). Anxiety before CAR T cell therapy was associated with increased likelihood of anxiety after CAR T cell therapy (P = .001). Fifteen patients (37.5%) reported cognitive difficulties after CAR T cell therapy. Depression before CAR T cell therapy was statistically significantly associated with higher likelihood of self-reported post-CAR T cognitive difficulties (P = .02), and there was a trend for an association between acute neurotoxicity and self-reported post-CAR T cognitive difficulties (P = .08). Having more post-CAR T cognitive difficulties was associated with worse global mental health and global physical health. Our study demonstrates overall good neuropsychiatric outcomes in 40 long-term survivors after CAR T cell therapy. However, nearly 50% of patients in the cohort reported at least 1 clinically meaningful negative neuropsychiatric outcome (anxiety, depression, or cognitive difficulty), indicating that a significant number of patients would likely benefit from mental health services following CAR T cell therapy. Younger age, pre-CAR T anxiety or depression, and acute neurotoxicity may be risk factors for long-term neuropsychiatric problems in this patient population. Larger studies are needed to confirm these findings.

Health-related quality of life, emotional burden, and neurocognitive function in the first generation of metastatic melanoma survivors treated with pembrolizumab: a longitudinal pilot study.

PURPOSE: The aim of this study was to assess the evolution of health-related quality of Life (HRQoL), emotional burden, and neurocognitive function in the first-generation metastatic melanoma survivors treated with pembrolizumab. METHODS: Survivors were defined as patients who achieved a durable remission for at least 6 months after initiating pembrolizumab in a single-center observational study (N = 141). A semi-structured interview was performed at baseline. Neurocognitive computerized testing and patient-reported outcomes were collected at 4 time points to assess HRQoL using the EORTC QLQ-C30 and the HADS to assess anxiety and depression. RESULTS: Out of 35 eligible patients, 25 were recruited and completed baseline assessment (18 female; median age 58 years [range 28-86]; 24 completed the 1-year follow-up phase. Median time since diagnosis was 30 months (range 12-84); median time since initiation of pembrolizumab was 19 months (range 6-42). At all visits, survivors reported a significantly lower global HRQoL, lower physical, emotional, cognitive, role, and social functioning compared with the European Mean of the healthy population. Fifteen patients (64%) had clinical levels of anxiety/depression at one time point during follow-up. The clinical interview revealed that 12 patients (48%) suffered from Cancer-Related-Post-Traumatic-Stress disorder, of whom 7 (28%) developed transient suicidal ideation, 1 patient made a suicide attempt. Neurocognitive testing revealed cognitive impairment in 8 patients (32%). CONCLUSIONS: Metastatic melanoma survivors, treated successfully with pembrolizumab, are at risk for suffering from emotional distress and neurocognitive impairment with a persistent impact on their HRQOL. Timely detection in order to offer tailored care is indicated.

Benzodiazepine Use Is Associated With an Increased Risk of Neurocognitive Impairment in People Living With HIV.

OBJECTIVE: Despite potential for dependence and adverse neurological effects, long-term benzodiazepine (BZD) use is common among people living with HIV (PLWH). As PLWH are at risk for central nervous system dysfunction, we retrospectively examined the association between BZD use and HIV-associated neurocognitive impairment (NCI). METHODS: Three hundred six PLWH underwent comprehensive neurobehavioral evaluations. Current BZD use (BZD+) was determined through self-report. Using propensity scores, 153 BZD- individuals were matched to 153 BZD+ participants on demographics and medical comorbidities. Multiple regression models examined NCI and demographically adjusted neurocognitive T-scores as a function of BZD status, adjusting for estimated premorbid ability, current affective symptoms, and nadir CD4 count. Secondary analyses explored neurocognitive correlates of positive BZD urine toxicology screens (TOX+) and specific BZD agents. RESULTS: Median duration of BZD use was 24 months. Current BZD use related to higher likelihood of NCI (odds ratio = 2.13, P = 0.003) and poorer global (d = -0.28, P = 0.020), processing speed (d = -0.23, P = 0.047), and motor T-scores (d = -0.32, P = 0.008). Compared with BZD-/TOX-, BZD+/TOX+ exhibited additional decrements in executive function (d = -0.48, P = 0.013), working memory (d = -0.49, P = 0.011), and delayed recall (d = -0.41, P = 0.032). For individual agents, diazepam, lorazepam, and alprazolam were most strongly associated with NCI (odds ratios >2.31). DISCUSSION: BZD use may elevate risk for NCI in PLWH, potentially through diffuse neurocognitive slowing and acute compromise of recall and higher-order capacities. These effects are robust to psychosocial and HIV-specific factors and occur in comparison with a tightly matched BZD- group. Prospective and interventional studies should evaluate causal associations between NCI and BZD use and explore treatment alternatives to BZDs in PLWH.

Late effects of pediatric brain tumors.

PURPOSE OF REVIEW: Adverse late effects of pediatric brain tumors can be numerous and complex and potentially alter the life trajectories of survivors in a multitude of ways. We review these inter-related late effects that compromise neurocognitive function, general health, social and psychological adjustment, and overall adaptive and vocational outcomes, and threaten to undermine the ability of survivors to transition independently into adulthood and effectively manage their care. Intervention/prevention strategies and advances in treatment that may reduce such late effects are discussed. RECENT FINDINGS: Studies of neuropsychological late effects have revealed specific deficits in core cognitive functions of attention, working memory and processing speed, with many survivors demonstrating decline in working memory and processing speed over time, irrespective of tumor type or treatment. This in turn affects the ongoing development of higher order neurocognitive skills. Research also highlights the increasing burden of health-related, neuropsychological and psychosocial late effects into adulthood and impact across life outcomes. SUMMARY: Pediatric brain tumor survivors require coordinated interdisciplinary care, ongoing evaluation and management of late effects, and timely interventions focused on mitigating the impact of late effects. The transition to adulthood can be especially vulnerable and addressing barriers to care is of paramount importance.

Effect of hormonal changes on the neurological status in the menstrual cycle of patient with multiple sclerosis.

OBJECTIVES: Premenstrual worsening has been often complained by patients with multiple sclerosis (MS). However, there is no quantitative study in the literature regarding premenstrual worsening and there are only a few studies for its reasons. In diseases such as MS, which there are limited evidence about the etiology and the triggers, detection of the variables in menstrual period, which is defined relatively easy, has a great potential to shed light to the disease. In the present study, we aimed to detect whether there was a deterioration in premenstrual period of patients with MS and to measure the observed deterioration and the relationships between demographics, physical and hormonal variables. PATIENTS AND METHODS: This study included 44 patients with MS, who were diagnosed according to McDonald criteria, and 14 healthy controls. For two consecutive cycles, cases were evaluated on the basis of neurological functions in the premenstrual and ovulation phases. In each examination, blood samples were obtained for detection of the levels of sex hormones (FSH, LH, E2, Progesterone). In the first and the fourth examinations, we applied Multiple Sclerosis Functional Composite (MSFC). RESULTS: Patients with MS showed poor performance in all used measurements than the healthy controls. Premenstrual period was worse based on cognitive aspects than the ovulation period in both MS patients and healthy controls. This was more evident in patients with MS. Patients treated with immunomodulatory agents had better cognitive performance than those were not given these agents. CONCLUSION: In our study, the patients with MS were found to be worse in cognition, and physical performance when compared with the healthy group. In premenstrual period, cognitive functions, and physical performance deteriorated in patients with MS. Healthy people seemed to be deteriorated on cognition measured with Paced Auditory Serial Addition Test.

Pilot Study: Neurocognitive Disorders and Colonoscopy in Older Adults.

In a preoperative anesthesia setting with integrated neuropsychology for individuals >64 years of age, we completed a pilot study examining the association between neurocognitive disorders with frequency of missed colonoscopies and quality of bowel preparation (prep). Gastroenterologists completed the Boston Bowel Preparation Scale (BBPS) for each patient. Of 47 older adults seen in our service, 68% met criteria for neurocognitive disorders. All individuals failing to attend the colonoscopy procedure had met criteria for major neurocognitive disorder. Poor bowel prep was also identified in 100% of individuals with major neurocognitive disorder and 28% of individuals with mild neurocognitive disorder. Our pilot data suggest that, in high-risk individuals, the presence of neurocognitive disorders is risk factors for missed appointments and inadequate bowel prep. These pilot data provide reference statistics for future intervention protocols.

Evaluating Immunopathogenic Biomarkers During Severe Malaria Illness as Modifiers of the Neuropsychologic Benefits of Computer Cognitive Games Rehabilitation in Ugandan Children.

BACKGROUND: We explored 3 immunopathogenic biomarkers collected during acute malaria illness as potential moderators of gains from a computerized cognitive rehabilitation training (CCRT) intervention. METHOD: Von Willebrand Factor (vWF), tumor necrosis factor (TNF) and Regulated on Activation, Normal T Expressed and Secreted (RANTES) were assayed from plasma and cerebral spinal fluid (CSF) of children during acute severe malaria anemia or cerebral malaria. Two years after acute malaria illness, 150 surviving children and 150 nonmalaria community controls (CCs) from their households 6-12 years old entered a 3-arm randomized controlled trial of titrating and nontitrating CCRT against no CCRT. Tests of cognition [Kaufman Assessment Battery for Children (KABC)], Tests of Variables of Attention and Achenbach Child Behavior Checklist (CBCL) were administered before and after 24 CCRT sessions over a 3-month period, and at 1-year follow-up. Differences in outcomes by trial arms and biomarker levels were evaluated using linear mixed effects models. RESULTS: Severe malaria survivors with lower levels of vWF, lower CSF levels of TNF and higher levels of plasma and CSF RANTES had better KABC cognitive performance after both titrating and nontitrating CCRT compared with no CCRT. For the CBCL, high plasma RANTES was associated with no benefit from either the titrating and nontitrating CCRT, whereas high TNF plasma was predictive of the benefit for both interventions. These biomarker moderating effects were not evident for CC children. CONCLUSIONS: Severe malaria immunopathogenic biomarkers may be related to poorer long-term brain/behavior function as evidenced by diminished benefit from a computerized cognitive rehabilitation intervention.

Efficacy of a newly developed auditory-cognitive training system on speech recognition, central auditory processing and cognitive ability among older adults with normal cognition and with neurocognitive impairment.

AIM: To evaluate the efficacy of a newly developed auditory-cognitive training system on speech recognition, central auditory processing and cognition among older adults with normal cognition (NC) and with neurocognitive impairment (NCI). METHODS: A double-blind quasi-experiment was carried out on NC (n = 43) and NCI (n = 33) groups. Participants in each group were randomly assigned into treatment and control programs groups. The treatment group underwent auditory-cognitive training, whereas the control group was assigned to watch documentary videos, three times per week, for 8 consecutive weeks. Study outcomes that included Montreal Cognitive Assessment, Malay Hearing in Noise Test, Dichotic Digit Test, Gaps in Noise Test and Pitch Pattern Sequence Test were measured at 4-week intervals at baseline, and weeks 4, 8 and 12. RESULTS: Mixed design anova showed significant training effects in total Montreal Cognitive Assessment and Dichotic Digit Test in both groups, NC (P < 0.001) and NCI (P < 0.01). The NC group also showed significant training effects in the Malay Hearing in Noise Test (quiet) (P < 0.01), Gaps in Noise Test (P < 0.001) and Pitch Pattern Sequence Test (humming) (P < 0.05). All training effects were sustained up to 4 weeks after the training ended. CONCLUSIONS: The present study suggests that the newly developed auditory-cognitive training system has the potential to improve general cognition and some of the auditory processing abilities in both the NC and NCI groups. Because of the short test-retest intervals used in the present study, it is possible that the training effects were influenced by learning effect and, therefore, should be considered cautiously. Geriatr Gerontol Int 2019; 19: 768-773.