Long-term Cognitive Performance Research Articles

Reelin reverts biochemical, physiological and cognitive alterations in mouse models of Tauopathy

Reelin is an extracellular protein crucial for adult brain plasticity. Moreover, Reelin is protective against amyloid-β (Aβ) pathology in Alzheimer’s Disease (AD), reducing plaque deposition, synaptic loss and cognitive decline. Given that Tau protein plays a key role in AD pathogenesis, and that the Reelin pathway modulates Tau phosphorylation, here we explored the involvement of Reelin in AD-related Tau pathology. We found that Reelin overexpression modulates the levels of Tau phosphorylation in AD-related epitopes in VLW mice expressing human mutant Tau. in vitro, Reelin reduced the Aβ-induced missorting of axonal Tau and neurofilament proteins to dendrites. Reelin also reverted in vivo the toxic somatodendritic localization of phosphorylated Tau. Finally, overexpression of Reelin in VLW mice improved long-term potentiation and long-term memory cognitive performance thus masking the cognitive and physiological deficits in VLW mice. These data suggest that the Reelin pathway, which is also protective against Aβ pathology, modulates fundamental traits of Tau pathology, strengthening the potential of Reelin as a therapeutic target in AD.

Memory Performance Correlates of Hippocampal Subfield Volume in Mild Cognitive Impairment Subtype

The increased understanding that neuropathology begins decades before symptom onset, has led to the conceptualization and widespread utilization of Mild Cognitive Impairment (MCI) as an important transitional state between healthy aging and dementia. Further subcategorization to MCI subtype has led to more distinct prognoses and it is widely considered that amnestic and non-amnestic MCI (aMCI, naMCI) likely have distinct pathophysiologies. Yet, accurately classification remains contentious. Here, we differentiate hippocampal subfield volume between subtypes, diagnosed according to stringent clinical consensus criteria, where aMCI is characterized based on deficits in delayed recall (rather than encoding). We then identify memory performance correlates to subfield volume and associations with long-term cognitive performance and outcome. 3D T1-weighted structural MRI was acquired in 142 participants recruited from the Healthy Brain Aging (HBA) Clinic and diagnosed with aMCI (n = 38), naMCI (n = 84) or subjective memory complaints (SMC; n = 20). T1-weighted datasets were processed with the cortical and hippocampal subfield processing streams in FreeSurfer (v6.0). Subfield volumes, and associations with baseline and longitudinal objective memory scores were then examined. Subfield volumes were found to differentiate clinical profiles: subiculum, CA1, CA4 and dentate gyrus volumes were significantly reduced in aMCI compared to both naMCI and SMC. CA1 subfield volume was shown to predict concurrent memory performance in aMCI, while dentate gyrus volume significantly predicted longitudinal verbal learning and memory decline in the entire cohort. Our findings demonstrate that using a more stringent diagnostic approach to characterizing aMCI is well justified, as delayed recall deficits are strongly linked to underlying volumetric subfield reductions in CA1, CA4 and the dentate gyrus, subfields known to be associated with mnemonic processes. Further research is now warranted to replicate these findings in other MCI samples.

Frequency and risk factors associated with post-stroke dementia-an observational study on stroke patients without premorbid cognitive impairment

Longitudinal studies on cognitive outcomes after stroke revealed heterogeneous results and the underlying pathology and risk factors for so-called post-stroke dementia are unclear. To assess long-term cognitive performance changes in patients after the first ischemic stroke and to evaluate possible risk factors for post-stroke dementia. In this study 66 clinically mildly affected patients aged 54-87years without ahistory of dementia underwent extensive neuropsychological assessment after first ever ischemic stroke and again 6 months after the event (follow-up assessment). Demographic, clinical and paraclinical parameters were assessed as potential predictors for long-term cognitive outcome. At the group level significant performance improvements were found for most of the neurocognitive domains at the follow-up assessment. The greatest cognitive improvement was found in visuospatial processing. Immediately after stroke 54.5% of patients were considered cognitively impaired (z-scores < -2 in at least 2 neurocognitive domains). At follow-up only 16.7% were considered cognitively impaired according to this criterion and among these only 2 patients (3%) had developed anew, clinically relevant cognitive impairment (i.e. post-stroke dementia). Patients with inferior cognitive performance improvements at follow-up had on average larger brain lesions caused by the stroke as well as aprediabetic metabolic status. The probability of developing apost-stroke dementia syndrome is lower than previously assumed in patients with first ever stroke, with only mild clinical disability and without premorbid cognitive impairment. Long-term cognitive impairment could primarily be determined by the size of the lesioned brain area as well as the premorbid (pre)diabetic status.

The natural history of seizures and neuropsychiatric symptoms in childhood epilepsy with centrotemporal spikes (CECTS)

ObjectiveChildhood epilepsy with centrotemporal spikes (CECTS) (formally benign epilepsy with centrotemporal spikes, BECTS) is a common childhood epilepsy syndrome characterized by psychiatric, behavioral, and cognitive abnormalities and self-limited seizures. Although CECTS is one of the most well-characterized electroclinical epilepsy syndromes, the natural history of neuropsychiatric outcomes is poorly understood. We report the psychiatric, behavioral, and cognitive profiles over the course of disease from a large, prospectively-enrolled, longitudinal cohort of children with CECTS. We further characterize the detailed seizure course and test the relationship between several proposed risk factors and neuropsychiatric and seizure outcomes in these children. MethodsPatients diagnosed with CECTS were enrolled as part of a community-based study and followed from diagnosis through disease resolution (16.0 ± 3.1 years, N = 60). Twenty sibling controls were also recruited. We report the natural history of premorbid neuropsychiatric concerns, postmorbid neuropsychiatric diagnoses, long-term neuropsychological performance, seizure course, antiseizure medication (ASM) treatment response, and the relationship between duration seizure-free and remission. Age at onset and premorbid neuropsychiatric concerns were tested as predictors of seizure count, epilepsy duration, postmorbid neuropsychiatric diagnoses, and long-term neuropsychological performance. Antiseizure medication treatment duration, seizure count, and epilepsy duration were tested as predictors of postmorbid neuropsychiatric diagnoses and long-term neuropsychological performance. ResultsChildren with CECTS had a high incidence of ADD/ADHD symptoms (18.3%) or learning difficulties (21.7%) before diagnosis. New or persistent ADHD (20%), mood disorders (23.6%), learning difficulties (14.5%), and behavioral disorders (7.3%) were common after CECTS diagnosis. At 9-year follow-up, performance on formal neuropsychological testing was comparable to population statistics and sibling controls. More than two-thirds of treated children experienced at least one seizure during treatment. Most children (61.7%) had entered terminal resolution after 12 months seizure-free. Among all children, for each month seizure-free, there was a 6–7% increase in the probability of achieving terminal remission (p < 1e-10). The presence of a premorbid neurodevelopmental concern predicted a longer epilepsy duration (p = 0.02), higher seizure count (p = 0.02), and a postmorbid psychiatric or neurodevelopmental diagnosis (p = 0.002). None of the tested features predicted long-term neuropsychological performance. SignificanceChildren are at high risk of neuropsychiatric symptoms along the course of the disease in CECTS, however, long-term cognitive performance is favorable. The majority of children had a seizure while being treated with ASMs, suggesting that CECTS is not as pharmacoresponsive as assumed or that treatment approaches are not optimized. Among treated and untreated children, future seizure-risk can be estimated from duration seizure-free. The presence of a premorbid neuropsychiatric concern predicted a more severe disease course in CECTS.

Long-Term Cognitive Performance of Retired Athletes with Sport-Related Concussion: A Systematic Review and Meta-Analysis.

Objective: The purpose of this systematic review is to quantitatively estimate (or invest) the impacts of sports-related concussions (SRCs) on cognitive performance among retired athletes more than 10 years after retirement. Methods: Six databases including (MEDLINE, Scopus, Web of Science, SPORTDiscus, CINAHL, and PsycArtilces) were employed to retrieve the related studies. Studies that evaluate the association between cognitive function and the SRC of retired athletes sustaining more than 10 years were included. Results: A total of 11 studies that included 792 participants (534 retired athletes with SRC) were identified. The results indicated that the retired athletes with SRCs, compared to the non-concussion group, had significant cognitive deficits in verbal memory (SMD = −0.29, 95% CI −0.59 to −0.02, I2 = 52.8%), delayed recall (SMD = −0.30, 95% CI –0.46 to 0.07, I2 = 27.9%), and attention (SMD = −0.33, 95% CI −0.59 to −0.06, I2 = 0%). Additionally, meta-regression demonstrated that the period of time between testing and the last concussion is significantly associated with reduced verbal memory (β = −0.03681, p = 0.03), and increasing age is significantly associated with the verbal memory (β = −0.03767, p = 0.01), immediate recall (β = −0.08684, p = 0.02), and delay recall (β = −0.07432, p = 0.02). Conclusion: The retired athletes who suffered from SRCs during their playing career had declined cognitive performance in partial domains (immediate recall, visuospatial ability, and reaction time) later in life.

Hypertension Editors' Picks Preeclampsia.

Hypertension Editors' Picks Preeclampsia.

A Functional Link Between Mental Representation in Long-Term Memory and Cognitive Performance in Working Memory.

Although there have been various attempts to identify the perceptual-cognitive mechanisms underlying the superior performance of skilled players over novices in sports, few studies have examined the relationship between mental representations and cognitive performance according to the skill levels of players. The purpose of this study was to investigate the functional link between mental representations in long-term memory and cognitive information processing ability in working memory by analyzing mental representation structure and cognitive performance according to skill level. Twenty male skilled and 25 male novice tennis players participated in this study. Structural dimensional analysis of mental representation was used to evaluate the mental representation structure of a tennis serve. In addition, cognition and movement chronometry was used to assess the cognitive performance of a tennis serve in working memory. Results of the representational analysis showed that the similarity of the skilled players to the standard representation structure was higher than that of novices. Furthermore, results in cognitive performance showed that the skilled players had a higher accuracy and shorter response time compared to the novices. Finally, a significant correlation between the adjusted Rand index and cognition movement chronometry accuracy was observed. Taken together, the mental representation structure and cognitive performance of the skilled players were superior to those of the novices, and mental representations were positively correlated with the accuracy of the cognitive information processing. These results imply that the degree of functional connection between working memory and long-term memory may be used as a perceptual-cognitive factor to explain improvement in performance.

Impact of Preeclampsia on Long-Term Cognitive Function.

Preeclampsia increases a woman's risk of stroke and leads to short-term cognitive complaints. Our objective was to assess the impact of preeclampsia on long-term cognitive performance. This is a retrospective cohort study using data from the Coronary Artery Risk Development in Young Adults cohort of healthy individuals (18-30 years) recruited from the general population in 3 cities in the United States, followed for 25 years (1985-2010). Psychomotor speed (Digit Symbol Substitution Test), executive function (Stroop Test), and memory (Rey Auditory Verbal Learning Test) were contrasted between women with and without preeclampsia using multivariate linear regression. We included 568 parous women (193 with preeclampsia and 375 with normotensive pregnancy) without baseline neurological disease or depression matched according to delivery period. Approximately 18 years after delivery, preeclamptic women scored significantly lower on Digit Symbol Substitution Test than women with normotensive pregnancy (73.21±14.79 versus 75.87±15.22; P=0.047) and on the third trial of Stroop Test (correct answers: 38.85±3.62 versus 39.42±1.87; P=0.014; completion time: 44.02±10.48 versus 41.62±10.61 seconds; P=0.01), but there were no differences in Rey Auditory Verbal Learning Test. These differences were attenuated after adjustment for age, body mass index, hypertension, education, and depression. Similar differences in neurocognitive scores were noted between women with other hypertensive disorders of pregnancy and normotensive pregnancy. Hypertension in pregnancy does not seem to be independently associated with neurocognitive impairment later in life.

Acute Complement Inhibition Potentiates Neurorehabilitation and Enhances tPA-Mediated Neuroprotection.

Because complement activation in the subacute or chronic phase after stroke was recently shown to stimulate neural plasticity, we investigated how complement activation and complement inhibition in the acute phase after murine stroke interacts with subsequent rehabilitation therapy to modulate neuroinflammation and neural remodeling. We additionally investigated how complement and complement inhibition interacts with tissue plasminogen activator (tPA), the other standard of care therapy for stroke, and a U.S. Food and Drug Administration preclinical requirement for translation of an experimental stroke therapy. CR2fH, an injury site-targeted inhibitor of the alternative complement pathway, significantly reduced infarct volume, hemorrhagic transformation, and mortality and significantly improved long-term motor and cognitive performance when administered 1.5 or 24 h after middle cerebral artery occlusion. CR2fH interrupted a poststroke inflammatory process and significantly reduced inflammatory cytokine release, microglial activation, and astrocytosis. Rehabilitation alone showed mild anti-inflammatory effects, including reduced complement activation, but only improved cognitive recovery. CR2fH combined with rehabilitation significantly potentiated cognitive and motor recovery compared with either intervention alone and was associated with higher growth factor release and enhanced rehabilitation-induced neuroblast migration and axonal remodeling. Similar outcomes were seen in adult, aged, and female mice. Using a microembolic model, CR2fH administered in combination with acute tPA therapy improved overall survival and enhanced the neuroprotective effects of tPA, extending the treatment window for tPA therapy. A human counterpart of CR2fH has been shown to be safe and nonimmunogenic in humans and we have demonstrated robust deposition of C3d, the CR2fH targeting epitope, in ischemic human brains after stroke.SIGNIFICANCE STATEMENT Complement inhibition is a potential therapeutic approach for stroke, but it is not known how complement inhibition would interact with current standards of care. We show that, after murine ischemic stroke, rehabilitation alone induced mild anti-inflammatory effects and improved cognitive, but not motor recovery. However, brain-targeted and specific inhibition of the alternative complement pathway, when combined with rehabilitation, significantly potentiated cognitive and motor recovery compared with either intervention alone via mechanisms involving neuroregeneration and enhanced brain remodeling. Further, inhibiting the alternative pathway of complement significantly enhanced the neuroprotective effects of thrombolytic therapy and markedly expanded the therapeutic window for thrombolytic therapy.

Predicting Long-term Cognitive Dysfunction in Survivors of Critical Illness with Plasma Inflammatory Markers: a Retrospective Cohort Study.

Persistent inflammation in intensive care unit (ICU) survivors is associated with higher long-term mortality and poorer mobility. However, it is unknown if inflammatory markers are associated with other dysfunctions observed in survivors of critical illness. Thus, it was investigated if plasma levels of interleukin (IL)-6 and IL-10 at hospital discharge were associated with long-term functional and cognitive performance after ICU discharge. Adult patients admitted for >48h to a 20-bed mixed ICU in a University Hospital had blood collected within 48h before hospital discharge to measure IL-6 and IL-10 levels. After a median time of 48months, cognitive status was determined by the Mini-Mental State Examination (MMSE), and functional status was determined by the Barthel Index. Patients at the higher 25th percentile of both IL-6 and IL-10 had a worse long-term cognitive performance, but not worse functional status, even when adjusted for confounders after long-term follow-up. In conclusion, elevated circulating IL-6 and IL-10 concentrations at hospital discharge were associated with long-term cognitive dysfunction in ICU survivors.

The influence of body mass on long-term cognitive performance of children treated for sleep-disordered breathing

BackgroundLong-term follow-up of children treated for sleep-disordered breathing (SDB) is limited, as the examination of factors potentially contributing to recovery is also limited. This study aimed to examine whether the recovery of neurocognitive function is achieved at four years post-adenotonsillectomy for SDB in children and whether body mass status influences the outcome. MethodsThis prospective longitudinal study of 3- to 12-year-old children recruited from an otolaryngology clinic compared cognitive performance, sleep, ventilation, and body mass before and at four years post-adenotonsillectomy in children with SDB and compared these parameters to those of untreated healthy controls during the same time points. ResultsChildren were categorised as normal-weight control (n = 33), normal-weight SDB (n = 18), or overweight/obese SDB (n = 11). Body mass did not significantly differ at four year follow-up compared to the baseline in any subgroup (p > 0.05), and groups were matched on the basis of age and gender. Despite improved sleep and nocturnal ventilation at four years post-adenotonsillectomy, little gain was observed in neurocognitive performance in either nonobese or overweight/obese children with SDB. Overweight/obese children with SDB displayed worse neurocognitive performance than all other children. ConclusionAdenotonsillectomy improves nocturnal ventilation and sleep quality but not neurocognitive performance in the long term. Excess body mass may place children with SDB at increased risk of neurocognitive performance deficits.

Age of onset of Cannabis use and cognitive function in first-episode non-affective psychosis patients: Outcome at three-year follow-up

BackgroundIn recent years, the effects of cannabis use on cognitive functions in patients with psychosis have been widely studied. Recently, special emphasis has been placed on the impact of age at the onset of consumption on cognition in these patients. Method349 patients with a first episode of non-affective psychosis were studied. Patients were classified as cannabis users and non-users. Users were divided, according to their age when they began using cannabis, into: early-onset (age < 16) and late-onset (age ≥ 16) users. Differences between groups at baseline were studied based on sociodemographic, clinical, and cognitive variables. The groups were longitudinally (3-year) compared on cognitive variables. ResultsOut of the 349 patients included in this study, 38.7% (N = 135) were cannabis users. Of them, 39.3% (N = 53) were early-onset and 60.7% (N = 82) were late-onset cannabis users. No baseline differences were found between the early-onset and late-onset groups on cognitive domains. Longitudinally, only patients who had withdrawn from cannabis use during follow-up showed a significant improvement in verbal memory. ConclusionOur results did not show differences between the early-onset group and the other two groups in long-term cognitive performance, even if they kept consuming cannabis during the first three years of disease progression. Further studies are needed to elucidate the true relationship between early-onset cannabis use and cognitive function in patients with a first episode of psychosis.

Cognitive, motor, behavioural and academic performances of children born preterm: a meta‐analysis and systematic review involving 64 061 children

Preterm birth may leave the brain vulnerable to dysfunction. Knowledge of future neurodevelopmental delay in children born with various degrees of prematurity is needed to inform practice and policy. To quantify the long-term cognitive, motor, behavioural and academic performance of children born with different degrees of prematurity compared with term-born children. PubMed and Embase were searched from January 1980 to December 2016 without language restrictions. Observational studies that reported neurodevelopmental outcomes from 2 years of age in children born preterm compared with a term-born cohort. We pooled individual estimates of standardised mean differences (SMD) and odds ratios (OR) with 95% confidence intervals using a random effects model. We included 74 studies (64 061 children). Preterm children had lower cognitive scores for FSIQ (SMD: -0.70; 95% CI: -0.73 to -0.66), PIQ (SMD: -0.67; 95% CI: -0.73 to -0.60) and VIQ (SMD: -0.53; 95% CI: -0.60 to -0.47). Lower scores for preterm children in motor skills, behaviour, reading, mathematics and spelling were observed at primary school age, and this persisted to secondary school age, except for mathematics. Gestational age at birth accounted for 38-48% of the observed IQ variance. ADHD was diagnosed twice as often in preterm children (OR: 1.6; 95% CI: 1.3-1.8), with a differential effect observed according to the severity of prematurity (I2 = 49.4%, P = 0.03). Prematurity of any degree affects the cognitive performance of children born preterm. The poor neurodevelopment persists at various ages of follow up. Parents, educators, healthcare professionals and policy makers need to take into account the additional academic, emotional and behavioural needs of these children. Adverse effect of preterm birth on a child's neurodevelopment persists up to adulthood.

Association between Long-Term Slow-Wave Sleep Enhancement and Cognitive Performance (P6.073)

Association between Long-Term Slow-Wave Sleep Enhancement and Cognitive Performance (P6.073)

Memory performance-related dynamic brain connectivity indicates pathological burden and genetic risk for Alzheimer\u2019s disease

BackgroundThe incidence of Alzheimer’s disease (AD) strongly relates to advanced age and progressive deposition of cerebral amyloid-beta (Aβ), hyperphosphorylated tau, and iron. The purpose of this study was to investigate the relationship between cerebral dynamic functional connectivity and variability of long-term cognitive performance in healthy, elderly subjects, allowing for local pathology and genetic risk.MethodsThirty seven participants (mean (SD) age 74 (6.0) years, Mini-Mental State Examination 29.0 (1.2)) were dichotomized based on repeated neuropsychological test performance within 2 years. Cerebral Aβ was measured by 11C Pittsburgh Compound-B positron emission tomography, and iron by quantitative susceptibility mapping magnetic resonance imaging (MRI) at an ultra-high field strength of 7 Tesla (7T). Dynamic functional connectivity patterns were investigated by resting-state functional MRI at 7T and tested for interactive effects with genetic AD risk (apolipoprotein E (ApoE)-ε4 carrier status).ResultsA relationship between low episodic memory and a lower expression of anterior-posterior connectivity was seen (F(9,27) = 3.23, p < 0.008), moderated by ApoE-ε4 (F(9,27) = 2.22, p < 0.005). Inherent node-strength was related to local iron (F(5,30) = 13.2; p < 0.022).ConclusionOur data indicate that altered dynamic anterior-posterior brain connectivity is a characteristic of low memory performance in the subclinical range and genetic risk for AD in the elderly. As the observed altered brain network properties are associated with increased local iron, our findings may reflect secondary neuronal changes due to pathologic processes including oxidative stress.

Association of Anesthesia and Surgery During Childhood With Long-term Academic Performance

The results of preclinical studies suggest that anesthetic drugs administered to neonatal animals cause widespread neuronal apoptosis and later neurocognitive impairment. Adequately powered studies in the pediatric surgical population are scarce, and it is unclear whether such preclinical findings are relevant for the pediatric setting. To examine the association of anesthesia and surgery before age 4 years with long-term academic and cognitive performance indexed by school grades at age 16 years and IQ test scores at military conscription. This investigation was a cohort study among all children born in Sweden between January 1973 and December 1993. The dates of analysis were April 2013 to October 2015. Among all 2 174 073 Swedish children born between 1973 and 1993, we identified a primary study cohort of 33 514 children with 1 anesthesia and surgery exposure before age 4 years and no subsequent hospitalization and 159 619 matched unexposed control children. In addition, 3640 children with multiple surgical procedures before age 4 years were studied. Having at least 1 surgical procedure in the Swedish Patient Register before age 4 years. The mean school grades at age 16 years and IQ test scores at military conscription at age 18 years. The mean difference between the exposed cohort and unexposed cohort was estimated in a model that included sex, month of birth during the same year, gestational age at delivery, Apgar score at 5 minutes, maternal and paternal educational levels, annual taxable household income, cohabiting parents, and number of siblings. Among 33 514 exposed children (22 484 male and 11 030 female) and 159 619 unexposed children (105 812 male and 53 807 female) in the primary study cohort, 1 exposure before age 4 years was associated with a mean difference of 0.41% (95% CI, 0.12%-0.70%) lower school grades and 0.97% (95% CI, 0.15%-1.78%) lower IQ test scores. The magnitude of the difference was the same after multiple exposures. There was no difference in school grades with 1 exposure before ages 6 months, 7 to 12 months, 13 to 24 months, or 25 to 36 months. The overall difference was markedly less than the differences associated with sex, maternal educational level, or month of birth during the same year. Exposure to anesthesia and surgery before age 4 years has a small association with later academic performance or cognitive performance in adolescence on a population level. While more vulnerable subgroups of children may exist, the low overall difference in academic performance after childhood exposure to surgery is reassuring. These findings should be interpreted in light of potential adverse effects of postponing surgery.

Remote Lower White Matter Integrity Increases the Risk of Long-Term Cognitive Impairment After Ischemic Stroke in Young Adults.

Poststroke cognitive impairment occurs frequently in young patients with ischemic stroke (18 through 50 years of age). Accumulating data suggest that stroke is associated with lower white matter integrity remote from the stroke impact area, which might explain why some patients have good long-term cognitive outcome and others do not. Given the life expectancy of decades in young patients, we therefore investigated remote white matter in relation to long-term cognitive function. We included all consecutive first-ever ischemic stroke patients, left/right hemisphere, without recurrent stroke or transient ischemic attack during follow-up, aged 18 through 50 years, admitted to our university medical center between 1980 and 2010. One hundred seventeen patients underwent magnetic resonance imaging scanning including a T1-weighted scan, a diffusion tensor imaging scan, and completed a neuropsychological assessment. Patients were compared with a matched stroke-free control group (age, sex, and education matched). Cognitive impairment was defined as >1.5 SD below the mean cognitive index score of controls and no cognitive impairment as ≤1 SD. Tract-Based Spatial Statistics was used to assess the white matter integrity (fractional anisotropy and mean diffusivity). About 11 years after ischemic stroke, lower remote white matter integrity was associated with a worse long-term cognitive performance. A lower remote white matter integrity, even in the contralesional hemisphere, was observed in cognitively impaired patients (n=25) compared with cognitively unimpaired patients (n=71). These findings indicate that although stroke has an acute onset, it might have long lasting effects on remote white matter integrity and thereby increases the risk of long-term cognitive impairment.

Food for Thought: The Neuroscience of Nutrition to Fuel Cognitive Performance

Lawyering is a marathon, not a sprint. Law students and lawyers have the power to improve long-term cognitive performance with neuro-intelligence, the knowledge of how to enhance brain function. Almost nothing is more personal than the decision lawyers make about what to eat for breakfast, lunch, and dinner. In a two-year study examining the health of lawyers, Sharon McDowell-Larsen Ph.D., discovered that while 92% of the participants understood that eating habits have health impacts, half reported they consumed unhealthy diets. None of these lawyers were vegetarians or vegans, 58% consumed meat on a daily basis, and 64% wanted more health and wellness support from their law firms. Some law firms and law schools are cultivating wellness cultures, but little work has been done in the area of improving lawyer and law student nutrition.As a lawyer ages, her physical and mental health tend to deteriorate. Researchers use neuroimaging to examine the structural and functional integrity of the brain to identify conditions and practices that help or harm the brain. U.S. Government anti-aging lifestyle research recommends lawyers should: strive to exercise daily; maintain healthy weight, cholesterol, blood pressure, and glucose levels; and adopt a nutritious diet. Research also indicates that the most powerful prescription for improving health, aging well, and reducing the risk of illness is consuming a healthful diet. This article aims to inspire nutritional choices that fuel the lawyer’s most valuable tool, her brain. Section II of this Article develops the neuro-intelligence of the law student, law professor, lawyer, and judge. It describes lawyer brain structure, and discusses how the emotional and thinking brains work together to facilitate cognition; response to emotions and stress; and motivation, reward, and habit building. Section III explains neuroscience research on aging and neurodegenerative diseases such as Mild Cognitive Impairment, dementia, and Alzheimer’s disease. It examines the brain impact of physical conditions (weight and obesity, blood sugar and glycation, inflammation, and oxidative stress) and emotional conditions (stress and depression). Section IV discusses how the brain and body use energy, and the impact of nutrients such as carbohydrates, proteins, fats, water, vitamins, and minerals. Section V addresses the influence of caffeine and alcohol on brain function. Section VI critiques Paleo, Mediterranean, and Whole-Food Plant-Based Diets according to their brain health strengths and weaknesses. The Article concludes with recommendations for optimizing the lawyer brain with neuro-protective nutrition practices that may influence lawyers and motivate them to rethink their food philosophy and redesign their wellbeing plan.

Improvement of Cognitive and Psychomotor Performance in Patients with Mild to Moderate Obstructive Sleep Apnea Treated with Mandibular Advancement Device: A Prospective 1-Year Study.

This study aimed to provide the evidence on effect of mandibular advancement device (MAD) therapy on long-term cognitive and psychomotor performance, excessive daytime sleepiness, and quality of life in patients with mild to moderate obstructive sleep apnea (OSA). A total of 15 patients with mild to moderate OSA were treated with MAD therapy and they were followed up after 3 mo and 1 y of therapy. The patients were tested on three different tests of cognitive and psychomotor performance using the computer-based system Complex Reactionmeter Drenovac (CRD-series) at baseline and at the time of follow-up, and the 36-Item Short Form Health Survey (SF-36) questionnaire and Epworth Sleepiness Scale were used to assess their quality of life and excessive daytime sleepiness, respectively. The mean apnea-hypopnea index (AHI) decreased significantly from 22.9 ± 5.9 events/h at baseline, to 9.7 ± 4.5 events/h after 1 y of MAD therapy (p < 0.001). There was significant improvement on all three CRD-series tests used after 1 y of MAD therapy, considering total test solving time (TTST) and minimal single task solving time (MinT), whereas total number of errors committed during the tests (TE) remained unchanged. Self-reported measures, excessive daytime sleepiness, and three domains of quality of life, social functioning, general health perception, and health change following MAD therapy showed significant improvements after 1 y of MAD therapy. This study demonstrates significant improvements in cognitive and psychomotor performance, particularly in the domain of perceptive abilities, convergent thinking (constructing and solving simple mathematical tasks) and psychomotor reaction times, excessive daytime sleepiness, and quality of life in patients with mild to moderate OSA following MAD therapy.

Isoflurane Is More Deleterious to Developing Brain Than Desflurane: The Role of the Akt/GSK3β Signaling Pathway.

Demand is increasing for safer inhalational anesthetics for use in pediatric anesthesia. In this regard, researchers have debated whether isoflurane is more toxic to the developing brain than desflurane. In the present study, we compared the effects of postnatal exposure to isoflurane with those of desflurane on long-term cognitive performance and investigated the role of the Akt/GSK3β signaling pathway. Postnatal day 6 (P6) mice were exposed to either isoflurane or desflurane, after which the phosphorylation levels of Akt/GSK3β and learning and memory were assessed at P8 or P31. The phosphorylation levels of Akt/GSK3β and learning and memory were examined after intervention with lithium. We found that isoflurane, but not desflurane, impaired spatial learning and memory at P31. Accompanied by behavioral change, only isoflurane decreased p-Akt (ser473) and p-GSK3β (ser9) expressions, which led to GSK3β overactivation. Lithium prevented GSK3β overactivation and alleviated isoflurane-induced cognitive deficits. These results suggest that isoflurane is more likely to induce developmental neurotoxicity than desflurane in context of multiple exposures and that the Akt/GSK3β signaling pathway partly participates in this process. GSK3β inhibition might be an effective way to protect against developmental neurotoxicity.