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Background: This study investigated the risk of diabetes by examining changes in memory, working memory, and processing speed among older adults to provide evidence on how each cognitive domain is associated with the risk of diabetes in older adults., Methods: This study used Health and Retirement Study data and tracked the respondents from 2012 to 2020 ( n  = 5,748). The Telephone Interview for Cognitive Status-27 includes three cognitive tests (recall, seven subtraction, and counting backward tests) to assess each cognitive domain. A Cox proportional hazard regression was used to calculate the changes in the odds ratio (OR) of diabetes by increasing each cognitive function and the parameter in covariates., Results: We found that the OR of diabetes decreased with increasing universal cognitive function, increasing memory, working memory, and processing speed, and that age increased the OR in all analysis models., Conclusion: The findings of this study contribute to filling gaps in the literature by exploring: (a) the association between each cognitive function and the decline in diabetes risk and (b) the varying patterns of change in diabetes risk with increasing cognitive function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Kim and An.)

Background: Moderate to severe traumatic brain injury (TBI) often results in cognitive deficits. Processing speed (PS) deficits are common, exerting a significant impact on daily life. Few studies have examined the efficacy of cognitive rehabilitation specifically for PS deficits in moderate to severe TBI., Objective: Examine the efficacy of Speed of Processing Training (SOPT) in moderate to severe TBI. This protocol is a 10-session behavioral intervention for PS deficits that has been successfully used with other cognitively impaired populations., Methods: This double-blind, placebo-controlled, randomized clinical trial included 46 participants with moderate to severe TBI, 22 randomly assigned to the treatment group and 24 to the placebo-control group. Baseline and follow-up measures included a task similar to the training task (UFOV), measures of near transfer (neuropsychological measures of processing speed: Symbol Digit Modalities Test (SDMT), Wechsler Adult Intelligence Scale-IV (WAIS-IV) Symbol Search, WAIS-IV Coding) and measures of far transfer [neuropsychological measures of learning and memory: the California Verbal Learning Test-II (CVLT-II), Memory Assessment Scales - Prose Memory (MAS-PM)]., Results: Significant improvement from pre-to post-SOPT was observed on all subtests of the UFOV, which is similar to the training task. There was no significant difference on neuropsychological measures of PS or new learning and memory post-treatment. Neuropsychological assessment 6-months post-treatment showed no significant change in PS ability over time. Monthly booster sessions did not impact performance at the 6-month follow-up., Conclusion: Consistent with the SOPT literature, SOPT improves PS ability as measured by the UFOV, a task similar to the training task, in moderate to severe TBI. However, neither near nor far transfer was noted. That is, no improvement was noted on neuropsychological measures of PS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chiaravalloti, Costa, Armknecht, Costanza, Wallace, Moore and DeLuca.)

Introduction: Individuals with multiple sclerosis (MS) frequently experience visual and oculomotor symptoms that may impact and confound neuropsychological assessments of information processing speed (IPS). In this study, we examined the effect of the psychostimulant methylphenidate on oculomotor function and the association between change in oculomotor speed and change in information processing speed., Methods: We used a repeated measures crossover design in which a sample of 11 participants with MS were randomly assigned to one of two treatment arms: one that received methylphenidate for 4 weeks and another that received a placebo for 4 weeks. After a 7-day washout period, the treatments were crossed over. The King Devick test, the Symbol Digit Modalities Test, and the Paced Auditory Serial Addition Test were administered at baseline and after each of the two study arms., Results: We found a significant improvement in oculomotor speed in the methylphenidate condition as compared to placebo. This improvement was significantly correlated with improvement on a visuomotor assessment of IPS (Symbol Digit Modalities Test), but no such association was found for an auditory-verbal assessment of IPS (Paced Auditory Serial Addition Test)., Discussion: These findings suggest that individuals with MS experience improved oculomotor speed while taking methylphenidate, which may, in turn, improve performance on assessments of IPS with visuomotor demands., Competing Interests: NC is on an advisory board for Akili Interactive and is a member of the editorial boards of Multiple Sclerosis Journal and Frontiers in NeuroTrauma. JD has received consulting fees/honorarium from Biogen, Sanofi Genzyme, Novartis, Roche, Celgene, and Bristol Myers Squibb. He has received grant funding from Biogen, Roche, Bristol Myers Squibb, and EMD Serono. He has participated on the advisory boards of Novartis, Janssen, and Bristol Myers Squibb. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rich, Alexander, Dobryakova, Chiaravalloti, DeLuca and Costa.)

Background: Due to the risk of cerebral vascular injury, children and adolescents with high-risk sickle cell disease (SCD) experience neurocognitive decline over time. Haploidentical stem cell transplantation (HISCT) from human leukocyte antigen-matched sibling donors may slow or stop progression of neurocognitive changes., Objectives: The study is to determine if HISCT can ameliorate SCD-associated neurocognitive changes and prevent neurocognitive progression, determine which specific areas of neurocognitive functioning are particularly vulnerable to SCD, and determine if there are age-related differences in neurocognitive functioning over time., Methods: We performed neurocognitive and neuroimaging in SCD recipients following HISCT. Children and adolescents with high-risk SCD who received parental HISCT utilizing CD34 + enrichment and mononuclear cell (T-cell) addback following myeloimmunoablative conditioning received cognitive evaluations and neuroimaging at three time points: pre-transplant, 1 and 2 years post-transplant., Results: Nineteen participants (13.1 ± 1.2 years [3.3-20.0]) received HISCT. At 2 years post-transplant, neuroimaging and cognitive function were stable. Regarding age-related differences pre-transplantation, older children (≥13 years) had already experienced significant decreases in language functioning ( p < 0.023), verbal intelligence quotient ( p < 0.05), non-verbal intelligence quotient ( p < 0.006), and processing speed ( p < 0.05), but normalized post-HISCT in all categories., Conclusion: Thus, HISCT has the potential to ameliorate SCD-associated neurocognitive changes and prevent neurocognitive progression. Further studies are required to determine if neurocognitive performance remains stable beyond 2 years post-HISCT. Clinical trial registration: The study was conducted under an investigator IND (14359) (MSC) and registered at clinicaltrials.gov (NCT01461837)., Competing Interests: MC has served as a consultant for Jazz Pharmaceuticals, Omeros Pharmaceuticals, Servier Pharmaceuticals, Abbvie and Novartis Pharmaceuticals; Speakers Bureau for Jazz Pharmaceuticals, Amgen, Inc., Sanofi and Sobi; Advisory Board for Astra Zeneca; and research funding from Celularity, Merck, Miltenyi Biotec, Servier, Omeros, Jazz Pharmaceuticals, and Janssen. Although not related to this study, RM has received travel related funding from Siemens Healthineers and Philips Healthcare. EV has received grant support and personal fees from ApoPharma, Inc., and personal fees from Global Blood Therapeutics, Inc., and UptoDate, not related to this study. This study was presented in part at the American Society for Transplantation and Cellular Therapy (ASTCT), Orlando, FL, February, 2020. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Braniecki, Vichinsky, Walters, Shenoy, Shi, Moore, Talano, Parsons, Flower, Panarella, Fabricatore, Morris, Mahanti, Milner, McKinstry, Duncan, van de Ven and Cairo.)

Introduction: There is a paucity of clinical studies examining the long-term effects of vagus nerve stimulation (VNS) on cognition, although a recent study of patients with drug-resistant epilepsy (DRE) treated with VNS therapy demonstrated significant improvement in executive functions as measured by the EpiTrack composite score. The present study aimed to investigate performance variability in three cognitive tests assessing executive functions and working memory in a cohort of DRE patients receiving VNS therapy during a follow-up duration of up to 5 years., Methods: The study included 46 DRE patients who were assessed with the Trail Making Test (TMT) (Parts A and B) and Digit Span Backward (DB) task prior to VNS implantation, 6 months and 12 months after implantation, and yearly thereafter as a part of the clinical VNS protocol. A linear mixed-effects (LME) model was used to analyze changes in test z scores over time, accounting for variations in follow-up duration when predicting changes over 5 years. Additionally, we conducted descriptive analyses to illustrate individual changes., Results: On average, TMT-A z scores improved by 0.024 units (95% confidence interval (CI): 0.006 to 0.042, p  = 0.009), TMT-B z scores by 0.034 units (95% CI: 0.012 to 0.057, p  = 0.003), and DB z scores by 0.019 units per month (95% CI: 0.011 to 0.028, p  < 0.001). Patients with psychiatric comorbidities achieved the greatest improvements in TMT-B and DB z scores among all groups (0.0058 units/month, p  = 0.036 and 0.028 units/month, p  = 0.003, respectively). TMT-A z scores improved the most in patients taking 1-2 ASMs as well as in patients with psychiatric comorbidities (0.042 units/month, p  = 0.002 and p  = 0.003, respectively)., Conclusion: Performance in all three tests improved at the group level during the follow-up period, with the most robust improvement observed in TMT-B, which requires inhibition control and set-switching in addition to the visuoperceptual processing speed that is crucial in TMT-A and working-memory performance that is essential in DB. Moreover, the improvement in TMT-B was further enhanced if the patient had psychiatric comorbidities., Competing Interests: NL has participated in a clinical trial for UCB; received speaker’s honoraria from LivaNova (OmaMedical). LK has received speaker’s honoraria from UCB, Merck, and Eisai; received support for travel to congress from UCB and Angelini Pharma. KL has received speaker’s honoraria from Medtronic. ER-O has received speaker’s honoraria from Novartis and Biogen. JP has participated in clinical trials for Eisai, UCB, and Bial; received research grants from Angelini Pharma, Eisai, Medtronic, UCB, and LivaNova; received speaker’s honoraria from LivaNova, Angelini Pharma, Eisai, Jazz Pharma, Medtronic, Orion Pharma, and UCB; received support for travel to congresses from LivaNova, Eisai, Medtronic, and UCB; and participated in advisory boards for LivaNova, Angelini Pharma, Jazz Pharma, Eisai, Medtronic, UCB, and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lähde, Basnyat, Raitanen, Kämppi, Lehtimäki, Rosti-Otajärvi and Peltola.)

Introduction: In this study we assessed the contribution of psychopathology, including the two domains of negative symptoms (motivational deficit and expressive deficit), processing speed as an index of neurocognition, and emotion recognition, as an index of social cognition, to poor functional outcomes in people with schizophrenia., Methods: The Positive and Negative Syndrome Scale was used to evaluate positive symptoms and disorganization and the Brief Negative Symptom Scale to assess negative symptoms. The Symbol Coding and the Trail Making Test A and B were used to rate processing speed and the Facial Emotion Identification Test to assess emotion recognition. Functional outcome was assessed with the Personal and Social Performance Scale (PSP). Regression analyses were performed to identify predictors of functional outcome. Mediation analyses was used to investigate whether social cognition and negative symptom domains fully or partially mediated the impact of processing speed on functional outcome., Results: One hundred and fifty subjects from 8 different European centers were recruited. Our data showed that the expressive deficit predicted global functioning and together with motivational deficit fully mediated the effects of neurocognition on it. Motivational deficit was a predictor of personal and social functioning and fully mediated neurocognitive impairment effects on the same outcome. Both motivational deficit and neurocognitive impairment predicted socially useful activities, and the emotion recognition domain of social cognition partially mediated the impact of neurocognitive deficits on this outcome., Conclusions: Our results indicate that pathways to functional outcomes are specific for different domains of real-life functioning and that negative symptoms and social cognition mediate the impact of neurocognitive deficits on different domains of functioning. Our results suggest that both negative symptoms and social cognition should be targeted by psychosocial interventions to enhance the functional impact of neurocognitive remediation., Competing Interests: GG has been a consultant for Angelini. AM has been a consultant and/or advisor to or has received honoraria from Angelini, Gedeon. Richter Bulgaria, Janssen Pharmaceuticals, Lundbeck, Otsuka Pharmaceutical, Pfizer, Pierre Fabre, Rovi. Pharma and Boehringer Ingelheim. AE received consulting fees and/or honoraria for speeches within the last 3 years from Angelini, AOP Orphan, Germania, Janssen, Krka, Lundbeck, Mylan, Neuraxpharm, Recordati, and Sandoz. BG has been the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research CINS January 2009 – December 2021, which was partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. She has no other conflicts to disclose. AH has been a consultant for Recordati and Boehringer Ingelheim and Newron Pharmaceuticals and participated in educational conferences for Janssen and Lundbeck. JH received consulting fees and/or honoraria for speeches within the last 3 years from Angelini, Lundbeck, Janssen and Servier. SG has been a consultant and/or advisor to or has received honoraria from Angelini, Boehringer Ingelheim, Gedeon Richter-Recordati, Innova Pharma-Recordati Group, Janssen, Lundbeck, Otsuka, Recordati Pharmaceuticals, Rovi Pharma and Sunovion Pharmaceuticals. GS is president of the Austrian Society of Neuropsychopharmacology and Biological Psychiatry, which is partially financed by the support from pharmaceutical companies. GS received consulting fees and/or honoraria for speeches within the last 3 years from Janssen, Lundbeck, Mylan, Recordati, and Schwabe. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CM declared a past co-authorship with the authors AM and SG to the handling editor. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Giordano, Pezzella, Mucci, Austin, Erfurth, Glenthøj, Hofer, Hubenak, Libiger, Melle, Nielsen, Rybakowski, Wojciak, Galderisi and Sachs.)

Introduction: We are developing the California Cognitive Assessment Battery (CCAB) to provide neuropsychological assessments to patients who lack test access due to cost, capacity, mobility, and transportation barriers., Methods: The CCAB consists of 15 non-verbal and 17 verbal subtests normed for telemedical assessment. The CCAB runs on calibrated tablet computers over cellular or Wi-Fi connections either in a laboratory or in participants' homes. Spoken instructions and verbal stimuli are delivered through headphones using naturalistic text-to-speech voices. Verbal responses are scored in real time and recorded and transcribed offline using consensus automatic speech recognition which combines the transcripts from seven commercial ASR engines to produce timestamped transcripts more accurate than those of any single ASR engine. The CCAB is designed for supervised self-administration using a web-browser application, the Examiner. The Examiner permits examiners to record observations, view subtest performance in real time, initiate video chats, and correct potential error conditions (e.g., training and performance failures, etc.,) for multiple participants concurrently., Results: Here we describe (1) CCAB usability with older (ages 50 to 89) participants; (2) CCAB psychometric properties based on normative data from 415 older participants; (3) Comparisons of the results of at-home vs. in-lab CCAB testing; (4) We also present preliminary analyses of the effects of COVID-19 infection on performance. Mean z-scores averaged over CCAB subtests showed impaired performance of COVID+ compared to COVID- participants after factoring out the contributions of Age, Education, and Gender (AEG). However, inter-cohort differences were no longer significant when performance was analyzed with a comprehensive model that factored out the influences of additional pre-existing demographic factors that distinguished COVID+ and COVID- cohorts (e.g., vocabulary, depression, race, etc.,). In contrast, unlike AEG scores, comprehensive scores correlated significantly with the severity of COVID infection. (5) Finally, we found that scoring models influenced the classification of individual participants with Mild Cognitive Impairment (MCI, z-scores < -1.50) where the comprehensive model accounted for more than twice as much variance as the AEG model and reduced racial bias in MCI classification., Discussion: The CCAB holds the promise of providing scalable laboratory-quality neurodiagnostic assessments to underserved urban, exurban, and rural populations., Competing Interests: DW, PP, TH, KH, MB, KG, and GW were employed by NeuroBehavioral Systems Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Woods, Pebler, Johnson, Herron, Hall, Blank, Geraci, Williams, Chok, Lwi, Curran, Schendel, Spinelli and Baldo.)

Previous studies evaluating the morphology of the selected retinal layers in schizophrenia showed abnormalities regarding macular thickness, retinal nerve fiber layer (RNLF), and ganglion cell complex (GCC). Concurrently, accumulating neuroimaging results suggest that structural alterations of the brain in this disease might be an effect of accelerated aging. Referring to these findings, we aimed to determine whether the thinning of the retinal layers assessed with the optic coherence tomography (OCT) in a group of schizophrenia patients ( n = 60) presents a significant age-related decrease exceeding potential changes noted in the control group ( n = 61). Samples of patients and controls were divided into three age subgroups, namely, younger, middle-aged, and older participants. OCT outcomes, such as macular thickness and volume, macular RNFL, peripapillary RNFL, and GCC, were analyzed concerning a diagnosis status (controls vs. patients) and age subgroups. Additionally, associations between retinal parameters, age, and selected cognitive functions were evaluated. post-hoc tests revealed that macular thickness and volume in patients undergo significant age-dependent thinning, which was not observed in the control group. Regression analyses confirmed the association between macular morphology and age. Selected speed-dependent cognitive functions in patients decreased significantly with age, and these features were also significantly associated with some OCT outcomes also after controlling for antipsychotic treatment. Our results suggest that reduced measures of retinal structure detected in schizophrenia may be an effect of accelerated aging; however, further research is needed using computational solutions derived from brain imaging studies based on large datasets covering representatives of all age groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Domagała, Domagała, Kopiś-Posiej, Harciarek and Krukow.)

Background: Cognitive dysfunction and brain atrophy are both common in progressive multiple sclerosis (MS) but are seldom examined comprehensively in clinical trials. Antioxidant treatment may affect the neurodegeneration characteristic of progressive MS and slow its symptomatic and radiographic correlates., Objectives: This study aims to evaluate cross-sectional associations between cognitive battery components of the Brief International Cognitive Assessment for Multiple Sclerosis with whole and segmented brain volumes and to determine if associations differ between secondary progressive (SPMS) and primary progressive (PPMS) MS subtypes., Design: The study was based on a baseline analysis from a multi-site randomized controlled trial of the antioxidant lipoic acid in veterans and other people with progressive MS (NCT03161028)., Methods: Cognitive batteries were conducted by trained research personnel. MRIs were processed at a central processing site for maximum harmonization. Semi-partial Pearson's adjustments evaluated associations between cognitive tests and MRI volumes. Regression analyses evaluated differences in association patterns between SPMS and PPMS cohorts., Results: Of the 114 participants, 70% had SPMS. Veterans with MS made up 26% ( n = 30) of the total sample and 73% had SPMS. Participants had a mean age of 59.2 and sd 8.5 years, and 54% of them were women, had a disease duration of 22.4 (sd 11.3) years, and had a median Expanded Disability Status Scale of 6.0 (with an interquartile range of 4.0-6.0, moderate disability). The Symbol Digit Modalities Test (processing speed) correlated with whole brain volume ( R = 0.29, p = 0.01) and total white matter volume ( R = 0.33, p < 0.01). Both the California Verbal Learning Test (verbal memory) and Brief Visuospatial Memory Test-Revised (visual memory) correlated with mean cortical thickness ( R = 0.27, p = 0.02 and R = 0.35, p < 0.01, respectively). Correlation patterns were similar in subgroup analyses., Conclusion: Brain volumes showed differing patterns of correlation across cognitive tasks in progressive MS. Similar results between SPMS and PPMS cohorts suggest combining progressive MS subtypes in studies involving cognition and brain atrophy in these populations. Longitudinal assessment will determine the therapeutic effects of lipoic acid on cognitive tasks, brain atrophy, and their associations., Competing Interests: AS contracted Research with Sanofi, Biogen, Novartis, Actelion, Genentech/Roche. Consulting fees from Octave Bioscience. Research support from Bristol Myers Squibb. Personal compensation for consulting for Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics and OctavemBioscience. Personal compensation non-promotional speaking for EMD Serono. Participationin ma Data Safety and Monitoring Board for NCT03073603, and NCT04877457. MF received a grant from Sanofi-Genzyme Canada. Honoraria or consultation fees from Alexion/Astra Zeneca, BiogenIdec, EMD Inc./EMD Serono/Merck Serono, Find Therapeutics, Hoffman La-Roche, Novartis, Quanterix, Sanofi-Genzyme, Teva Canada Innovation. Member of a company advisory board or board of directors for Alexion/Astra Zeneca, Atara Biotherapeutics, Bayer Healthcare, Celestra Health, EMD Inc./Merck Serono, Find Therapeutics, Hoffman La-Roche, Actelion/Janssen (J&J), Novartis, Sanofi-Genzyme, Setpoint Medical. Participation in a company sponsored speaker's bureau: Sanofi-Genzyme, EMD Serono. PR contracted research with Biogen, Genentech, Novartis, Sanofi. Consulting honoraria: Banner, BristolMyersSquibb, EMD Serono, Genentech, Novartis, Sanofi, TG therapeutics. Speaker honoraria: Biogen, BristolMyersSquibb, Genentech, Novartis, Sanofi, TG therapeutics. OS serves on the editorial boards of Therapeutic Advances in Neurological Disorders, has served on data monitoring committees for Genentech-Roche, Pfizer, Novartis, and TG Therapeutics without monetary compensation, has advised EMD Serono, Novartis, and VYNE, receives grant support from EMD Serono, is a 2021 recipient of a Grant for Multiple Sclerosis Innovation (GMSI), Merck KGaA, is funded by a Merit Review grant (federal award document number (FAIN) BX005664-01 from the United States (U.S.) Department of Veterans Affairs, Biomedical Laboratory Research and Development, is funded by RFA-2203-39314 (PI) and RFA-2203-39305 (co-PI) grants from the National Multiple Sclerosis Society (NMSS). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Spain, Hildebrand, Waslo, Rooney, Emmons, Schwartz, Freedman, Paz Soldan, Repovic, Solomon, Rinker, Wallin, Haselkorn, Stuve, Gross and Turner.)

Objective: Brain neuroplasticity in which sleep affects the speed of information processing in the elderly population has not been reported. Therefore, this study was conducted to explore the effects of sleep on information processing speed and its central plasticity mechanism in the elderly., Methods: A total of 50 individuals aged 60 and older were enrolled in this case control study. All subjects were divided into two groups according to the sleep time: short sleep duration (< 360 min) (6 men and 19 women; mean age: 66.96 ± 4.28 years old), and non-short sleep duration (> 360 min) (13 men and 12 women). Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated for each participant. Two-sample t -tests were performed to compare the ALFF, ReHo, and DC maps between the two groups. Then, the relationships among clinical features, fMRI and cognitive function were analyzed using general linear model., Results: Short sleep duration group showed significantly increased ALFF value in the bilateral middle frontal gyrus and right insula; significantly increased ReHo value in the left superior parietal gyrus, and decreased ReHo value in the right crebellum; significantly decreased DC value in the left inferior occipital gyrus, left superior parietal gyrus and right cerebellum ( p  < 0.05, AlphaSim correction). The ALFF value of right insula is significantly associated with symbol digit modalities test (SDMT) score ( β  = -0.363, p  = 0.033)., Conclusion: Short sleep duration and processing speed are significantly associated with remodeling spatial patterns of intrinsic brain activity in the elderly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pu, Zou, Wang, Lei, Zhao, Zeng and Yan.)

Objective: The aim of the present study was to assess the validity of the Ease of Language Understanding (ELU) model through a statistical assessment of the relationships among its main parameters: processing speed, phonology, working memory (WM), and dB Speech Noise Ratio (SNR) for a given Speech Recognition Threshold (SRT) in a sample of hearing aid users from the n200 database., Methods: Hearing aid users were assessed on several hearing and cognitive tests. Latent Structural Equation Models (SEMs) were applied to investigate the relationship between the main parameters of the ELU model while controlling for age and PTA. Several competing models were assessed., Results: Analyses indicated that a mediating SEM was the best fit for the data. The results showed that (i) phonology independently predicted speech recognition threshold in both easy and adverse listening conditions and (ii) WM was not predictive of dB SNR for a given SRT in the easier listening conditions (iii) processing speed was predictive of dB SNR for a given SRT mediated via WM in the more adverse conditions., Conclusion: The results were in line with the predictions of the ELU model: (i) phonology contributed to dB SNR for a given SRT in all listening conditions, (ii) WM is only invoked when listening conditions are adverse, (iii) better WM capacity aids the understanding of what has been said in adverse listening conditions, and finally (iv) the results highlight the importance and optimization of processing speed in conditions when listening conditions are adverse and WM is activated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Homman, Danielsson and Rönnberg.)

Background and Objectives: Cognitive difficulties in people with sickle cell anemia (SCA) are related to lower processing speed index (PSI) and working memory index (WMI). However, risk factors are poorly understood so preventative strategies have not been explored. Brain volumes, specifically white matter volumes (WMV) which increases through early adulthood, have been associated with better cognition in healthy typically developing individuals. In patients with SCA, the reduced WMV and total subcortical volumes noted could explain cognitive deficits. We therefore examined developmental trajectories for regional brain volumes and cognitive endpoints in patients with SCA., Methods: Data from two cohorts, the Sleep and Asthma Cohort and Prevention of Morbidity in SCA, were available. MRI data included T1-weighted axial images, pre-processed before regional volumes were extracted using Free-surfer. PSI and WMI from the Weschler scales of intelligence were used to test neurocognitive performance. Hemoglobin, oxygen saturation, hydroxyurea treatment and socioeconomic status from education deciles were available., Results: One hundred and twenty nine patients (66 male) and 50 controls (21 male) aged 8-64 years were included. Brain volumes did not significantly differ between patients and controls. Compared with controls, PSI and WMI were significantly lower in patients with SCA, predicted by increasing age and male sex, with lower hemoglobin in the model for PSI but no effect of hydroxyurea treatment. In male patients with SCA only, WMV, age and socioeconomic status predicted PSI, while total subcortical volumes predicted WMI. Age positively and significantly predicted WMV in the whole group (patients + controls). There was a trend for age to negatively predict PSI in the whole group. For total subcortical volume and WMI, age predicted decrease only in the patient group. Developmental trajectory analysis revealed that PSI only was significantly delayed in patients at 8 years of age; the rate of development for the cognitive and brain volume data did not differ significantly from controls., Discussion: Increasing age and male sex negatively impact cognition in SCA, with processing speed, also predicted by hemoglobin, delayed by mid childhood. Associations with brain volumes were seen in males with SCA. Brain endpoints, calibrated against large control datasets, should be considered for randomized treatment trials., Competing Interests: FK is a consultant for Global Blood Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hamdule, Kölbel, Stotesbury, Murdoch, Clayden, Sahota, Hood, Clark and Kirkham.)

Introduction: The present study explored age effects and the coupling of sensorimotor and cognitive functions in a stratified sample of 96 middle-aged and older adults (age 45-86 years) with no indication of mild cognitive decline. In our sensorimotor tasks, we had an emphasis on listening in noise and postural control, but we also assessed functional mobility and tactile sensitivity., Methods: Our cognitive measures comprised processing speed and assessments of core cognitive control processes (executive functions), notably inhibition, task switching, and working memory updating. We explored whether our measures of sensorimotor functioning mediated age differences in cognitive variables and compared their effect to processing speed. Subsequently, we examined whether individuals who had poorer (or better) than median cognitive performance for their age group also performed relatively poorer (or better) on sensorimotor tasks. Moreover, we examined whether the link between cognitive and sensorimotor functions becomes more pronounced in older age groups., Results: Except for tactile sensitivity, we observed substantial age-related differences in all sensorimotor and cognitive variables from middle age onward. Processing speed and functional mobility were reliable mediators of age in task switching and inhibitory control. Regarding coupling between sensorimotor and cognition, we observed that individuals with poor cognitive control do not necessarily have poor listening in noise skills or poor postural control., Discussion: As most conditions do not show an interdependency between sensorimotor and cognitive performance, other domain-specific factors that were not accounted for must also play a role. These need to be researched in order to gain a better understanding of how rehabilitation may impact cognitive functioning in aging persons., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van Wieringen, Van Wilderode, Van Humbeeck and Krampe.)

Children with autism spectrum disorder (ASD) show marked difficulties in reading comprehension, a complex cognitive skill fundamental to successful daily functioning that is associated with core executive functions. However, the neurophysiological mechanisms underlying reading comprehension deficits in these children remain elusive. Twenty-one right-handed males with high-functioning ASD (mean age = 10.24 years) and 23 age-, IQ-, educational level-, sex- and handedness-matched typically developing (TD; mean age = 10.14 years) individuals underwent a reading comprehension test and the semantic verbal fluency test that tapped core executive functions underlying reading comprehension during concurrent prefrontal functional near-infrared spectroscopy (fNIRS) measurement. Participants' information processing efficiency was also assessed. High-functioning ASD children exhibited general reading comprehension [main effect of group: F (1,40) = 7.58, p = 0.009], selective verbal fluency deficits [Group × category interaction: F = 0.032] and slower processing speed ( (1,42) = 4.90, p = 0.032] and slower processing speed ( t 42 = 2.36, p = 0.023). Regarding the hemodynamics of the prefrontal cortex (PFC), although ASD individuals showed comparable patterns of PFC brain activation to their healthy counterparts, lower PFC intrahemispheric [main effect of group: F (1,42) = 11.36, p < 0.001). Moreover, poorer semantic verbal fluency test performance was associated with slower information processing speed ( F (1,42) = 7.79, p = 0.008] functional connectivity were evident during the semantic verbal fluency test. At the whole-group level, poorer reading comprehension performance was associated with poorer performance in the semantic verbal fluency test ( r 42 = 0.508, p < 0.001). Moreover, poorer semantic verbal fluency test performance was associated with slower information processing speed ( r 42 = -0.312, p = 0.044), which is associated with reduced left medial PFC functional connectivity ( r 42 = -0.319, p = 0.040). Abnormal intrahemispheric and interhemispheric prefrontal hypoconnectivity is associated with deficits in executive processes essential for reading comprehension in ASD. Our study has provided important implications for the neuropsychological and neurophysiological mechanisms underlying reading comprehension deficits in ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chan, Chan, Yeung, Wang, Liu and Han.)

Background: Late-life depression (LLD) affects up to 18% of older adults and has been linked to elevated dementia risk. Mindfulness-based cognitive therapy (MBCT) holds promise for treating symptoms of depression and ameliorating cognitive deficits in older adults. While preliminary findings are promising, a definitive RCT investigating its effects on late life depression and cognition have not yet been conducted. We present a protocol describing a multi-site blinded randomized controlled trial, comparing the effects of MBCT and of an active control, a Health Enhancement Program (HEP), on depressive symptoms, executive functioning, and brain biomarkers of LLD, among several other exploratory outcomes., Methods: Two-hundred and thirteen ( n = 213) patients with LLD will be recruited at various centers in Montreal, QC, Canada. Participants will undergo stratified randomization to either MBCT or HEP intervention groups. We will assess changes in (1) depression severity using the Hamilton Depression Rating Scale (HAM-D17), (2) processing speed and executive functioning, (3) brain biomarkers of LLD (hippocampal volume, default network resting-state functional connectivity and executive network resting-state functional connectivity), and (4) other exploratory physiological and mood-based measures, at baseline (0 weeks), post intervention (8 weeks), and 26 weeks after baseline., Discussion: The proposed study will assess the clinical potential of MBCT to improve symptoms of depression, as well as examine its impact on cognitive impairments and neurobiological markers, and thus inform its use as a promising adjunct in the treatment of LLD., Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT05366088., Competing Interests: SR receives a salary award from the Fonds de Recherche de Québec Santé FRQS, is a consultant for AbbVie, and is a shareholder of Aifred Health. HS has a CIHR fellowship award, MITACS fellowship award, and AGE-WELL award. ZS is a cofounder of Mindful Noggin and receives royalties from Guilford Press. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bein, Lesage, Dikaios, Chakravarty, Segal, Royal, Speechley, Schiavetto, Blumberger, Sacchet, Therriault, Gruber, Tourjman, Richard-Devantoy, Nair, Bruneau, Rej, Lifshitz and Sekhon.)

Advanced aging is associated with cognitive decline. To decrease the healthcare system and socio-economic burdens as well as to promote better quality of life, is important to uncover the factors that may be related to the delay of cognitive impairments in older adults. This study investigated the relationship between physical activity levels, sedentary behavior and cardiorespiratory fitness with cognitive functioning in healthy older adults. Furthermore, it examined the mediating role of processing speed on the association between physical activity and executive functions and long-term memory. Thirty-two individuals aged between 63 and 77 years ( M = 68.16, SD = 3.73) underwent measurements of maximal oxygen uptake (VO 2 peak), 1-week of PA accelerometer measurement and a comprehensive cognitive assessment. Significant associations were observed between MVPA and cognitive processing speed. Equally, a significant positive indirect effect of MVPA on executive functioning and long-term memory was mediated by processing speed. Also, MVPA levels differentiated cognitive functioning in older adults - the physical active group outperformed the physical inactive group in processing speed, executive functions, and language abilities. Our results contribute to the literature on the MVPA levels as an important tool to promote healthier cognitive aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Silva-Fernandes, Cruz, Moreira, Pereira, Sousa, Sampaio and Carvalho.)

Background: Recent studies have reported that sulforaphane (SFN) intake with cognitive training had positive effects on cognitive functions. However, it is still unknown whether SFN intake alone has beneficial effects on cognition as well as mood. We investigated whether a SFN intake intervention improved cognitive performance and mood states in healthy older adults., Methods: In a 12-week, double-blinded, randomized controlled trial (RCT), we randomly assigned 144 older adults to a SFN group or a placebo group. We asked the participants to take a supplement (SFN or placebo) for 12 weeks. We measured several cognitive functions, mood states, and biomarkers before and after the intervention period., Results: The SFN group showed improvement in processing speed and a decrease in negative mood compared to the placebo group. In addition, the SFN group exhibited a higher SFN- N -acetyl-L-cysteine (NAC) level compared to the placebo group. However, there were no significant results in other biomarkers of oxidant stress, inflammation, or neural plasticity., Discussion: These results indicate that nutrition interventions using SFN can have positive effects on cognitive functioning and mood in healthy older adults., Competing Interests: QH, YU, and HS were full-time employees of KAGOME CO., LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nouchi, Hu, Ushida, Suganuma and Kawashima.)

Objective: Processing Speed (PS), the ability to perceive and react fast to stimuli in the environment, has been shown to be impaired in children with attention deficit hyperactivity disorder (ADHD). However, it is unclear whether PS can be improved following targeted treatments for ADHD. Here we examined potential changes in PS following application of transcranial electric stimulation (tES) combined with cognitive training (CT) in children with ADHD. Specifically, we examined changes in PS in the presence of different conditions of mental fatigue., Methods: We used a randomized double-blind active-controlled crossover study of 19 unmedicated children with ADHD. Participants received either anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (dlPFC) or transcranial random noise stimulation (tRNS), while completing CT, and the administration order was counterbalanced. PS was assessed before and after treatment using the MOXO-CPT, which measures PS in the presence of various conditions of mental fatigue and cognitive load., Results: tRNS combined with CT yielded larger improvements in PS compared to tDCS combined with CT, mainly under condition of increased mental fatigue. Further improvements in PS were also seen in a 1-week follow up testing., Conclusion: This study provides initial support for the efficacy of tRNS combined with CT in improving PS in the presence of mental fatigue in pediatric ADHD., Competing Interests: IB serves on the advisory board of Tech InnoSphere Engineering Ltd. RCK serves on the scientific advisory boards of Neuroelectrics Inc. and Tech InnoSphere Engineering Ltd. RCK filed a UK Patent via the University of Oxford for “Method for obtaining personalized parameters for transcranial stimulation, transcranial system, method of applying transcranial stimulation.” The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dakwar-Kawar, Berger, Barzilay, Grossman, Cohen Kadosh and Nahum.)

Aims: To examine the correlation between smoking status and different domains of cognitive function in elderly Americans., Methods: We used data from the 2011 to 2014 U.S. National Health and Nutrition Examination Survey (NHANES). Participants over 60 years with available smoking history and cognitive function data were enrolled in our analysis. The NHANES study included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) assessment, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST) to assess cognition. Multivariate regression analyses were used to estimate the association between cigarette smoking and cognitive function., Results: A total of 2,932 participants were enrolled in the analysis, including 372 (12.7%) current smokers, 1,115 (38%) former smokers, and 1,445 (49.3%) never smokers. Never smokers had in average 3.82 (95% CI, 2.21 to 5.43) points more than current smokers in the DSST, whereas former smokers had 3.12 (95% CI, 1.51 to 4.73) points more than current smokers. Besides, smoking was not associated with the results of the AFT or the CERAD test., Conclusions: This study suggests that cigarette smoking is associated with processing speed among the American elderly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zhang, Chen, Zhu, Zhou, Zhang, Dong and Cao.)

Introduction: Remission from major depressive disorder (MDD) is associated with residual symptoms related to reduced functioning, quality of life, and relapse risk. Previous studies have raised questions about mechanisms involved-in and affected by cognitive training. This study investigated the associations and changes among depressive symptoms, rumination, processing speed (PS), executive functioning (EF), and emotional working memory (e-WM) pre- post computerized working memory training (CWMT)., Method: Twenty-nine remitted participants were included in a pre- post pilot study of within-subject effects of online CWMT. A total of 20 participants completed the intervention and pre- post tests of EF and PS, e-WM, in addition to symptom and rumination measures. Associations between changes in symptoms and cognition were investigated pre- post. Associations between improvements in CWMT, depression history, and changes in cognition were explored. Hypotheses and statistics were preregistered before data were analyzed., Results: Manipulation of negatively valanced stimuli in e-WM showed an inverse association with rumination pre-intervention, but the association disappeared post-intervention. Cognitive functioning improved in most conditions with largest effects in EF. Symptoms did not change in the remitted sample. CWMT improvements were related to improvements in some aspects of EF and PS, but also to worse self-reported attention. Depression history was related to less improvement in EF., Limitations: Sample size was small and there was dropout from the study. There was no control group, thus precluding practice and placebo effects and causal relationships., Conclusions: Computerized WM training improves cognitive functions and could influence associations between e-WM and rumination. This could counteract functional impairment following MDD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ronold, Joormann and Hammar.)

Pediatric patients with sickle cell disease (SCD) experience a range of medical complications that result in significant morbidity and mortality. Recent advances in prophylactic and curative treatment approaches have highlighted the need for sensitive and clinically-meaningful trial endpoints. The detrimental effects of cognitive and psychological difficulties on social and economic mobility are well described. Although numerous reviews have assessed cognitive outcomes in other rare genetic disorders, SCD has not received the same focus. This review describes the cognitive (i.e., executive function and processing speed) and psychological domains (i.e., depression and anxiety) that are consistently associated with SCD pathology and, therefore, may be of particular interest as clinical trial endpoints. We then discuss corresponding well-validated and reliable cognitive tests and patient-reported outcomes (PROs) that may be appropriate for clinical trials given their robust psychometric properties, ease of administration, and previous use in the SCD population. Further, we provide a discussion of potential pitfalls and considerations to guide endpoint selection. In line with the move toward patient-centered medicine, we identify specific tests (e.g., NIH Toolbox Cognition Module, Wechsler Cancellation Test) and psychological PROs (e.g., PROMIS depression and anxiety scales) that are sensitive to SCD morbidity and have the potential to capture changes that are clinically meaningful in the context of patients' day to day lives. In particularly vulnerable cognitive domains, such as executive function, we highlight the advantages of composite over single-test scores within the context of trials. We also identify general (i.e., practice effects, disease heterogeneity) and SCD-specific considerations (i.e., genotype, treatment course, and disease course, including degree of neurologic, pain, and sleep morbidity) for trial measures. Executive function composites hold particular promise as trial endpoints that are clinically meaningful, amenable to change, relatively easy to collect, and can be incorporated into the routine care of patients with SCD in various settings and countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hood, Crosby, Stotesbury, Kölbel and Kirkham.)

Objective: Prior research has shown that ketamine has anti-suicide effects. Additional evidence also suggests that ketamine may offer pro-cognitive effects. Herein, we propose that the anti-suicide effects of ketamine are partially mediated via pro-cognitive effects. We aimed to determine whether improvement in cognitive function mediated change in suicidal ideation was associated with ketamine treatment., Methods: Unipolar or bipolar depressive patients ( n = 86) with suicidal ideation received six infusions of ketamine (0.5 mg/kg) over 2 weeks. The current severity of suicidal ideation and depression symptoms were assessed with the Beck Scale for Suicide Ideation (SSI) and the Montgomery-Asberg Depression Rating Scale (MADRS), respectively, at baseline, days 13 and 26. Cognitive domains, including processing speed, working memory, visual learning, and verbal learning were measured with the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery at the same time points., Results: Mediation analysis showed a significant total effect of ketamine treatment on SSI score (coef = -1.853, 95%CI [-2.2, -1.5]). The direct and total indirect (MADRS total score and any of cognitive domains) effects of ketamine on suicidal ideation both were statistically significant (direct: coef = -1.064 to -1.352; total indirect: coef = -0.501 to -0.788). MADRS total score and processing speed (but not other cognitive domains) were significant partial mediators of the association between ketamine treatment and improvements in suicidal ideation., Conclusion: Depressive symptoms severity and processing speed performance partially mediated improvements in suicidal ideation after repeated ketamine infusions in persons with unipolar or bipolar depressive disorder., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Wang, Lan, Li, Chao, Wu, McIntyre and Ning.)

Cognitive aging, especially cognitive control, and processing speed aging have been well-documented in the literature. Most of the evidence was reported based on cross-sectional data, in which inter-individual age effects were shown. However, there have been some studies pointing out the possibility of overlooking intra-individual changes in cognitive aging. To systematically examine whether age-related differences and age-related changes might yield distinctive patterns, this study directly compared cognitive control function and processing speed between different cohorts versus follow-up changes across the adult lifespan. Moreover, considering that cognitive aging has been attributed to brain disconnection in white matter (WM) integrity, this study focused on WM integrity via acquiring diffusion-weighted imaging data with an MRI instrument that are further fitted to a diffusion tensor model (i.e., DTI) to detect water diffusion directionality (i.e., fractional anisotropy, FA; mean diffusivity, MD; radial diffusivity, RD; axial diffusivity, AxD). Following data preprocessing, 114 participants remained for further analyses in which they completed the two follow-up sessions (with a range of 1-2 years) containing a series of neuropsychology instruments and computerized cognitive control tasks. The results show that many significant correlations between age and cognitive control functions originally shown on cross-sectional data no longer exist on the longitudinal data. The current longitudinal data show that MD, RD, and AxD (especially in the association fibers of anterior thalamic radiation) are more strongly correlated to follow-up aging processes, suggesting that axonal/myelin damage is a more robust phenomenon for observing intra-individual aging processes. Moreover, processing speed appears to be the most prominent cognitive function to reflect DTI-related age (cross-sectional) and aging (longitudinal) effects. Finally, converging the results from regression analyses and mediation models, MD, RD, and AxD appear to be the representative DTI measures to reveal age-related changes in processing speed. To conclude, the current results provide new insights to which indicator of WM integrity and which type of cognitive changes are most representative (i.e., potentially to be neuroimaging biomarkers) to reflect intra-individual cognitive aging processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hsieh and Yang.)

Negative and cognitive symptoms are core features of schizophrenia that are correlated in cross-sectional designs. To further explore the relationship between these critical symptom dimensions we use a method for stratifying participants based on level and persistence of negative symptoms from absent to sustained levels over a 10-year follow-up period. We investigate associations with cognitive performance and level of global functioning. First-episode psychosis (FEP) participants ( n = 102) and healthy controls ( n = 116) were assessed at baseline and follow-up. A cognitive battery consisting of 14 tests derived into four domains and a composite score were used in the analyses. FEP participants were stratified based on negative symptom items from the Positive and Negative Syndrome Scale (PANSS-R) into four groups with either no, mild, transitory or sustained symptoms over the 10-year follow-up period. Global functioning was measured with Global Assessment of Functioning Scale-Split version. Multivariate and univariate analyses of variance were used to explore between-group differences in level and course of cognitive performance as global functioning. A multivariate analysis with four cognitive domains as dependent variables, showed significant group differences in performance when including healthy controls and the negative symptom groups. The groups with no and mild negative symptoms outperformed the group with sustained levels of negative symptoms on verbal learning and memory. The group with no negative symptoms also outperformed the group with sustained negative symptoms on the cognitive composite score. Significant improvements on verbal learning and memory, executive functioning and the cognitive composite were detected for the entire sample. No differences in cognitive course were detected. There was a significant improvement in global functioning as measured by the GAF-F over the follow-up period ( p < 0.001), without any time x group interactions ( p = 0.25). Participants with sustained negative symptoms had a significantly lower level of global functioning at 10-year follow-up with an additional independent effect of the cognitive composite score, compared to all other groups. Individuals with an early illness course characterized by absence of negative symptoms form a group with better cognitive and functional outcomes than the impairments typically associated with schizophrenia. Individuals with sustained levels of negative symptoms on the other hand may require a combined focus on both negative and cognitive symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Engen, Vaskinn, Melle, Færden, Lyngstad, Flaaten, Widing, Wold, Åsbø, Haatveit, Simonsen and Ueland.)

Background: Eye movement parameters are often used during cognitive functioning assessments of patients with psychotic spectrum disorders. It is interesting to compare these oculomotor parameters with cognitive functions, as assessed using psychometric cognitive tests. A network analysis is preferable for understanding complex systems; therefore, the aim of this study was to determine the multidimensional relationships that exist between oculomotor reactions and neurocognition in patients with schizophrenia spectrum disorders. Materials and Methods: A total of 134 subjects (93 inpatients with schizophrenia spectrum disorders (ICD-10) and 41 healthy volunteers) participated in this study. Psychiatric symptom severity was assessed using the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the Young Mania Rating Scale. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale, and akathisia was assessed using the Barnes Akathisia Rating Scale. Eye movements were recorded using an eye-tracker SMI RED 500, and cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia. The statistical analyses were conducted using Minitab 17 Statistical Software, version 17.2.1. Data visualization and additional analyses were performed in the R 4.0.3 environment, using RStudio V 1.3.1093 software. Results: A network model of neurocognitive and oculomotor functions was constructed for the patients. In the full network (which includes all correlations) the median antisaccade latency value is the central element of the oculomotor domain, and the Symbol Coding test, the Digit Sequencing test, and the Verbal Fluency test are central elements in the neurocognitive domain. Additionally, there were connections between other cognitive and oculomotor functions, except for the antisaccade error latency in the oculomotor domain and the Token Motor Task in the neurocognitive domain. Conclusion: Network analysis provides measurable criteria for the assessment of neurophysiological and neurocognitive abnormalities in patients with schizophrenic spectrum disorders and allows to select key targets for their management and cognitive remediation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shmukler, Latanov, Karyakina, Anisimov, Churikova, Sukhachevsky and Spektor.)

Background: Suicide is moderately heritable and also more common in those who report childhood abuse. Previously, it was found that allele A of GABRG2 (GABA A receptor subunit gamma2) polymorphism rs211034 was protective in a suicide attempt (SA). Hence, it was proposed that rs211034 may interact with childhood trauma to influence cognitive deficits related to SA or depression risk. Genetic variants may predict the benefits of certain cognitive treatments. Methods: A total of 52 individuals who had attempted suicide, 59 individuals with major depressive disorder (MDD) or bipolar depression who had not previously attempted suicide, and 90 healthy volunteers were subjected to the modified Suicide Stroop task and were clinically assessed using the Childhood Trauma Questionnaire (CTQ) and Hamilton Depression Scale-24 items (HAMD-24). rs211034 was genotyped using Sanger sequencing. Results: After correcting for covariates, depressed participants displayed longer reaction times for all emotional conditions, including suicide-related words, compared with healthy controls. Depressed suicide attempters displayed longer reaction times for negative words than depressed non-attempters. Depressed non-attempters displayed higher interference scores for negative words compared with healthy controls. There was an interaction between rs211034 risk allele and the effects of reported childhood sexual abuse (CSA) on reaction time for all emotional words and suicide-related words. Carriers of the rs211034 risk allele A exhibited shorter reaction times, but the protective effects of this allele were eliminated in those exposed to reported CSA. Conclusion: Only limited results were found regarding effects of a past suicide attempt on response times to emotional and suicide-related words, but there was an overall effect of major depression on slower response time. Protective genetic effects of the rs211034 A allele on this slowing were eliminated in those with a history of sexual abuse during childhood. Further research is needed to better characterize the mechanisms underlying the effects of childhood trauma on these genetic effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yin, Guo, Xin, Zheng, Xue, Li, Liu, Yan, Keilp and Mann.)

Timing is an essential part of human cognition and of everyday life activities, such as walking or holding a conversation. Previous studies showed that traumatic brain injury (TBI) often affects cognitive functions such as processing speed and time-sensitive abilities, causing long-term sequelae as well as daily impairments. However, the existing evidence on timing capacities in TBI is mostly limited to perception and the processing of isolated intervals. It is therefore open whether the observed deficits extend to motor timing and to continuous dynamic tasks that more closely match daily life activities. The current study set out to answer these questions by assessing audio motor timing abilities and their relationship with cognitive functioning in a group of TBI patients ( n = 15) and healthy matched controls. We employed a comprehensive set of tasks aiming at testing timing abilities across perception and production and from single intervals to continuous auditory sequences. In line with previous research, we report functional impairments in TBI patients concerning cognitive processing speed and perceptual timing. Critically, these deficits extended to motor timing: The ability to adjust to tempo changes in an auditory pacing sequence was impaired in TBI patients, and this motor timing deficit covaried with measures of processing speed. These findings confirm previous evidence on perceptual and cognitive timing deficits resulting from TBI and provide first evidence for comparable deficits in motor behavior. This suggests basic co-occurring perceptual and motor timing impairments that may factor into a wide range of daily activities. Our results thus place TBI into the wider range of pathologies with well-documented timing deficits (such as Parkinson's disease) and encourage the search for novel timing-based therapeutic interventions (e.g., employing dynamic and/or musical stimuli) with high transfer potential to everyday life activities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Verga, Schwartze, Stapert, Winkens and Kotz.)

Objective: To strengthen future methodological choices regarding the measurement of cognition within the field of audiology, the current study aimed to examine the effect of, among other things, hearing sensitivity on the backward corsi tapping task (i.e., visual working memory and processing speed) and the letter-number sequencing task (i.e., verbal working memory and processing speed). Design and Study Sample: The backward corsi tapping task and the letter-number sequencing task were administered to 184 participants, aged between 18 and 69 years. The effect of age, sex, educational level, awakeness, and hearing sensitivity on verbal and visual working memory and processing speed was assessed using stepwise multiple regression analyses. Results: For all outcome variables, a decrease in performance was observed with increasing age. For visual and verbal working memory, males outperformed females, whereas no clear sex effect was observed for visual and verbal processing speed. Hearing sensitivity had only a significant impact on visual processing speed. Conclusion: The importance to evaluate cognitive construct validity within audiological research was highlighted. Further research should focus on investigating the associations between speech understanding on the one hand and the backward corsi tapping task and letter-number sequencing task on the other hand., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kestens, Degeest, Miatton and Keppler.)

Objectives: Myocyte Enhancer Factor 2C ( MEF2C ) is identified as a candidate gene contributing to the risk of developing Alzheimer's disease. However, little is known about whether MEF2C plays a role in specific aspects of cognition among older adults. The current study investigated the association of common variants in the MEF2C gene with four cognitive domains including memory, visuospatial functioning, processing speed and language among non-demented individuals., Method: Participants from two ethnic groups, Non-Hispanic White (NHW; n = 537) and Caribbean Hispanic (CH; n = 1,197) from the Washington Heights-Inwood Community Aging Project ( WHICAP) study, were included. Genetic association analyses using WHICAP imputed genome-wide data (GWAS) were conducted for the various cognition domains., Results: Single nucleotide polymorphisms (SNP) variants in the MEF2C gene showed nominally significant associations in all cognitive domains but for different SNPs across both the ethnic groups. In NHW participants, the strongest associations were present for memory (rs302484), language (rs619584), processing speed (rs13159808), and visuospatial functioning (several SNPs). In CH, strongest associations were observed for memory (rs34822815), processing speed (rs304141), visuospatial functioning (rs10066711 and rs10038371), and language (rs304153)., Discussion: MEF2C variant-cognitive associations shed light on an apparent role for MEF2C in both memory and non-memory aspects of cognition in individuals from NHW and CH ancestries. However, the little overlap in the specific SNP-cognition associations in CH versus NHW highlights the differences in genetic architectural variations among those from different ancestries that should be considered while studying the MEF2C gene., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sunderaraman, Cosentino, Schupf, Manly, Gu and Barral.)

Objective: Considerable evidence has shown that facial expression recognition ability and cognitive function are impaired in patients with depression. We aimed to investigate the relationship between facial expression recognition and cognitive function in patients with depression. Methods: A total of 51 participants (i.e., 31 patients with depression and 20 healthy control subjects) underwent facial expression recognition tests, measuring anger, fear, disgust, sadness, happiness, and surprise. The Chinese version of the MATRICS Consensus Cognitive Battery (MCCB), which assesses seven cognitive domains, was used. Results: When compared with a control group, there were differences in the recognition of the expressions of sadness ( p = 0.036), happiness ( p = 0.041), and disgust ( p = 0.030) in a depression group. In terms of cognitive function, the scores of patients with depression in the Trail Making Test (TMT; p < 0.001), symbol coding ( p < 0.001), spatial span ( p < 0.001), mazes ( p = 0.007), the Brief Visuospatial Memory Test (BVMT; p = 0.001), category fluency ( p = 0.029), and continuous performance test ( p = 0.001) were lower than those of the control group, and the difference was statistically significant. The accuracy of sadness and disgust expression recognition in patients with depression was significantly positively correlated with cognitive function scores. The deficits in sadness expression recognition were significantly correlated with the TMT ( p = 0.001, r = 0.561), symbol coding ( p = 0.001, r = 0.596), maze ( p = 0.015, r = 0.439), and the BVMT ( p = 0.044, r = 0.370). The deficits in disgust expression recognition were significantly correlated with impairments in the TMT ( p = 0.005, r = 0.501) and symbol coding ( p = 0.001, r = 0.560). Conclusion: Since cognitive function is impaired in patients with depression, the ability to recognize negative facial expressions declines, which is mainly reflected in processing speed, reasoning, problem-solving, and memory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ruihua, Hua, Meng, Nan, Panqi, Sijia, Jing, Yunlong, Shuping, Fude, Li and Zhiren.)

While executive functions (EFs) and self-regulated learning (SRL) strategy use have been found to be related in several populations, this relationship has not been studied in adult online distance education (ODE). This is surprising as self-regulation, and thus using such strategies, is very important here. In this setting, we studied the relation between basic executive functions (i.e., working memory and shifting, measured with cognitive tests) and reported SRL-strategy use (i.e., management of time and effort, complex and simple cognitive strategy use, contacts with others, and academic thinking) within a correlational design with 889 adult online distance students. In this study, we performed regression analyses and took age and processing speed into consideration, as processing speed and EFs decrease with age, whereas self-regulation is reported to increase with age. Cognitively measured working memory was not related to reported SRL-strategy use in adult ODE students. Thus, even though the SRL-components within the strategies seem to elicit working memory, reported SRL-strategy use is not related to the functioning of this basic EF (measured with cognitive tests). This means that if SRL-strategy use needs to be increased in adult ODE students, training of working memory might not be an effective manner for achieving that goal. Better shifting and processing speed were related to less reported SRL-strategy use, which might suggest that SRL-strategies might be used to compensate for lower shifting (in academic thinking) and lower processing speed (in simple cognitive strategy use and contacts with others). With increasing age, the number of contacts with peers or teachers decreases. This latter finding might be of relevance during the pandemic since contacts with others is importance during lockdown., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Meijs, Gijselaers, Xu, Kirschner and De Groot.)

Background: Information processing speed (IPS) is a marker for cognitive function. It is associated with neural maturation and increases during development. Traditionally, IPS is measured using paper and pencil tasks requiring fine motor skills. Such skills are often impaired in patients with neurological conditions. Therefore, an alternative that does not need motor dexterity is desirable. One option is the computerized symbol digit modalities test (c-SDMT), which requires the patient to verbally associate numbers with symbols., Methods: Eighty-six participants (8-16 years old; 45 male; 48 inpatients) were examined, 38 healthy and 48 hospitalized for a non-neurological disease. All participants performed the written SDMT, c-SDMT, and the Test of Non-verbal Intelligence Fourth Edition (TONI-4). Statistical analyses included a multivariate analysis of covariance (MANCOVA) for the effects of intelligence (IQ) and hospitalization on the performance of the SDMT and c-SDMT. A repeated measures analysis of variance (repeated measures ANOVA) was used to compare performance across c-SDMT trials between inpatients and outpatients., Results: The MANCOVA showed that hospitalization had a significant effect on IPS when measured with the SDMT ( p = 0.04) but not with the c-SDMT ( p = 0.68), while IQ ( p = 0.92) had no effect on IPS. Age ( p < 0.001) was the best predictor of performance of both tests. The repeated measures ANOVA revealed no significant difference in within-test performance ( p = 0.06) between outpatient and inpatient participants in the c-SDMT., Conclusion: Performance of the c-SDMT is not confounded by hospitalization and gives within-test information. As a valid and reliable measure of IPS for children and adolescents, it is suitable for use in both inpatient and outpatient populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Klein, Jufer-Riedi, Rieder, Hochstrasser, Steiner, Cao, Feinstein, Bigi and Lidzba.)

Purpose: Exercise training reveals high potential to beneficially impact cognitive performance in persons with multiple sclerosis (pwMS). Research indicates that high-intensity interval training (HIIT) has potentially higher effects on physical fitness and cognition compared to moderate continuous exercise. This study (i) compares the effects of a 3-week HIIT and moderate continuous exercise training on cognitive performance and cardiorespiratory fitness of pwMS in an overall analysis and (ii) investigates potential effects based on baseline cognitive status in a subgroup analysis. Methods: Seventy-five pwMS were randomly assigned to an intervention (HIIT: 5 × 1.5-min intervals at 95-100% HR max , 3 ×/week) or active control group (CG: 24 min continuous exercise at 65% HR max , 3 ×/week). Cognitive performance was assessed pre- and post-intervention with the Brief International Cognitive Assessment for MS (BICAMS). (I) To examine potential within (time) and interaction (time × group) effects in the overall analysis, separate analyses of covariance (ANCOVA) were conducted. (II) For the subgroup analysis, participants were divided into two groups [intact cognition or impaired cognition (>1.5 standard deviation (SD) compared to healthy, age-matched norm data in at least one of the three tests of the BICAMS]. Potential impacts of cognitive status and intervention were investigated with multivariate analyses of variance (MANOVA). Results: Overall analysis revealed significant time effects for processing speed, verbal learning, rel. VO2peak, and rel. power output. A time * group interaction effect was observed for rel. power output. Subgroup analysis indicated a significant main effect for cognition (impaired cognition vs. intact cognition). Subsequent post-hoc analysis showed significant larger effects on verbal learning in pwMS with impaired cognition. Conclusion: Current results need to be confirmed in a powered randomized controlled trial with cognitive performance as primary endpoint and eligibility based on cognitive performance that is assessed prior to study inclusion., Competing Interests: DL discloses research grants/consultancy/speaker bureau from Novartis, Merck, TEVA, Biogen, Sanofi, Bayer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rademacher, Joisten, Proschinger, Bloch, Gonzenbach, Kool, Langdon, Bansi and Zimmer.)

Background: Verbal fluency (VF) has been associated with several cognitive functions, but the cognitive processes underlying verbal fluency deficits in Multiple Sclerosis (MS) are controversial. Further knowledge about VF could be useful in clinical practice, because these tasks are brief, applicable, and reliable in MS patients. In this study, we aimed to evaluate the cognitive processes related to VF and to develop machine-learning algorithms to predict those patients with cognitive deficits using only VF-derived scores. Methods: Two hundred participants with MS were enrolled and examined using a comprehensive neuropsychological battery, including semantic and phonemic fluencies. Automatic linear modeling was used to identify the neuropsychological test predictors of VF scores. Furthermore, machine-learning algorithms (support vector machines, random forest) were developed to predict those patients with cognitive deficits using only VF-derived scores. Results: Neuropsychological tests associated with attention-executive functioning, memory, and language were the main predictors of the different fluency scores. However, the importance of memory was greater in semantic fluency and clustering scores, and executive functioning in phonemic fluency and switching. Machine learning algorithms predicted general cognitive impairment and executive dysfunction, with F1-scores over 67-71%. Conclusions: VF was influenced by many other cognitive processes, mainly including attention-executive functioning, episodic memory, and language. Semantic fluency and clustering were more explained by memory function, while phonemic fluency and switching were more related to executive functioning. Our study supports that the multiple cognitive components underlying VF tasks in MS could serve for screening purposes and the detection of executive dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Delgado-Álvarez, Matias-Guiu, Delgado-Alonso, Hernández-Lorenzo, Cortés-Martínez, Vidorreta, Montero-Escribano, Pytel and Matias-Guiu.)

Previous neuroimaging studies have identified structural brain abnormalities in active professional fighters with repetitive head trauma and correlated these changes with fighters' neuropsychological impairments. However, functional brain changes in these fighters derived using neuroimaging techniques remain unclear. In this study, both static and dynamic functional connectivity alterations were investigated (1) between healthy normal control subjects (NC) and fighters and (2) between non-impaired and impaired fighters. Resting-state fMRI data were collected on 35 NC and 133 active professional fighters, including 68 impaired fighters and 65 non-impaired fighters, from the Professional Fighters Brain Health Study at our center. Impaired fighters performed worse on processing speed (PSS) tasks with visual-attention and working-memory demands. The static functional connectivity (sFC) matrix was estimated for every pair of regions of interest (ROI) using a subject-specific parcellation. The dynamic functional connectivity (dFC) was estimated using a sliding-window method, where the variability of each ROI pair across all windows represented the temporal dynamics. A linear regression model was fitted for all 168 subjects, and different t-contrast vectors were used for between-group comparisons. An association analysis was further conducted to evaluate FC changes associated with PSS task performances without creating artificial impairment group-divisions in fighters. Following corrections for multiple comparisons using network-based statistics, our study identified significantly reduced long-range frontal-temporal, frontal-occipital, temporal-occipital, and parietal-occipital sFC strengths in fighters than in NCs, corroborating with previously observed structural damages in corresponding white matter tracts in subjects experiencing repetitive head trauma. In impaired fighters, significantly decreased sFC strengths were found among key regions involved in visual-attention, executive and cognitive process, as compared to non-impaired fighters. Association analysis further reveals similar sFC deficits to worse PSS task performances in all 133 fighters. With our choice of dFC indices, we were not able to observe any significant dFC changes beyond a trend-level increased temporal variability among similar regions with weaker sFC strengths in impaired fighters. Collectively, our functional brain findings supplement previously reported structural brain abnormalities in fighters and are important to comprehensively understand brain changes in fighters with repetitive head trauma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Zhuang, Mishra, Nandy, Yang, Sreenivasan, Bennett, Bernick and Cordes.)

Major depression (MDD) is associated with cognitive deficits in processing speed and executive function (EF) following first episode (FE). It is unclear whether deficits are state or trait related. Studies following FE MDD over longer periods are lacking, making it uncertain how cognition and symptoms develop after the initial episode. The present study assessed cognitive function and symptoms 5 years following FE MDD. In addition, the study explored relationships between MDD symptoms, rumination, and cognitive deficits with regards to the trait, state, and scar perspective. Twenty-three participants with previous FE MDD, and 20 matched control participants were compared on Delis-Kaplan Executive Function System measures of processing speed and EF, in a 5-year longitudinal follow-up study. Correlations between current symptoms- and history of MDD, rumination, cognition were investigated. Findings indicated that cognitive deficits persisted with no clear signs of exacerbation after initial episode. Inhibition appeared independent of current and previous symptoms of depression. Processing speed was related to depressive- symptoms and rumination. In conclusion, results indicated persisting, stable deficits in both EFs and processing speed. Findings further suggest that depressive symptoms could be related to deficits in processing speed, indicating state effects. There was limited support for worsening of cognition after initial episode. Some aspects of EF like Inhibition could show persistent deficits independent of depressive symptoms indicating trait effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Ronold, Schmid, Oedegaard and Hammar.)

To investigate the underlying mechanism of the relationship between visual working memory (VWM) and Chinese character recognition, and the moderation effect of processing efficiency on this relationship, 154 first-grade students were administered a battery of tasks for VWM, rapid temporal processing, and Chinese character reading. In the VWM task, the children were asked to remember the jumping routes of a frog and report these routes in reverse sequence. The longest span for which each participant could respond correctly at least four times out of six was the VWM index. In the task of temporal order judgement, the participants were asked to select which of two balls was presented first, with stimulus onset asynchronies varying from 8 to 492 ms according to an adaptive psychophysical procedure. Visual temporal order threshold (VTOT) was utilized as an indicator of processing efficiency. The participants were asked to read 100 characters aloud to measure their word-level reading abilities in Chinese character recognition. After controlling age, non-verbal intelligence, visual short-term memory, morphological awareness, and orthographic awareness, the results of a moderation effect analysis showed that (1) both VWM and visual VTOT predicted Chinese character reading, and (2) the moderation effect of VTOT on the VWM-reading link was significant ( p = 0.001). The correlation between VWM and Chinese character reading was positive and significant when VTOTs were above average (i.e., smaller than 87.14 ms); however, the correlation was negative at relatively poor levels of VTOTs (i.e., larger than 231.44 ms)., (Copyright © 2020 Xu, Wang, Liu, Chen and Tao.)

Words can either boost or hinder the processing of visual information, which can lead to facilitation or interference of the behavioral response. We investigated the stage (response execution or target processing) of verbal interference/facilitation in the response priming paradigm with a gender categorization task. Participants in our study were asked to judge whether the presented stimulus was a female or male face that was briefly preceded by a gender word either congruent (prime: "man," target: "man"), incongruent (prime: "woman," target: "man") or neutral (prime: "day," target: "man") with respect to the face stimulus. We investigated whether related word-picture pairs resulted in faster reaction times in comparison to the neutral word-picture pairs (facilitation) and whether unrelated word-picture pairs resulted in slower reaction times in comparison to neutral word-picture pairs (interference). We further examined whether these effects (if any) map onto response conflict or aspects of target processing. In addition, identity ("man," "woman") and associative ("tie," "dress") primes were introduced to investigate the cognitive mechanisms of semantic and Stroop-like effects in response priming (introduced respectively by associations and identity words). We analyzed responses and reaction times using the drift diffusion model to examine the effect of facilitation and/or interference as a function of the prime type. We found that regardless of prime type words introduce a facilitatory effect, which maps to the processes of visual attention and response execution., (Copyright © 2020 Todorova and Neville.)

Background: Although schizophrenia patients have been reported to manifest deficits in cognitive flexibility and lower processing speed (measured with i.a., the Color Trails Test, CTT), there still remain a few matters that require further investigation. We have therefore formulated three research aims: 1) to examine the factor structure of CTT in schizophrenia patients and healthy controls, 2) to compare different CTT performance measures in the two groups, 3) to investigate the relationship between these measures and selected psychopathological symptoms in the patient group., Methods: Sixty-seven patients with paranoid schizophrenia and 67 healthy controls, matched for gender, age, number of years of education, and overall cognitive functioning underwent assessment of cognitive flexibility and processing speed with the CTT., Results: Factor analysis of CTT variables based on the principal component method revealed a four-factor solution in both groups. Compared with healthy controls, the patients performed poorer on CTT 1 time, CTT 2 time, 2-1 difference, prompts in CTT 2, and had higher regression factor scores for Factor 1 (reflecting the slower speed of perceptual tracking). Furthermore, significant links were found between some CTT measures, and negative and disorganization symptoms., Conclusions: Schizophrenia patients exhibit problems with speed of perceptual tracking and executive processes dependent on processing speed. Our results may be useful for the development of neuropsychological diagnostic methods for schizophrenia patients. It seems that, compared to other CTT indices, CTT 1 time, CTT 2 time, and 2-1 difference are more appropriate measures of cognitive performance in schizophrenia patients., (Copyright © 2020 Tyburski, Karabanowicz, Mak, Lebiecka, Samochowiec, Pełka-Wysiecka, Sagan and Samochowiec.)

Age-related differences in white matter (WM) microstructure have been linked to lower performance in tasks of processing speed in healthy older individuals. However, only few studies have examined this link in a longitudinal setting. These investigations have been limited to the correlation of simultaneous changes in WM microstructure and processing speed. Still little is known about the nature of age-related changes in WM microstructure, i.e., regionally distinct vs. global changes. In the present study, we addressed these open questions by exploring whether previous changes in WM microstructure were related to subsequent changes in processing speed: (a) 1 year later; or (b) 2 years later. Furthermore, we investigated whether age-related changes in WM microstructure were regionally specific or global. We used data from four occasions (covering 4 years) of the Longitudinal Healthy Aging Brain (LHAB) database project ( N = 232; age range at baseline = 64-86). As a measure of WM microstructure, we used mean fractional anisotropy (FA) in 10 major WM tracts averaged across hemispheres. Processing speed was measured with four cognitive tasks. Statistical analyses were conducted with bivariate latent change score (LCS) models. We found, for the first time, evidence for lagged couplings between preceding changes in FA and subsequent changes in processing speed 2 years, but not 1 year later in some of the WM tracts (anterior thalamic radiation, superior longitudinal fasciculus). Our results supported the notion that FA changes were different between regional WM tracts rather than globally shared, with some tracts showing mean declines in FA, and others remaining relatively stable across 4 years., (Copyright © 2019 Oschwald, Mérillat, Liem, Röcke, Martin and Jäncke.)

Background: Major depressive disorder (MDD) is associated with a wide range of cognitive deficits. However, it remains unclear whether there will be a major cognitive deficit independently caused by depression at acute episodes of MDD. Method: A comprehensive neurocognitive test battery was used to assess the executive function, processing speed, attention, and memory in 162 MDD patients and 142 healthy controls (HCs). A multivariate analysis of variance, hierarchical regression analyses and general linear regression analyses were used to explore the possible major cognitive deficits and their predictor variables. Results: MDD patients showed extensive impairment in all four cognitive domains. Impairment of executive function and processing speed were found to persist even with other cognitive domains and clinical variables being accounted for. Executive function and processing speed were further predicted by total disease duration and depression severity, respectively. Conclusions: Executive function and processing speed may be two distinct major deficits at acute episodes of MDD. Furthermore, the executive function is likely originated from the cumulative effect of disease duration and processing speed is possibly derived from the temporary effect of current depressive episode., (Copyright © 2019 Liu, Dong, Lu, Sun, Zhang, Wang, Wan, Guo, Zhao, Ju, Yan, Li, Fang, Guo, Liao, Zhang, Zhang, Liu and Li.)

This study investigated the relationship between cognitive abilities and age differences in information search and the moderating role of task self-relevance by measuring the decision-making processes of participants in both high and low self-relevance decision-making tasks. The sample included 57 young and 65 older adults. They viewed five-alternative × five-attribute decision matrices that required them to open, with a mouse click, the information cells that interested them. Processing speed, verbal fluency, working memory, and vocabulary were measured as cognitive abilities. The dependent variables were search engagement (including time-related engagement and frequency-related engagement) and search pattern (calculated based on alternative-based or attribute-based search). The results from structured equation modeling showed that age negatively predicted these cognitive abilities (processing speed, verbal fluency, working memory, and vocabulary) and positively predicted information search engagement. Processing speed mediated the effect of age on study time per cell under tasks with both high and low self-relevance. Verbal fluency, meanwhile, mediated the total search time and checking time per cell when the task was highly self-related but not when the task had low self-relevance. These results suggest that self-relevance can moderate the mediation effect of verbal fluency on the relationship between age and information search time; this means that older adults whose verbal fluency was limited require relatively more time to search information to make an informed decision. However, this effect is only sufficient when the decision-making task is highly self-related and provokes more engagement motivation toward it.

It is suggested that the brain's peak width of skeletonized water mean diffusivity (PSMD) is a neuro-biomarker of processing speed, an important aspect of cognitive aging. We tested whether PSMD is more strongly correlated with processing speed than with other cognitive domains, and more strongly than other structural brain MRI indices. Participants were 731 Lothian Birth Cohort 1936 members, mean age = 73 years (SD = 0.7); analytical sample was 656-680. Cognitive domains tested were as follows: processing speed (5 tests), visuospatial (3), memory (3), and verbal (3). Brain-imaging variables included PSMD, white matter diffusion parameters, hyperintensity volumes, gray and white matter volumes, and perivascular spaces. PSMD was significantly associated with processing speed (-0.27), visuospatial ability (-0.23), memory ability (-0.17), and general cognitive ability (-0.25); comparable correlations were found with other brain-imaging measures. In a multivariable model with the other imaging variables, PSMD provided independent prediction of visuospatial ability and general cognitive ability. This incremental prediction, coupled with its ease to compute and possibly better tractability, might make PSMD a useful brain biomarker in studies of cognitive aging.

Background: Autonomic dysfunctions may precede the development of cognitive impairment, but the connection between these dimensions is unclear. This systematic review aims to analyze the relationship between heart rate variability (HRV) and cognitive functions. Methods: The review process was conducted according to the PRISMA-Statement. Restrictions were made, selecting the studies in English and published in peer-review journals, including at least one cognitive measure and presenting the measurement of HRV. Studies that included participants with medical conditions, dementia, psychiatric disorders, strokes, and traumatic brain injury were excluded. Twenty studies were selected, with a total of 19,431 participants. The results were divided into different cognitive domains determined a priori : global cognitive functioning, attention, processing speed, executive functions, memory, language and visuospatial skills. Results: Both increased sympathetic activity and decreased parasympathetic activity seem to be associated with a worse performance in the cognitive domains considered, in the absence of dementia and severe cardiovascular diseases or other medical and psychiatric diseases. Conclusion: The results highlight the influence of the autonomic nervous system (ANS) in cognitive functioning. However, the marked interest facing toward a specific domain, i.e., the executive functions, and the relatively small number of the studies on this topic do not allow understanding better this relationship. Despite these limits, HRV could be considered a promising early biomarker of cognitive impairment in populations without dementia or stroke. This index should be evaluated within a preventative perspective to minimize the risk of developing cognitive impairment.

Objective: Cognition and mobility are interrelated. However, this association can be impacted by the specific facets of cognition and mobility that are measured, and further by the different task conditions, e.g., single- versus dual-task walking, under which these associations are evaluated. Systematically studying the multiple facets of cognitive-mobility associations under both the task conditions is critical because both cognition and mobility change with age and pose significant risks associated with falls, morbidity, and disability., Methods: Using a cross-sectional, prospective study design, data from 124 healthy adults [mean age (SD) = 61.51 (11.90); mean education (SD) = 15.94 (2.18)] were collected. A comprehensive battery of cognitive tests was administered, and gait was assessed using a small, lightweight, three-axis accelerometer with a gyroscope., Analytical Plan: Data were transformed, and only relatively strong relationships survived after strict statistical criteria adjusting for multiple comparisons were applied. Spearman rho correlation coefficients were used to examine the matrix of correlations between the cognitive-motor variables while adjusting for age and gender., Results: Executive functions, processing speed, and language were associated with distinct facets of variability, pace, and asymmetry, especially under the dual-task walking condition. Both turns and transitions were also associated with cognition during the Timed Up and Go Task., Conclusion: Our results extend converging evidence of the involvement of executive functions and processing speed in specific aspects of mobility, along with the role of language. The study has important implications for aging in terms of both assessment and rehabilitation of cognition and gait as well as for the emerging dual-tasking theories and the role of the neural pathways involved in mobility.

Cognitive impairment has been reported at all phases and all subtypes of multiple sclerosis. It remains a major cause of neurological disability in young and middle-aged adults suffering from the disease. The severity and type of cognitive impairment varies considerably among individuals and can be observed both in early and in later stages. The areas which have commonly shown more deficits are: information processing speed, complex attention, memory, and executive function. Even though an alteration in both the white matter and in the gray matter has been found in patients with multiple sclerosis and cognitive impairment, the underlying process still remains unknown. Standardized neurological examinations fail to detect emerging cognitive deficits and self-reported cognitive complaints by the patients can be confounded by other subjective symptoms. This review is a comprehensive and short update of the literature on cognitive dysfunctions, the possible confounders and the impact of quality of life in patients with multiple sclerosis.

Decline in information processing with age is well-documented in the scientific literature. However, some discrepancy remains in relation to which cognitive domains are most susceptible to the aging process and which may remain intact. Furthermore, information processing has not been investigated nor considered as a function of affect, familiarity and complexity of tasks in a single experimental study. Thus, the current study investigated rate of visual information processing in 67 young university students ( M age = 19.64 years) and 33 educated healthy older adults ( M age = 70.33 years), while accounting for depression, anxiety and stress symptoms using the DASS. Rates of visual processing were measured as minimum time of stimulus exposure duration required for correct object recognition on a simple visual task [Inspection Time (IT)], and on a more complex visual cognitive task known as Change Detection (CD)] as well as words per minute on a text reading task (FastaReada). The results demonstrated significantly slower performance by older adults on the IT and CD, but comparable rates of text reading on a semantically more complex, but ecologically valid and familiar visual task that requires organized sequential shifts in attention via eye movements, continuous visual processing, access to working memory and semantic comprehension. The results also demonstrated that affective influences did not play a role in the older adults task performance, and that changes in cognitive domains may begin with older adults being slower to attend to and identify newly appearing familiar objects, as well as slower to encode and embed new information in memory during tasks that require a less practiced/familiar task strategy.