Cognitive impairment in chronic obstructive pulmonary disease:disease burden, determinants and possible future interventions

Introduction: Cognitive impairment (CI) is an important but an under-recognized extra-pulmonary feature of chronic obstructive pulmonary disease (COPD). It is related to the burden of disability, worse health outcomes, and impaired self-management. Areas covered: CI includes deterioration of a wide range of cognitive functions, such as memory and various executive functions. Risk of hospitalization might be higher in patients with COPD compared to those without, with CI negatively impacting the wellbeing of patients with COPD. Disease-specific factors such as hypoxemia and inflammation, lifestyle factors such as dietary insufficiencies and lack of physical activity, and comorbidities such as obstructive sleep apnea and depression are likely to synergistically contribute to the development of CI in COPD. Tailored interventions can possibly improve CI in COPD, but this needs further investigation. Expert commentary: Further research is warranted involving the optimization of neuropsychological testing for screening and outcome assessment, longitudinal studies to investigate the development of CI in COPD over time, and randomized clinical trials to test the feasibility and efficacy of promising interventions.</p

SK2 channels in cerebellar Purkinje cells contribute to excitability modulation in motor-learning-specific memory traces

Neurons store information by changing synaptic input weights. In addition, they can adjust their membrane excitability to alter spike output. Here, we demonstrate a role of such "intrinsic plasticity" in behavioral learning in a mouse model that allows us to detect specific consequences of absent excitability modulation. Mice with a Purkinje-cell-specific knockout (KO) of the calcium-activated K+ channel SK2 (L7-SK2) show intact vestibulo-ocular reflex (VOR) gain adaptation but impaired eyeblink conditioning (EBC), which relies on the ability to establish associations between stimuli, with the eyelid closure itself depending on a transient suppression of spike firing. In these mice, the intrinsic plasticity of Purkinje cells is prevented without affecting long-term depression or potentiation at their parallel fiber (PF) input. In contrast to the typical spike pattern of EBC-supporting zebrin-negative Purkinje cells, L7-SK2 neurons show reduced background spiking but enhanced excitability. Thus, SK2 plasticity and excitability modulation are essential for specific forms of motor learning

Fatigue in patients with chronic disease:results from the population-based Lifelines Cohort Study

(1) To evaluate the prevalence of severe and chronic fatigue in subjects with and without chronic disease; (2) to assess to which extent multi-morbidity contributes to severe and chronic fatigue; and (3) to identify predisposing and associated factors for severe and chronic fatigue and whether these are disease-specific, trans-diagnostic, or generic. The Dutch Lifelines cohort was used, including 78,363 subjects with (n = 31,039, 53 ± 12 years, 33% male) and without (n = 47,324, 48 ± 12 years, 46% male) ≥ 1 of 23 chronic diseases. Fatigue was assessed with the Checklist Individual Strength-Fatigue. Compared to participants without a chronic disease, a higher proportion of participants with ≥ 1 chronic disease were severely (23% versus 15%, p < 0.001) and chronically (17% versus 10%, p < 0.001) fatigued. The odds of having severe fatigue (OR [95% CI]) increased from 1.6 [1.5–1.7] with one chronic disease to 5.5 [4.5–6.7] with four chronic diseases; for chronic fatigue from 1.5 [1.5–1.6] to 4.9 [3.9–6.1]. Multiple trans-diagnostic predisposing and associated factors of fatigue were found, explaining 26% of variance in fatigue in chronic disease. Severe and chronic fatigue are highly prevalent in chronic diseases. Multi-morbidity increases the odds of having severe and chronic fatigue. Several trans-diagnostic factors were associated with fatigue, providing a rationale for a trans-diagnostic approach

The relation between reinforcement sensitivity and self-reported, simulated and on-road driving in older drivers

Previous studies on older drivers show that diminishing functional (i.e. visual, motor and cognitive) abilities influence driving behavior. Research on young novice drivers, has shown that personality factors such as reinforcement sensitivity play a role in driving behavior. This relation however, has been understudied in older drivers. The present study investigated the relationship between reinforcement sensitivity and driving in older drivers at risk of diminished driving ability. Driving was assessed by self-report measures (i.e., Driver Behavior Questionnaire), a simulated driving task and an on-road driving assessment. Both general driving as well as specific aspects of driving (i.e. speed, standard deviation of lateral position I SDP], reactions to unexpected events) were considered. Reinforcement sensitivity was assessed by means of the classical BIS\BAS self-report instrument. Additionally, as this has been shown already for adolescents, it was investigated whether behavioral inhibition can function as a surrogate measure of reinforcement sensitivity, by studying the relation between behavioral inhibition and reinforcement sensitivity in the current sample of older adults. Reinforcement sensitivity predicted self-report driving but simulated and on-road driving were mainly predicted by age. In specific aspects of simulated driving, reinforcement sensitivity played only a minor role. The fact that reinforcement sensitivity was related to self-reported driving provides support for the hypothesis that personality differences have a direct influence on older drivers' self-assessment and possibly on self-regulation and ceasing to drive decisions. Behavioral inhibition was unrelated to reinforcement sensitivity in older drivers and can therefore not function as a surrogate measure of reinforcement sensitivity. (C) 2018 Elsevier Ltd. All rights reserved

Physical and mental fatigue in people with non-communicable chronic diseases

BACKGROUND: Fatigue is frequently reported in people with a non-communicable chronic disease. More insight in the nature of this symptom may enhance targeted treatment of fatigue. In this study, we aimed to gain more insight in the prevalence of different types of fatigue and in current prescribed treatment strategies to reduce fatigue in non-communicable chronic diseases. METHODS: People with non-communicable chronic diseases were contacted via public, non-profit, disease-specific health funds and patient associations and invited to complete a web-based survey. The survey included a general question about the experience ("Do you now or have you ever had complaints of fatigue?") and nature of fatigue (physically/mentally/combination), the Checklist Individual Strength-subscale subjective fatigue (CIS-Fatigue; 8-56 points), self-constructed questions for the distinction between physical and mental fatigue (both 3-21 points) and questions on prescribed treatments for fatigue. RESULTS: In total, 4199 participants (77% females) completed the online survey. 3945 participants (94.0%) reported experiencing fatigue, of which 64.4% reported a combination of both physical and mental fatigue. Median CIS-Fatigue score was 41 (32-48) points, with 68% of the participants reporting severe fatigue (≥36 points). Median scores for physical and mental fatigue were 15 (11-18) and 12 (8-16) points, respectively. In 55% of the participants, fatigue was only occasionally or never discussed with the healthcare professional, and only 23% of the participants were prescribed a treatment for fatigue. Participants often reported no effect or even an increase in fatigue after treatment. CONCLUSIONS: Findings indicate that both physical and mental fatigue are often experienced simultaneously in people with non-communicable chronic diseases, but can also occur separately. Fatigue is often only occasionally or never discussed, let alone treated, highlighting the need to raise awareness among healthcare professionals. Future studies are needed to gain more insight in underlying factors of fatigue in non-communicable chronic diseases, its impact on daily life and development and evaluation of targeted treatment strategies.Key messages:Both physical and mental fatigue are frequently present in people with non-communicable chronic diseases.Fatigue is often only occasionally or never discussed during consultation with the physician, highlighting the need to raise awareness among healthcare professionals for adequate screening and evaluating of fatigue in people with non-communicable chronic diseases.Only less than a quarter of the people with non-communicable chronic diseases who reported to experience fatigue were prescribed a treatment for fatigue, which was often experienced as ineffective

Cognitive performance in relation to metabolic disturbances in patients with COPD

BACKGROUND & AIMS: Cognitive impairment (CI) and metabolic abnormalities, including the metabolic syndrome (MetS) and sarcopenia, are more prevalent in COPD patients compared to controls without diagnosed lung disease. Because earlier studies have shown these metabolic abnormalities may affect cognitive performance, this study investigated whether cognitive performance is more impaired in subgroups of COPD patients with MetS or sarcopenia. METHODS: Cognitive performance patterns of 170 COPD patients referred for pulmonary rehabilitation (53.5% male, 63.4 ± 9.4 years, FEV1 54.5 ± 22.7% predicted) were compared between COPD subgroups stratified by presence of MetS and sarcopenia. Cognitive performance was assessed using a detailed neuropsychological test battery, which measured psychomotor speed (Stroop Color-Word Test, Concept Shifting Test, Letter-Digit Substitution Test), planning (Behavioral Assessment of the Dysexecutive Syndrome), working memory (Visual-Verbal Learning Test, Digit Span), verbal memory (Visual-Verbal Learning Test) and cognitive flexibility (Stroop Color-Word Test, Concept Shifting Test). MetS was determined according to the NCEP ATP-III criteria. Sarcopenia was determined based on decreased appendicular lean mass by dual-energy x-ray absorptiometry and impaired physical performance by 6-min walking distance. RESULTS: MetS was observed in 54.7% and sarcopenia in 30.0% of COPD patients. The prevalence of general CI was not different between patients with and without MetS (30.4% and 39.0%, respectively) or those with and without sarcopenia (34.0% and 34.5%, respectively, both p > 0.05). Domain-specific cognitive performance was not different between metabolic subgroups, but those with sarcopenia displayed a lower prevalence of CI on verbal memory than those without (21.7% and 29.7%, respectively, p = 0.011). Only the digit span (working memory) subtest was significantly different between metabolic subgroups, in favor of those without MetS (p = 0.017). CONCLUSION: Cognitive performance was not affected more in COPD patients with sarcopenia or MetS

Working memory training efficacy in COPD:the randomised, double-blind, placebo-controlled Cogtrain trial

Background: Cognitive impairment is highly prevalent in COPD and is associated with a sedentary lifestyle, unhealthy diet and increased cognitive stress susceptibility. Enhancement of cognitive performance by working memory training (WMT) may reverse these effects. Therefore, this study aimed to investigate the efficacy of WMT in COPD on cognitive performance, healthy lifestyle behaviours and cognitive stress susceptibility. Methods: The double-blind randomised, placebo-controlled Cogtrain trial consisted of a 12-week training phase comprising 30 active or sham WMT sessions, followed by a second 12-week maintenance phase with 12 sessions. Measurements took place at baseline and after the first and second phases. The primary outcome was cognitive performance. Secondary outcomes were the recall of prespecified healthy lifestyle goals, physical capacity and activity, dietary quality and cognitive stress susceptibility. Motivation towards exercising and healthy eating and psychological wellbeing were exploratory outcomes. Results: Sixty-four patients with moderate COPD (45% male, aged 66.2±7.2 years, median forced expiratory volume in 1 s 60.6% predicted) were randomised. WMT significantly increased patients' performance on the trained tasks in the first phase, which remained stable in the second phase. Of the 17 cognitive outcome measures, only one measure of memory improved after the first phase and one measure of reaction time after the second phase. This intervention did not influence physical capacity and activity, recall of prespecified healthy lifestyle goals, psychological wellbeing or cognitive stress susceptibility. Conclusion: WMT improved performance on the trained tasks but not overall cognitive performance, healthy lifestyle behaviours or cognitive stress susceptibility in patients with COPD