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Background and ObjectiveWhile underlying pathophysiology linking obesity to brain health is not completely understood, white adipose tissue (WAT) is considered a key player. In obesity, WAT becomes dysregulated, showing hyperplasia, hypertrophy, and eventually inflammation. This disbalance leads to dysregulated secretion of adipokines influencing both (cardio)vascular and brain health. Within this study, we investigated the association between omental WAT (oWAT) and subcutaneous WAT (scWAT) with brain structure and perfusion and cognition in adults with severe obesity.MethodsWithin the cross-sectional BARICO study, brain structure and perfusion and cognitive function were measured before bariatric surgery (BS) using MRI and cognitive assessments. During BS, oWAT and scWAT depots were collected and analyzed by histopathology. The number and diameter of adipocytes were quantified together with the amount of crown-like structures (CLS) as an indication of inflammation. Blood samples were collected to analyze adipokines and inflammatory markers. Neuroimaging outcomes included brain volumes, cortical thickness, white matter (WM) integrity, WM hyperintensities, cerebral blood flow using arterial spin labeling (ASL), and the ASL spatial coefficient of variation (sCoV), reflecting cerebrovascular health.ResultsSeventy-one patients were included (mean age 45.1 ± 5.8 years; 83.1% women; mean body mass index 40.8 ± 3.8 kg/m2). scWAT showed more CLS (z= −2.72,p< 0.01,r= −0.24) and hypertrophy compared with oWAT (F(1,64) = 3.99,p< 0.05, η2= 0.06). Adiponectin levels were inversely associated with the average diameter of scWAT (β = −0.31, 95% CI −0.54 to −0.08) and oWAT (β = −0.33, 95% CI −0.55 to −0.09). Furthermore, the adipocyte diameter in oWAT was positively associated with the sCoV in the parietal cortex (β = 0.33, 95% CI 0.10–0.60), and the number of adipocytes (per mm2) was positively associated with sCoV in the nucleus accumbens (NAcc) (β = 0.34, 95% CI 0.09–0.61). Cognitive function did not correlate with any WAT parameter or plasma marker. These associations were highly influenced by age and sex. sCoV in the NAcc was positively associated with fasting plasma glucose (β = 0.35, 95% CI 0.10–0.56).DiscussionscWAT and oWAT are different in morphology and in their relationship with plasma markers and cerebrovascular health. Although scWAT showed more CLS and hypertrophy, scWAT was not associated with brain readouts. This study showed, however, important relationships between oWAT morphology and cerebrovascular health in obesity.Trial Registration InformationTrial Registration Number NTR7288 (trialregister.nl/trial/7090).

Contains fulltext : 290087.pdf (Publisher’s version ) (Open Access) Background: Cognitive problems, both complaints and objective impairments, are frequent and disabling in patients with multiple sclerosis (MS) and profoundly affect daily living. However, intervention studies that focus on cognitive problems that patients experience in their daily lives are limited. This study therefore aimed to investigate the effectiveness of cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT) on patient-reported cognitive complaints in MS. Methods: In this randomized-controlled trial, MS patients with cognitive complaints completed questionnaires and underwent neuropsychological assessments at baseline, post-treatment and 6-month follow-up. Patient-reported cognitive complaints were primarily investigated. Secondary outcomes included personalized cognitive goals and objective cognitive function. CRT and MBCT were compared to enhanced treatment as usual (ETAU) using linear mixed models. Results: Patients were randomized into CRT (n = 37), MBCT (n = 36) or ETAU (n = 37), of whom 100 completed the study. Both CRT and MBCT positively affected patient-reported cognitive complaints compared to ETAU at post-treatment (p

Background: Structural network damage is a potentially important mechanism by which cerebral small vessel disease (SVD) can cause cognitive impairment. As a central hub of the structural network, the role of thalamus in SVD-related cognitive impairments remains unclear. We aimed to determine the associations between the structural alterations of thalamic subregions and cognitive impairments in SVD. Methods: In this cross-sectional study, 205 SVD participants without thalamic lacunes from the third follow-up (2020) of the prospective RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort), which was initiated in 2006, Nijmegen, were included. Cognitive functions included processing speed, executive function, and memory. Probabilistic tractography was performed from thalamus to 6 cortical regions, followed by connectivity-based thalamic segmentation to assess each thalamic subregion volume and connectivity (measured by mean diffusivity [MD] of the connecting white matter tracts) with the cortex. Least absolute shrinkage and selection operator regression analysis was conducted to identify the volumes or connectivity of the total thalamus and 6 thalamic subregions that have the strongest association with cognitive performance. Linear regression and mediation analyses were performed to test the association of least absolute shrinkage and selection operator-selected thalamic subregion volume or MD with cognitive performance, while adjusting for age and education. Results: We found that higher MD of the thalamic-motor tract was associated with worse processing speed (β=−0.27; P P =0.001), and memory (β=−0.28; P Conclusions: Our results suggest that the structural alterations of thalamus are linked to cognitive impairment in SVD, largely depending on the damage pattern of the white matter tracts connecting specific thalamic subregions and cortical regions.

Objective:While declarative learning is dependent on the hippocampus, procedural learning and repetition priming can operate independently from the hippocampus, making them potential targets for behavioral interventions that utilize non-declarative memory systems to compensate for the declarative learning deficits associated with hippocampal insult. Few studies have assessed procedural learning and repetition priming in individuals with amnestic mild cognitive impairment (aMCI).Method:This study offers an overview across declarative, conceptual repetition priming, and procedural learning tasks by providing between-group effect sizes and Bayes Factors (BFs) comparing individuals with aMCI and controls. Seventy-six individuals with aMCI and 83 cognitively unimpaired controls were assessed. We hypothesized to see the largest differences between individuals with aMCI and controls on declarative learning, followed by conceptual repetition priming, with the smallest differences on procedural learning.Results:Consistent with our hypotheses, we found large differences between groups with supporting BFs on declarative learning. For conceptual repetition priming, we found a small-to-moderate between-group effect size and a non-conclusive BF somewhat in favor of a difference between groups. We found more variable but overall trivial differences on procedural learning tasks, with inconclusive BFs, in line with expectations.Conclusions:The current results suggest that conceptual repetition priming does not remain intact in individuals with aMCI while procedural learning may remain intact. While additional studies are needed, our results contribute to the evidence-base that suggests that procedural learning may remain spared in aMCI and helps inform behavioral interventions that aim to utilize procedural learning in this population.

OBJECTIVE Hypoglycemia poses an immediate threat for cognitive function. Due to its association with acute cognitive impairment, the International Hypoglycemia Study Group (IHSG) defines a blood glucose level RESEARCH DESIGN AND METHODS Adults with type 1 diabetes with normal (n = 26) or impaired (n = 21) hypoglycemic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglycemic-hypoglycemic glucose clamp (2.80 ± 0.13 mmol/L [50.2 ± 2.3 mg/dL]). At baseline and during hypoglycemia, calculation ability, attention, working memory and cognitive flexibility were measured with the Paced Auditory Serial Addition Test (PASAT) and the Test of Attentional Performance (TAP). RESULTS For the whole group, hypoglycemia decreased the mean ± SD proportion of correct answers on the PASAT by 8.4 ± 12.8%, increased reaction time on the TAP Alertness task by 32.1 ± 66.6 ms, and increased the sum of errors and omissions on the TAP Working Memory task by 2.0 ± 5.5 (all P < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA1c. CONCLUSIONS IHSG level 2 hypoglycemia impairs cognitive function in people with and without diabetes, irrespective of type of diabetes or hypoglycemia awareness status. These findings support the cutoff value of hypoglycemia

Contains fulltext : 234323.pdf (Publisher’s version ) (Open Access) Feedback of neuropsychological test results to patients and family members include psychoeducation and implications for daily life. This scoping review aimed to provide an overview of the literature on neuropsychological feedback and to offer clinical recommendations. In accordance with formal scoping review methodology, PubMed, PsycInfo, Web of Science, CINAHL, and Embase databases were searched. Studies were included if they reported on neuropsychological feedback, if full papers were available, and if they included human participants. All languages were included, and no limit was placed on the year of publication. Of the 2,173 records screened, 34 publications met the inclusion criteria. Five additional publications were included after cross-referencing. An update of the search led to the inclusion of two additional papers. Of these 41 publications, 26 were research papers. Neuropsychological feedback is provided for a wide spectrum of diagnoses and usually given in-person and has been related to optimal a positive effect on patient outcomes (e.g. increase the quality of life). Most papers reported on satisfaction and found that satisfaction with an NPA increased when useful feedback was provided. However, information retention was found to be low, but communication aids, such as written information, were found to be helpful in improving retention. The current review demonstrated the benefits of neuropsychological feedback and that this should be part of standard clinical procedures when conducting a neuropsychological assessment. Further research on the benefits of neuropsychological feedback and how to improve information provision would enrich the neuropsychological literature. 22 p.

IntroductionMany individuals with acquired brain injury tend to experience problems with slowed information processing speed (IPS). A potentially beneficial and cost-effective supplement for cognitive rehabilitation of impaired IPS may be the implementation of serious gaming that focus on compensatory learning as part of cognitive training. However, most digital platforms that are used during cognitive rehabilitation have been focused on restoration of cognitive function, and limited evidence has been found for the generalization of skills that are trained during cognitive rehabilitation to everyday life.ObjectiveThe aim of this study is to investigate the efficacy of a game-supported cognitive strategy training. The training combines a well-validated time pressure management (TPM) cognitive strategy training targeting slowed IPS with a novel game and a mobile application. The game-supported training focuses on the generalization of strategy-use to untrained tasks in everyday life.Methods and analysisThe study is designed as a randomized controlled trial in which the experimental group (Karman Line Tempo module: an 8-week game-supported cognitive strategy training) will be compared with an active control group (CogniPlus™ training: an 8-week computerized cognitive function training). Data from 60 individuals with acquired brain injury (30 per group, ages between 18 and 70) will be collected at baseline (T0), post-treatment (T1) and at 3-month follow-up (T2). Primary outcome measure is an objective assessment of compensatory strategy-use in an untrained experimental task. Secondary outcome is the attainment of trained and untrained treatment goals assessed by goal attainment scaling (GAS). Pre- and post-training data will be analysed using a 2×2 repeated measure analysis of variance.Ethics and disseminationThis study has been approved by the medical review ethics committee CMO Region Arnhem and Nijmegen (NL74818.091.20) and is registered in the Netherlands Trial Register (NL9437). Research findings will be published in peer-reviewed journals and at conferences.Strengths & Limitations-This study is the first to investigate a compensatory approach in serious gaming, combined with a scientifically validated cognitive training, as an intervention for slowed information processing speed in acquired brain injury.-An adequately powered randomized controlled trial design with block randomization and an active control group to control for confounding effects of computer training in a rehabilitation setting.-Outcome variables that measure the generalization of the intervention to everyday life, especially to the level of activities and participation, in addition to improvement on neuropsychological tests.-To balance sufficient power and the feasibility of the study, a sample size of sixty individuals with ABI will be included in the study.-No 3-month follow-up of the primary outcome measure is included, as only two parallel versions of the Virtual Meeting Task are available.

OBJECTIVE Hypoglycemia poses an immediate threat for cognitive function. Due to its association with acute cognitive impairment, the International Hypoglycemia Study Group (IHSG) defines a blood glucose level RESEARCH DESIGN AND METHODS Adults with type 1 diabetes with normal (n=26) or impaired (n=21) hypoglycemic awareness, or with insulin-treated type 2 diabetes (n=15) and age-matched controls without diabetes (n=32) underwent a hyperinsulinemic-euglycemic hypoglycemic glucose clamp (2.80 ± 0.13 mmol/L [50.2 ± 2.3 mg/dL]). At baseline and during hypoglycemia, calculation ability, attention, working memory and cognitive flexibility were measured with the Paced Auditory Serial Addition Test (PASAT) and the Test of Attentional Performance (TAP). RESULTS For the whole group, hypoglycemia decreased the proportion of correct answers on the PASAT by 8.4 ± 12.8%, increased the mean reaction time on the TAP Alertness task by 32.1 ± 66.6 ms, and increased the sum of errors and omissions on the TAP Working Memory task by 2.0 ± 5.5 (all p < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration or HbA1c. CONCLUSIONS IHSG level 2 hypoglycemia impairs cognitive function in people with and without diabetes, irrespective of type of diabetes or hypoglycemia awareness status. These findings support the cut-off value of hypoglycemia

Background and Objectives:Compensation strategies are essential in Parkinson’s disease (PD) gait rehabilitation. However, besides external cueing, these strategies have rarely been investigated systematically. We aimed to: (1) establish the patients’ perspective on the efficacy and usability of five different compensation strategies; (2) quantify the efficacy of these strategies on spatiotemporal gait parameters; and (3) explore associations between the effects of specific strategies and patient characteristics.Methods:We recruited persons with PD and self-reported disabling gait impairments for this lab-based, within-subject study. Clinimetrics included: questionnaires (NFOG-Q, VMIQ-2, GMSI), cognitive assessments (ANT, MoCA, Brixton), and physical examinations (MDS-UPDRS III, Mini-BEST, tandem gait, rapid turns test). Gait assessment consisted of six 3-minute trials of continuous walking around a 6-meter walkway. Trials comprised: 1) baseline gait; 2) external cueing; 3) internal cueing; 4) action observation; 5) motor imagery; and 6) adopting a new walking pattern. Spatiotemporal gait parameters were acquired using 3D motion capture analysis. Strategy efficacy was determined by the change in gait variability compared to baseline gait. Associated patient characteristics were explored using regression analyses.Results:101 participants (50 men; median[range] age: 66[47-91] years) were included. The effects of the different strategies varied greatly among participants. While participants with higher baseline variability showed larger improvements using compensation strategies, participants without freezing of gait, with lower MDS-UPDRS III scores, higher balance capacity and better performance in orienting attention, also showed greater improvements in gait variability. Higher MoCA scores were associated with greater efficacy of external cueing.Discussion:Our findings support the use of compensation strategies in gait rehabilitation for PD, but highlight the importance of a personalized approach. Even patients with high gait variability are able to improve through the application of compensation strategies, but certain levels of cognitive and functional reserve seem necessary to optimally benefit from them.Classification of Evidence:This study provides Class III evidence that gait compensation strategies can be effective in persons with PD.

Item does not contain fulltext In this commentary, we highlight the role of the hippocampus as a binding device that may explain its recruitment during associative working-memory paradigms. Furthermore, we argue that both functional neuroimaging research, as presented in Slotnick (this issue), and carefully designed lesion studies in patients with selective bilateral hippocampal damage are crucial for advancing our understanding of the neural structures and processing involved in human memory in general and disentangling the role of the hippocampus proper and other medial temporal lobe structures in working-memory function and long-term encoding specifically. 2 p.

Background: Benzodiazepines are widely used in the treatment of anxiety disorders and sleep disturbances, but negative cognitive side effects have been reported after long-term use. Studies on the cognitive effects of long-term benzodiazepine use to date have typically included small samples and limited cognitive assessments. Objectives: This study examined cognitive performance on four cognitive domains in long-term benzodiazepine users, compared to normative data. Furthermore, it was examined whether sex, age, benzodiazepine dose, and state and trait anxiety moderated cognitive functioning in long-term benzodiazepine users. Methods: Neuropsychological tests targeting different cognitive domains were administered to 92 patients with long-term benzodiazepine use who were accepted for enrolment into a benzodiazepine discontinuation programme in an academic hospital. Test scores were compared to a large normative data sample. Results: Of the long-term benzodiazepine users, 20.7% could be classified as cognitively impaired across all domains, with the largest effects found in the domains processing speed and sustained attention, and an overall worse performance in women, an effect which appears to be moderated by state anxiety. No effects of age or benzodiazepine dose were found. Conclusions: These results extend those of earlier studies on benzodiazepine effects on specific cognitive domains. This study implies an overall detrimental cognitive effect in long-term benzodiazepine users rather than specific effects. Therefore, long-term benzodiazepine use should be avoided, and once present, tailored interventions aimed at tapering benzodiazepines are warranted.

Background: Recent evidence indicates that disrupted sleep could contribute to the development of Alzheimer’s disease by influencing the production and/or clearance of the amyloid-β protein. We set up a case-control study to investigated the association between long-term work-induced sleep disruption, cognitive function, and brain amyloid-β accumulation.Methods: We recruited 19 male maritime pilots (aged 48-60 years) with chronic work-related sleep disruption and a sex-, age and education-matched control sample (n=16, aged 50-60 years) with normal sleep. Primary sleep disorders were ruled out with in-lab polysomnography. Additional sleep measurements were obtained at home using actigraphy, sleep-wake logs, and a single-lead EEG device. Cognitive function was assessed with a neuropsychological test battery sensitive to early symptomatic Alzheimer’s disease. Brain amyloid-β accumulation was assessed in maritime pilots using 18 F-flutemetamol amyloid PET-CT.Results: Maritime pilots reported significantly worse sleep quality (Pittsburgh Sleep Quality Index (PSQI)=8.8±2.9) during workweeks, compared to controls (PSQI=3.2±1.4; 95% CI 0.01 to 2.57; p =0.049). This was confirmed with actigraphy-based sleep efficiency (86% ±3.8 vs. 89.3% ±4.3; 95% CI 0.43 to 6.03; p =0.03). Home-EEG recordings showed less total sleep time and deep sleep time during workweeks compared to rest-weeks (TST: 318.56 (250.21–352.93) vs. TST: 406.17 (340–425.98); p =0.001; DST: 36.75 (32.30–58.58) vs. DST 51.34 (48.37–69.30); p =0.005)). There were no differences in any of the cognitive domains between the groups. Abnormal amyloid-β accumulation was ruled out, showing mean global cortical standard uptake value ratios in the normal range (1.009 ±0.059; 95% CI 0.980 to 1.037), confirmed by visual reads.Conclusions: Capitalizing on the particular work-rest schedule of maritime pilots, we show that long-term intermittent sleep disruption is not associated with brain amyloid accumulation or cognitive decline.

Background: Patients with mild cognitive impairment (MCI) have to deal with an uncertain prognosis and also face a multitude of memory-related problems and psychosocial consequences. A newly developed group programme proved to be feasible, however, it needed confirmation by a controlled study. Aim: This controlled study evaluates this group therapy for MCI patients aimed to help them accept and manage the memory problems and the psychosocial consequences. The programme combines elements from psychoeducation, cognitive rehabilitation and cognitive-behavioural therapy. Patients and Methods: Ninety-three MCI patients received treatment, with 30 patients being first assigned to a waiting list, thus serving as their own control group. Pre- and post-treatment acceptance and helplessness were assessed using subscales of the Illness Cognition Questionnaire, while distress and general well-being were gauged with the Geriatric Depression Scale and subscales of the RAND-36. Results: Linear mixed model analyses showed that, relative to the controls, acceptance had increased more in the intervention group compared to the waiting-list period (p = 0.034). Distress and general well-being showed no changes. Treatment responders demonstrating a clinically significant effect on acceptance and two of three secondary outcome measures had higher baseline levels of helplessness and fewer self-reported memory complaints in daily life than patients who did not improve. Conclusion: The intervention helped the patients deal better with their uncertain future in that they were overall better able to accept their condition, with especially the female patients showing a decrease in helplessness cognitions, although the effects were relatively small.

Objective: To evaluate the feasibility and present preliminary results of a cognitive behavioural group therapy for patients with mild cognitive impairment and their significant others. Design: One group pretest—posttest design. Subjects: Twenty-two patients with mild cognitive impairment and their significant others, running in four group programmes. Intervention: The main goal of the cognitive behavioural group therapy was to strengthen adaptive behaviour in 10 weekly 2-hour sessions. Main measures: Distress and mood: The RAND-36, Geriatric Depression Scale — short form; Acceptance and helplessness: Subscales Acceptance and Helplessness from the Illness Cognition Questionnaire; Marital satisfaction: Maudsley Marital Questionnaire; Alertness to memory failure and behaviour changes: Informant Questionnaire on Cognitive Decline in the Elderly and the Revised Memory and Behaviour Problems Checklist Burden. The burden of caregiving reported by the significant others: Sense of competence Questionnaire and Behaviour Problems Checklist Burden, Hindrance subscale. Results: No changes were found on distress and mood measures in both patients and their significant others. Patients showed a significant increased level of acceptance (P Conclusion: Preliminary results show evidence for positive changes after a cognitive behavioural group therapy for patients with mild cognitive impairment and their significant others. In addition, the developed programme is applicable and feasible. The programme's effectiveness should be studied further, with an estimated sample size of 70 couples in a controlled study design.

Serge JW Walvoort,1–3 Paul T van der Heijden,3,4 Roy PC Kessels,1,2,5 Jos IM Egger1–3,6 1Centre of Excellence for Korsakoff and Alcohol-Related Cognitive Disorders, Vincent van Gogh Institute for Psychiatry, Venray, 2Donders Institute for Brain, Cognition and Behaviour, 3Behavioural Science Institute, Radboud University, Nijmegen, 4Reinier van Arkel Mental Health Institute, ‘s-Hertogenbosch, 5Department of Medical Psychology, Radboud University Medical Center, Nijmegen, 6Centre of Excellence for Neuropsychiatry, Vincent van Gogh Institute for Psychiatry, Venray, the Netherlands Aim: Impaired illness insight may hamper treatment outcome in patients with alcohol-related cognitive deficits. In this study, a short questionnaire for the assessment of illness insight (eg, the Q8) was investigated in patients with Korsakoff’s syndrome (KS) and in alcohol use disorder (AUD) patients with mild neurocognitive deficits. Methods: First, reliability coefficients were computed and internal structure was investigated. Then, comparisons were made between patients with KS and patients with AUD. Furthermore, correlations with the Dysexecutive Questionnaire (DEX) were investigated. Finally, Q8 total scores were correlated with neuropsychological tests for processing speed, memory, and executive function. Results: Internal consistency of the Q8 was acceptable (ie, Cronbach’s α =0.73). The Q8 items represent one factor, and scores differ significantly between AUD and KS patients. TheQ8 total score, related to the DEX discrepancy score and scores on neuropsychological tests as was hypothesized, indicates that a higher degree of illness insight is associated with a higher level of cognitive functioning. Conclusion: The Q8 is a short, valid, and easy-to-administer questionnaire to reliably assess illness insight in patients with moderate-to-severe alcohol-related cognitive dysfunction. Keywords: illness insight, anosognosia, alcohol use disorder, Korsakoff’s syndrome, cognition, neuropsychological assessment

Contains fulltext : 118735.pdf (Publisher’s version ) (Closed access) The present study examines the long-term effects of a 10-session cognitive behavioural group therapy for patients with mild cognitive impairment (MCI) and their significant others 6 to 8 months after completion of the intervention. Forty-seven MCI patients and 47 significant others participated in the follow-up assessment. Results of the RAND-36, Illness Cognition Questionnaire, IQCODE, GDS-15 and Sense of Competence Questionnaire at follow-up were compared with the post-intervention assessment. Our findings showed that the increased level of acceptance in the MCI patients was maintained at follow-up, with an increased insight into their cognitive decline compared with post-intervention assessment (p < 0.001). In both the patients and the significant others, helplessness and wellbeing were worse at follow up (p < 0.05), but sense of competence increased in the significant others (p