Lower Working Memory Performance Research Articles

Sex dimorphism controls dysbindin-related cognitive dysfunctions in mice and humans with the contribution of COMT.

Cognitive dysfunctions are core-enduring symptoms of schizophrenia, with important sex-related differences. Genetic variants of the DTBPN1 gene associated with reduced dysbindin-1 protein (Dys) expression negatively impact cognitive functions in schizophrenia through a functional epistatic interaction with Catechol-O-methyltransferase (COMT). Dys is involved in the trafficking of dopaminergic receptors, crucial for prefrontal cortex (PFC) signaling regulation. Moreover, dopamine signaling is modulated by estrogens via inhibition of COMT expression. We hypothesized a sex dimorphism in Dys-related cognitive functions dependent on COMT and estrogen levels. Our multidisciplinary approach combined behavioral-molecular findings on genetically modified mice, human postmortem Dys expression data, and in vivo fMRI during a working memory task performance. We found cognitive impairments in male mice related to genetic variants characterized by reduced Dys protein expression (pBonferroni = 0.0001), as well as in male humans through a COMT/Dys functional epistatic interaction involving PFC brain activity during working memory (t(23) = -3.21; pFDR = 0.004). Dorsolateral PFC activity was associated with lower working memory performance in males only (p = 0.04). Also, male humans showed decreased Dys expression in dorsolateral PFC during adulthood (pFDR = 0.05). Female Dys mice showed preserved cognitive performances with deficits only with a lack of estrogen tested in an ovariectomy model (pBonferroni = 0.0001), suggesting that genetic variants reducing Dys protein expression could probably become functional in females when the protective effect of estrogens is attenuated, i.e., during menopause. Overall, our results show the differential impact of functional variants of the DTBPN1 gene interacting with COMT on cognitive functions across sexes in mice and humans, underlying the importance of considering sex as a target for patient stratification and precision medicine in schizophrenia.

11 Social Determinants of Health in Pediatric Brain Tumor Survivors: Associations between Neighborhood Opportunity and Neurocognitive and Psychological Outcomes

Objective:A growing body of research demonstrates that social determinants of health (SDOH) are important predictors of neurocognitive and psychological outcomes in survivors of pediatric brain tumor (PBT). Existing research has focused primarily on individual level SDOH (e.g., family income, education, insurance status). Thus, more information is needed to understand community level factors which may contribute to health inequities in PBT survivors. This study aimed to examine the effects of specific aspects of neighborhood opportunity on cognitive and emotional/behavioral outcomes among PBT survivors.Participants and Methods:The sample included clinically-referred PBT survivors who completed a neuropsychological evaluation (N=199, Mage=11.63, SD= 4.63, 56.8% male, 71.8% White). Data included an age-appropriate Wechsler Scale and parent-report questionnaires (Behavior Rating Inventory of Executive Function, Child Behavior Checklist). Nationally-normed Child Opportunity Index (COI) scores were extracted for each participant from electronic medical records based on home address using Census tract geocoding. The COI measures neighborhood-level quality of environmental and social conditions that contribute to positive health. It includes three component scores assessing distinct aspects of opportunity, which include educational opportunity (e.g., educational quality, resources, and outcomes), health/environmental opportunity (e.g., access to healthy food, healthcare, and greenspace) and social/economic opportunity (e.g., income, employment, poverty). Stepwise linear regression models were examined to identify significant predictors of cognitive/psychological outcomes associated with PBT; the three COI indices were entered as predictors and retained in the model if they significantly contribute to variance in the outcome.Results:Lower educational opportunity was associated with lower processing speed performance (Wechsler Processing Speed Index: t = 2.47, p = 0.02) and increased parent-reported executive functioning problems (BRIEF GEC: t = -2.25, p = 0.03; BRIEF Working Memory: t = -2.45, p = 0.02) and externalizing problems (CBCL Externalizing: t = -2.19, p = 0.03). Lower social/economic opportunity was associated with lower working memory performance (Wechsler Working Memory Index: t = 2.63, p < 0.01) and increased parent-reported internalizing problems (CBCL Internalizing: t = -2.38, p = 0.02). Health/environmental opportunity did not emerge as a primary predictor of any of the examined cognitive/psychological outcomes. Exploratory analyses examining the impact of age on associations between COI and cognitive/psychological outcomes found a significant moderation effect of age on the relationship between educational opportunity and processing speed (t = 2.35, p = 0.02) such that this association was stronger at older ages. There were no other moderation effects by age.Conclusions:Consistent with a growing body of literature demonstrating the impact of social and environmental contexts to health outcomes, these results show inequities in neurocognitive and psychosocial outcomes in PBT survivors related to neighborhood-level SDOH. Examination of specific neighborhood factors highlight educational and social/economic factors as particularly important contributors to neurocognitive/psychological risk for survivors. The identification of these specific and potentially modifiable risk factors is crucial to inform individual-level problem-prevention following oncological treatment, as well as community-level policy and advocacy efforts.

Caffeinated Soda Intake in Children Is Associated with Neurobehavioral Risk Factors for Substance Misuse

Background and objectives Use of psychotropic substances in childhood has been associated with both impulsivity and other manifestations of poor executive function as well as escalation over time to use of progressively stronger substances. However, how this relationship may start in earlier childhood has not been well explored. Here, we investigated the neurobehavioral correlates of daily caffeinated soda consumption in preadolescent children and examined whether caffeinated soda intake is associated with a higher risk of subsequent alcohol initiation. Methods Using Adolescent Brain Cognitive Development study data (N = 2,092), we first investigated cross-sectional relationships between frequent caffeinated soda intake and well-known risk factors of substance misuse: impaired working memory, high impulsivity, and aberrant reward processing. We then examined whether caffeinated soda intake at baseline predicts more alcohol sipping at 12 months follow-up using a machine learning algorithm. Results Daily consumption of caffeinated soda was cross-sectionally associated with neurobehavioral risk factors for substance misuse such as higher impulsivity scores and lower working memory performance. Furthermore, caffeinated soda intake predicted a 2.04 times greater likelihood of alcohol sipping after 12 months, even after controlling for rates of baseline alcohol sipping rates. Conclusions These findings suggest that previous linkages between caffeine and substance use in adolescence also extend to younger initiation, and may stem from core neurocognitive features thought conducive to substance initiation.

Differences in Brain Functional Network Topology in High and Low Working Memory Performance

Nowadays the network approach in neuroscience provides a promising way of analyzing neurophysiological mechanisms that underlie psychological functions and is widely used to study working memory. To date, data obtained in neuroimaging studies links working memory with topological features of brain networks, such as increased connectivity between frontal, parietal, and temporal regions, as well as increased integration in brain networks as a whole. The present study examines the relationship between the topological characteristics of functional brain networks with the performance in the Sternberg item recognition paradigm based on electroencephalographic data. It is shown that the higher performance in Sternberg paradigm, implying a higher efficiency of the processes of encoding, storage, and retrieval of information from working memory, is associated with an increase in the integration of functional networks, expressed in differences in the clustering coefficient, participation coefficient, Wiener index and eigenvector centrality between the groups of high and low working memory task performance (p < .01). In addition, our data suggest the variability in the topological pattern of connectivity, which can be traced through changes in the magnitude of the standard deviation of the values of topological metrics during the task.

Variations in Theta/Beta Ratio and Cognitive Performance in Subpopulations of Subjects with ADHD Symptoms: Towards Neuropsychological Profiling for Patient Subgrouping.

ADHD is a neurodevelopmental disorder appearing in childhood but remaining in many cases in adults. There are both pharmacological and non-pharmacological approaches to treating ADHD, but they do not have the same efficacy in all subjects. Better knowledge of the neurophysiological basis of this disorder will allow for the design of more effective treatments. Studies performing qEEG analysis in children suggest the existence of subgroups of ADHD patients with different neurophysiological traits. There are fewer studies in adults, who might have undergone plastic changes allowing them to cope with ADHD symptoms along with brain maturation. Herein, we study cognitive performance and the theta/beta ratio in young adults with ADHD symptoms. We found that subjects with ADHD symptoms and low working memory performance (n = 30) present higher theta/beta ratios than controls (n = 40) at O2 and T6 in the eyes-closed condition, as well as a tendency toward a higher theta/beta ratio at O1 and Cz. Subjects with ADHD and high working memory performance (n = 50) do not differ from the controls in their theta/beta ratios at any derivation. Our results suggest that neuropsychological profiling could be useful for patient subgrouping. Further research will allow for the distinction of neuropsychological profiles and their neurophysiological correlates, leading to a better classification of ADHD subtypes, thus improving treatment selection.

Multidomain cognitive training increases physical activity in people with Parkinson's disease with mild cognitive impairment

IntroductionCognitive impairment in Parkinson's disease (PD), especially in patients with mild cognitive impairment (PD-MCI), coincides with less physical activity. Cognitive trainings (CT) have been found to promote laboratory environment-based movement. Knowledge about their effect in natural home-based environment, reflecting everyday function, is sparse. This explorative study investigated short-term effects of CT on physical activity assessed by home-based accelerometry, and its relation to change of cognitive function over time and non-cognitive outcomes in patients with PD-MCI. Cognitive and non-cognitive correlates of movement parameters at pretest were evaluated as well. MethodsEighteen patients with PD-MCI of the TrainParC study were analyzed. Those patients received either a 6-week multidomain group CT or physical training (PT). Physical activity and sedentary behavior were assessed with wearable accelerometers worn up to seven days pre- and post-training. ResultsPatients in the CT group displayed significantly greater increases in active periods after training than patients assigned to PT. In the CT group, increases in executive functioning were associated with increases in active periods and decreases in active mean bout length after training. At pretest, reduced working memory correlated with longer sedentary mean bout length, and impairment in activities of daily living (ADL) correlated with a higher number of sedentary periods. ConclusionStudy data revealed that CT can increase physical activity in patients with PD-MCI, possibly due to effects on executive functions, which needs further investigation in larger sample sizes. Lower working memory performance and ADL impairment might be associated with a more inactive lifestyle in patients with PD-MCI.

Working memory and reaction time variability mediate the relationship between polygenic risk and ADHD traits in a general population sample

Endophenotypes are heritable and quantifiable traits indexing genetic liability for a disorder. Here, we examined three potential endophenotypes, working memory function, response inhibition, and reaction time variability, for attention-deficit hyperactivity disorder (ADHD) measured as a dimensional latent trait in a large general population sample derived from the Adolescent Brain Cognitive DevelopmentSM Study. The genetic risk for ADHD was estimated using polygenic risk scores (PRS) whereas ADHD traits were quantified as a dimensional continuum using Bartlett factor score estimates, derived from Attention Problems items from the Child Behaviour Checklist and Effortful Control items from the Early Adolescent Temperament Questionnaire-Revised. The three candidate cognitive endophenotypes were quantified using task-based performance measures. Higher ADHD PRSs were associated with higher ADHD traits, as well as poorer working memory performance and increased reaction time variability. Lower working memory performance, poorer response inhibition, and increased reaction time variability were associated with more pronounced ADHD traits. Working memory and reaction time variability partially statistically mediated the relationship between ADHD PRS and ADHD traits, explaining 14% and 16% of the association, respectively. The mediation effect was specific to the genetic risk for ADHD and did not generalise to genetic risk for four other major psychiatric disorders. Together, these findings provide robust evidence from a large general population sample that working memory and reaction time variability can be considered endophenotypes for ADHD that mediate the relationship between ADHD PRS and ADHD traits.

Investigation of Working Memory Performances of Children with Low Early Mathematics Achievement

This study examined the working memory performance of children with low early mathematics achievement in comparison with their peers and analyzed the relationships between these skill areas. The distribution of children with low, average and high early mathematics achievement according to their working memory levels was also examined. The participants consisted of 100 kindergarten children with typical development and average and above-average intelligence. The Colored Progressive Matrices Test (CPM) was used to determine nonverbal intelligence levels, the Test of Early Mathematics Ability, Third Edition (TEMA-3) to evaluate early math skills and the Working Memory Scale (WMS) to determine working memory performances of the children. Children were divided into three groups of low, average and high achievement according to their early mathematics achievement assessed by the TEMA-3. It was found that the working memory performances of children with low, average and high achievement in early mathematics differed significantly. The working memory performance of children with low early mathematics achievement was significantly lower than their peers with average and high achievement. The results of the relationships between early math skills and working memory showed that early math skills and working memory components, except for visual short-term memory, were correlated to a small and medium degree. The distributions of working memory levels of the groups were examined and the results showed that children with low early mathematics achievement had low and average working memory performance, while children with high early mathematics achievement mostly had average and high working memory performance. However, none of the children with low early mathematics achievement showed high working memory performance. The results are discussed within the framework of the literature.

Do boys with MAOA_LPR*2R allele present cognitive and learning impairments?

ABSTRACT.Monoamine oxidase A (MAOA) polymorphisms have been associated with antisocial disorders. Less attention has been paid to the cognitive functioning of individuals with different MAOA alleles. No study has described the cognitive phenotype associated with the less frequent, low enzyme activity allele, MAOA_LPR*2R.Objective: We describe the cognitive correlates of boys having MAOA_LPR*2R allele, ascertained in a sample of school children with normal intelligence, not referred for behavioral disorders.Methods: Participants were eight boys, attending from the second to fifth grades in state-run schools. They were identified among 712 children with typical general cognitive ability, genotyped for MAOA_LPR polymorphism. Participants were assessed with general intelligence, mathematics and spelling achievement, and verbal and visuospatial working memory tests. Neuropsychological performance was compared to published standards, using 1 SD below the mean as a cutoff value for low performance.Results: Intelligence of boys with MAOA_LPR*2R allele varied from above average (N=2) to low average in the other children. Five out of eight boys with the MAOA_LPR*2R allele had low mathematics achievement, and three presented additional difficulties with spelling. Four out of eight children had low short-term and working memory performance.Discussion: This is the first study describing cognitive correlates and school performance in boys having the MAOA_LPR*2R allele. Having this allele, and therefore, probably low MAO-A activity, does not necessarily imply low intelligence or low school performance. However, learning difficulties, particularly in math, and low working memory performance were observed in boys having this allele. This suggests a role of MAOA in learning difficulties.

Cerebral blood flow and cognitive outcome after pediatric stroke in the middle cerebral artery

Adaptive recovery of cerebral perfusion after pediatric arterial ischemic stroke (AIS) is sought to be crucial for sustainable rehabilitation of cognitive functions. We therefore examined cerebral blood flow (CBF) in the chronic stage after stroke and its association with cognitive outcome in patients after pediatric AIS. This cross-sectional study investigated CBF and cognitive functions in 14 patients (age 13.5 ± 4.4 years) after pediatric AIS in the middle cerebral artery (time since AIS was at least 2 years prior to assessment) when compared with 36 healthy controls (aged 13.8 ± 4.3 years). Cognitive functions were assessed with neuropsychological tests, CBF was measured with arterial spin labeled imaging in the anterior, middle, and posterior cerebral artery (ACA, MCA, PCA). Patients had significantly lower IQ scores and poorer cognitive functions compared to healthy controls (p < 0.026) but mean performance was within the normal range in all cognitive domains. Arterial spin labeled imaging revealed significantly lower CBF in the ipsilesional MCA and PCA in patients compared to healthy controls. Further, we found significantly higher interhemispheric perfusion imbalance in the MCA in patients compared to controls. Higher interhemispheric perfusion imbalance in the MCA was significantly associated with lower working memory performance. Our findings revealed that even years after a pediatric stroke in the MCA, reduced ipsilesional cerebral blood flow occurs in the MCA and PCA and that interhemispheric imbalance is associated with cognitive performance. Thus, our data suggest that cerebral hypoperfusion might underlie some of the variability observed in long-term outcome after pediatric stroke.

Ambulatory assessment of rumination and worry: Capturing perseverative cognitions in children's daily life.

Rumination and worry are common forms of perseverative cognition in children. Research has started to target perseverative cognitions in the everyday life of children, however, valid measurement instruments reliably capturing rumination and worry in children's daily life are still missing. We conducted two ambulatory assessment studies validating short scales suitable for the measurement of rumination and worry in children's daily life. Results of the first study (N = 110, 8-11 year-olds, 31 days, up to 4 daily measurements) supported a unidimensional structure of the rumination scale. Rumination was associated with negative affect (but not positive affect) on the within- and on the between-person level. On the between-person level, children who ruminated more showed poorer working memory performance. In the second study (N = 84, 8-10 year-olds, 21 days, up to 3 daily measurements), findings of Study 1 were largely replicated. Moreover, we established a unidimensional worry scale in Study 2 reliably capturing worry in children's daily life. Importantly, Study 2 showed that worry and rumination share common variance but can be differentiated in children. On the within-person level, higher levels of worry were associated with higher levels of negative affect and lower levels of positive affect. On the between-person level, worry was associated with higher levels of negative affect and lower working memory performance. Altogether, findings of both studies demonstrated that the short scales had excellent psychometric properties suggesting that they are helpful tools for the assessment of rumination and worry in children's daily life.person level, worry was associated with higher levels of negative affect and lower working memory performance. Altogether, findings of both studies demonstrated that the short scales had excellent psychometric properties suggesting that they are helpful tools for the assessment of rumination and worry in children's daily life (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Development of cardiorespiratory fitness standards for working memory using receiver operating curves in 15-year-old adolescents

BackgroundWorking memory performance is associated with better academic achievements in children and adolescents, and it is positively related to CRF. However, what level of cardiorespiratory fitness (CRF) discriminates higher working memory performance is not known. The purpose of this study was to identify CRF thresholds linked to working memory in adolescents.MethodsData of 141 adolescents (53.2 % girls) were collected (14.9 years) from a cross-sectional study during the year 2019. CRF was assessed by the 20-m shuttle run test, and maximal oxygen uptake was calculated using the Mahar´s equation. Working memory was evaluated by the Corsi blocks test and performance was classified by percentiles. Receiver operating characteristic (ROC) curve analysis was used to identify CRF thresholds.ResultsThe ROC analysis indicated that CRF could be used to discriminate working memory in adolescents. CRF thresholds of ≥45.03 ml.kg− 1.min− 1for boys and ≥36.63 ml.kg− 1.min− 1for girls were found to be indicative of “normal” working memory performance.ConclusionsCRF could discriminate low and normal working memory performance in 14-16- year-old adolescents. These thresholds could allow for earlier identification and intervention of low working memory performance using CRF.

Association of working memory and elevated overnight urinary norepinephrine in patients with schizophrenia

IntroductionNorepinephrine has both central and peripheral origins and is known to influence cognitive processes in attention, learning, and working memory, but the research regarding the impact of norepinephrine on cognition in schizophrenia remains sparse, and mainly focuses on centrally regulated noradrenergic effects. This study examined the relationship between cumulative overnight norepinephrine levels in the urine and working memory in patients with schizophrenia and healthy controls. MethodsUrinary catecholamines were collected overnight in patients with schizophrenia (n = 75) and healthy controls (n = 33). Working memory was assessed using the digit sequencing task. ResultsPatients showed significantly higher average levels of overnight norepinephrine (t(103.10) = −3.16, p = 0.002) and reduced working memory performance (t(90) = 3.87, p = 0.001) compared with healthy individuals. There was a significant negative correlation between norepinephrine and working memory in patients (r = −0.38, p = 0.005), but not in controls (r = 0.08, p = 0.67). After controlling for age, sex, antipsychotic medications, and serotonin-norepinephrine reuptake inhibitor-based antidepressants, the correlation remained significant (r = −0.41, p = 0.004). ConclusionsHigh peripheral overnight levels of urinary norepinephrine are associated with lower working memory performance in patients with schizophrenia. These results parallel previous studies suggesting that high levels of central norepinephrine may result in working memory impairments. As norepinephrine rapidly breaks down and usually does not pass through the blood-brain barrier, the potential effect of peripheral cumulative norepinephrine on working memory is intriguing, and needs to be further investigated.

No Effects of Acute Psychosocial Stress on Working Memory in Older People With Type 2 Diabetes.

Type 2 diabetes (T2D) has been considered a public health threat due to its growing prevalence, particularly in the older population. It is important to know the effects of psychosocial stress and its potential consequences for some basic cognitive processes that are important in daily life. Currently, there is very little information about how people with T2D face acute psychosocial stressors, and even less about how their response affects working memory (WM), which is essential for their functionality and independence. Our aim was to characterize the response to an acute laboratory psychosocial stressor and its effects on WM in older people with T2D. Fifty participants with T2D from 52 to 77 years old were randomly assigned to a stress (12 men and 12 women) or control (12 men and 14 women) condition. Mood and physiological (cortisol, C, and salivary alpha-amylase, sAA) responses to tasks were measured. In addition, participants completed a WM test before and after the stress or control task. Our results showed that the TSST elicited higher negative affect and greater C and sAA responses than the control task. No significant differences in WM were observed depending on the exposure to stress or the control task. Finally, participants who showed higher C and sAA responses to the stressor had lower WM performance. Our results indicate that medically treated older adults with T2D show clear, typical mood and physiological responses to an acute psychosocial stressor. Finally, the lack of acute psychosocial stress effects on WM suggests that it could be related to aging and not to this disease, at least when T2D is adequately treated.

Polygenic risk for ADHD and ASD and their relation with cognitive measures in school children.

Attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are child-onset neurodevelopmental disorders frequently accompanied by cognitive difficulties. In the current study, we aim to examine the genetic overlap between ADHD and ASD and cognitive measures of working memory (WM) and attention performance among schoolchildren using a polygenic risk approach. A total of 1667 children from a population-based cohort aged 7-11 years with data available on genetics and cognition were included in the analyses. Polygenic risk scores (PRS) were calculated for ADHD and ASD using results from the largest GWAS to date (N = 55 374 and N = 46 351, respectively). The cognitive outcomes included verbal and numerical WM and the standard error of hit reaction time (HRTSE) as a measure of attention performance. These outcomes were repeatedly assessed over 1-year period using computerized version of the Attention Network Test and n-back task. Associations were estimated using linear mixed-effects models. Higher polygenic risk for ADHD was associated with lower WM performance at baseline time but not over time. These findings remained significant after adjusting by multiple testing and excluding individuals with an ADHD diagnosis but were limited to boys. PRS for ASD was only nominally associated with an increased improvement on verbal WM over time, although this association did not survive multiple testing correction. No associations were observed for HRTSE. Common genetic variants related to ADHD may contribute to worse WM performance among schoolchildren from the general population but not to the subsequent cognitive-developmental trajectory assessed over 1-year period.

Predictors of Working Memory Maintenance and Decline in Older Adults

The aging process is associated with the gradual decline of several cognitive functions, and working memory is particularly affected. Although the majority of older adults experience a deterioration of their working memory, some individuals maintain their working memory in older age, and some suffer an extreme deterioration of their working memory. The purpose of the present study was to identify, among a total of 120 potential predictors, those that significantly contributed to these two extreme outcomes in working memory. A sample of 588 healthy adults was examined with the n-back task in the spatial and verbal domains using a 2-back level of difficulty. Individuals were classified as working memory maintainers or decliners if their discrimination level in the two domains was superior to the 80th percentile or inferior to the 20th percentile, respectively. Logistic regression identified eight and six significant predictors of working memory maintenance and decline, respectively. High vocabulary scores and smoking more were significant predictors of working memory maintenance; however, in the opposite direction, these same variables predicted working memory decline. Several consumption habits that influenced cerebrovascular function were found in both models. Psychological traits and everyday activities were present in both models. We identified specific predictors that contribute to extremely high or low working memory performance in older age.

Effects of Home-Based Working Memory Training on Visuo-Spatial Working Memory in Parkinson's Disease: A Randomized Controlled Trial.

Background:Cognitive impairment is a very frequent and severe nonmotor symptom of Parkinson’s disease (PD). Early intervention in this at-risk group for cognitive decline may be crucial for long-term preservation of cognitive functions. Computerized working memory training (WMT) has been proven beneficial in non-PD patient populations, but such evidence is still needed for patients with PD.Objective:This study aimed to evaluate the effect of WMT on visuo-spatial working memory (WM) in cognitively unimpaired patients with PD.Methods:A single-blind randomized controlled trial encompassing 76 patients with PD but no cognitive impairment according to level II diagnostic criteria was conducted. Thirty-seven patients engaged in home-based adaptive WMT 5 times per week for a period of 5 weeks, whereas the remaining patients were in the waiting list arm of the study (control group [CG]). Working memory performance was evaluated using a computerized task before and after intervention and at 14-week follow-up, allowing to quantify the precision of WM on a continuous scale, ie, to test not only if an item was remembered but also how well the location of this item was retained.Results:Coincidently, the WMT group showed slightly worse WM performance compared with the CG at baseline, which was ameliorated after WMT. This training-induced effect remained stable until follow-up.Conclusion:Patients showing relatively low WM performance, despite not formally diagnosable as Parkinson’s disease with mild cognitive impairment (PD-MCI), seem to benefit from home-based WMT. Thus, WMT could potentially be implemented in future trials as a time- and cost-efficient route to counteract subtle cognitive changes in early disease stages.Trial registration:German Clinical Trial Register (drks.de, DRKS00009379)

Acute neuroinflammation elicited by TLR-3 systemic activation combined with early life stress induces working memory impairments in male adolescent mice

Toll-like Receptors (TLRs) are implicated with the pathogenesis of cognitive impairment induced by inflammation. Early life stress is associated with altered trajectories of neuroimmune signaling with implications for cognitive development. However, effects of TLR-3 activation on early life stress-related cognitive outcomes are understudied. We investigated the effects of maternal separation (MS) during postnatal development and a viral immune challenge during adolescence on working memory performance. BALB/c mice exposed to MS were separated from their dams daily for 180-min from postnatal day (PND) 2 to 15. At PND 45, animals were challenged with a single i.p. injection of either Poly (I:C) or sterile saline, and then subjected to a spatial working memory test in a Y-maze apparatus. Gene expression was determined by qPCR. Protein levels of oxidative stress markers were also assessed. A single peripheral administration of a TLR-3 agonist was able to induce working memory impairments in adolescent mice exposed to MS. At a molecular level, exposure to MS was associated with lower mRNA levels of Tlr3 in the medial prefrontal cortex (mPFC). However, when MS animals were exposed to Poly (I:C), a more robust activation of Tlr3, Il6 and Nfkb1 gene transcription was observed in these mice compared with control animals. These modifications did not result in oxidative stress. Finally, higher mRNA levels of Nfkb1 in the mPFC were correlated with lower working memory performance, suggesting that altered NF-κB signaling might be related with poor cognitive functioning. These results have implications for how ELS affects neuroimmune signaling in the mPFC.

Stress effects on cognitive function in patients with major depressive disorder: Does childhood trauma play a role?

Impaired cognitive functioning constitutes an important symptom of major depressive disorder (MDD), potentially associated with elevated cortisol levels. Adverse childhood experiences (ACE) enhance the risk for MDD and can contribute to disturbances in the stress systems, including cortisol and cognitive functions. In healthy participants, cortisol administration as well as acute stress can affect cognitive performance. In the current study, we tested cognitive performance in MDD patients with (N = 32) and without (N = 52) ACE and healthy participants with (N = 22) and without (N = 37) ACE after psychosocial stress induction (Trier Social Stress Test, TSST) and a control condition (Placebo-TSST). MDD predicted lower performance in verbal learning and both selective and sustained attention, while ACE predicted lower performance in psychomotoric speed and working memory. There were no interaction effects of MDD and ACE. After stress, MDD patients were more likely to show lower performance in working memory as well as in selective and sustained attention compared with participants without MDD. Individuals with ACE were more likely to show lower performance in verbal memory after stress compared with individuals without ACE. Our results indicate negative effects of MDD and ACE on distinct cognitive domains. Furthermore, MDD and/or ACE seem to enhance susceptibility for stress-related cognitive impairments.

Working Memory and Inadequate Micronutrient Consumption in Healthy Seniors

Objective: To investigate whether inadequate intake of micronutrients, as defined by the Institute of Medicine’s (IOM) Recommended Dietary Allowance (RDA) according to gender, is associated with lower working memory performance in healthy seniors.Method: 601 female and 530 male seniors (≥60 years) in the National Health and Nutrition Examination Survey (NHANES) were included. Analyses of the association between RDA micronutrient reference levels and having a memory performance score in the lowest quartile were stratified by gender. Logistic regression was used to estimate unadjusted and adjusted odds ratios for having a memory performance score in the lowest quartile for individuals with inadequate RDA levels compared to adequate RDA levels.Results: Over half of participants had inadequate intake of vitamin C, choline, and zinc. Men who had less than the RDA of choline from their food were more likely to be in the lowest memory performance quartile, while women who with inadequate B2 were more likely to be in the lowest quartile.Discussion: Inadequate intake of micronutrients was significantly associated with lower working memory performance.