Mid-term changes in cognitive functions in patients with atrial fibrillation: a longitudinal analysis of the Swiss-AF cohort

Background: Longitudinal association studies of atrial fibrillation (AF) and cognitive functions have shown an unclear role of AF-type and often differ in methodological aspects. We therefore aim to investigate longitudinal changes in cognitive functions in association with AF-type (non-paroxysmal vs. paroxysmal) and comorbidities in the Swiss-AF cohort. Methods: Seven cognitive measures were administered up to five times between 2014 and 2022. Age-education standardized scores were calculated and association between longitudinal change in scores and baseline AF-type investigated using linear mixed-effects models. Associations between AF-type and time to cognitive drop, an observed score of at least one standard deviation below individual's age-education standardized cognitive scores at baseline, were studied using Cox proportional hazard models of each cognitive test, censoring patients at their last measurement. Models were adjusted for baseline covariates.Results2,415 AF patients (mean age 73.2 years; 1,080 paroxysmal, 1,335 non-paroxysmal AF) participated in this Swiss multicenter prospective cohort study. Mean cognitive scores increased longitudinally (median follow-up 3.97 years). Non-paroxysmal AF patients showed smaller longitudinal increases in Digit Symbol Substitution Test (DSST), Cognitive Construct Score (CoCo)and Trail Making Test part B (TMT-B) scores vs. paroxysmal AF patients. Diabetes, history of stroke/TIA and depression were associated with worse performance on all cognitive tests. No differences in time to cognitive drop were observed between AF-types in any cognitive test. Conclusion: This study indicated preserved cognitive functioning in AF patients, best explained by practice effects. Smaller practice effects were found in non-paroxysmal AF patients in the DSST, TMT-B and the CoCo and could indicate a marker of subtle cognitive decline. As diabetes, history of stroke/TIA and depression—but not AF-type—were associated with cognitive drop, more attention should be given to risk factors and underlying mechanisms of AF

Mid-term changes in cognitive functions in patients with atrial fibrillation: a longitudinal analysis of the Swiss-AF cohort.

BACKGROUND Longitudinal association studies of atrial fibrillation (AF) and cognitive functions have shown an unclear role of AF-type and often differ in methodological aspects. We therefore aim to investigate longitudinal changes in cognitive functions in association with AF-type (non-paroxysmal vs. paroxysmal) and comorbidities in the Swiss-AF cohort. METHODS Seven cognitive measures were administered up to five times between 2014 and 2022. Age-education standardized scores were calculated and association between longitudinal change in scores and baseline AF-type investigated using linear mixed-effects models. Associations between AF-type and time to cognitive drop, an observed score of at least one standard deviation below individual's age-education standardized cognitive scores at baseline, were studied using Cox proportional hazard models of each cognitive test, censoring patients at their last measurement. Models were adjusted for baseline covariates. RESULTS 2,415 AF patients (mean age 73.2 years; 1,080 paroxysmal, 1,335 non-paroxysmal AF) participated in this Swiss multicenter prospective cohort study. Mean cognitive scores increased longitudinally (median follow-up 3.97 years). Non-paroxysmal AF patients showed smaller longitudinal increases in Digit Symbol Substitution Test (DSST), Cognitive Construct Score (CoCo)and Trail Making Test part B (TMT-B) scores vs. paroxysmal AF patients. Diabetes, history of stroke/TIA and depression were associated with worse performance on all cognitive tests. No differences in time to cognitive drop were observed between AF-types in any cognitive test. CONCLUSION This study indicated preserved cognitive functioning in AF patients, best explained by practice effects. Smaller practice effects were found in non-paroxysmal AF patients in the DSST, TMT-B and the CoCo and could indicate a marker of subtle cognitive decline. As diabetes, history of stroke/TIA and depression-but not AF-type-were associated with cognitive drop, more attention should be given to risk factors and underlying mechanisms of AF

Brain Plasticity Induced by Motor and Cognitive Interventions in Health and Pathology

Plasticity, the way the brain can adapt to environmental or intrinsic changes, is the cornerstone of human behavior. Plasticity does not only harbor the possibility to learn or improve new motor or cognitive skills, but also displays the basis for restoring functioning after brain damage. Brain plasticity can thus be induced by various activities and is most prominently investigated following interventions with the aim to enhance cognition in the healthy population or rehabilitative strategies of motor and cognitive functions in pathological conditions. Although it is widely acknowledged that plastic changes are possible after activitydependent interventions, improvements on untrained functional domains are still not fully comprehended. Furthermore, the previous focus on establishing the efficacy has shifted towards the understanding of behavioral and functional underlying mechanisms of interventions. Three studies presented within the frame of this thesis aimed at investigating mechanisms of brain plasticity in health and pathology induced by rehabilitative, motor and cognitive interventions. In the first study (Zuber et al., 2020), we examined the efficacy in symptom improvement and underlying brain mechanisms of an inpatient personalized multidisciplinary rehabilitation program in patients with multiple sclerosis using functional Magnetic Resonance Imaging (fMRI). The multidisciplinary rehabilitation led to improved fatigue, walking ability as well as quality of life and a more effective recruitment of cerebellar and prefrontal brain regions in patients with multiple sclerosis. Two studies in healthy participants aimed at targeting current challenges in the cognitive training research by studying underlying cognitive and motor mechanisms of working memory training. In study B (Zuber, Geiter, de Quervain, & Magon, 2021), we compared a novel model-based working memory training with and without distractor inhibition to a dual-n-back and active control training in order to study distractor inhibition as a task-related process with the potential to render near and far transfer effects in healthy elderly adults. Working memory capacity was improved only following the model-based training with distractor inhibition, suggesting the novel training to be a promising approach in improving working memory in healthy old adults. In study C (Zuber, Gaetano, et al., 2021), we studied the interactive and additive effects of working memory and motor sequence learning training behaviorally and by resting state functional connectivity. Results indicate a relevance of the sequential order of training performance, with increased functional connectivity between a complex network of parietal, temporal and motor brain regions, specifically when motor training was performed before or combined with working memory training. The results of those three studies indicate plastic changes following rehabilitation in patients with multiple sclerosis and motor and cognitive interventions in healthy people. It can thus be concluded that brain plasticity following interventions in health and pathology is the result of an interplay between various behavioral and functional mechanisms. Hence, this thesis highlights the importance of identifying underlying neural and behavioral processes by theory-driven approaches in methodologically well controlled studies as the basis for translating neuroscientific research into the clinical setting

Investigation of a Model-Based Working Memory Training With and Without Distractor Inhibition and Its Comparative Efficacy: A Randomized Controlled Trial on Healthy Old Adults

Background; : Various working memory (WM) trainings have been tested, but differences in experimental designs, the lack of theoretical background, and the need of identifying task-related processes such as filtering efficiency limit conclusions about their comparative efficacy.; Objectives; : In this study, we compared the efficacy of a model-based WM training with (MB; +; ) and without (MB) distractor inhibition on improving WM capacity to a dual; n-back; and active control condition.; Methods; : This randomized clinical trial included 123 healthy elderly adults (78 women, 45 men; aged 64.1 ± 8.3 years). All groups underwent 12 40-min training sessions over 3 weeks and four cognitive testing sessions. The first two sessions served as double baseline to account for practice effects. Primary outcome was WM capacity post-training measured by complex span tasks. Near and far transfer was assessed by simple span, n-back, visuospatial and verbal learning, processing speed, and reasoning tasks.; Results; : Due to preliminary termination (COVID-19), 93 subjects completed the post-training and 60 subjects the follow-up session. On a whole group level, practice effects occurred from prebaseline to baseline in WM capacity (; b; = 4.85,; t; (103); = 4.01,; p; < 0.001,; r; = 0.37). Linear mixed-effects models revealed a difference in WM capacity post-training between MB; +; and MB (; b; = -9.62,; t; (82); = -2.52,; p; = 0.014,; r; = 0.27) and a trend difference between MB; +; and dual; n-back; (; b; = -7.59,; t; (82); = -1.87,; p; = 0.065,; r; = 0.20) and control training (; b; = -7.08,; t; (82); = -1.86,; p; = 0.067,; r; = 0.20). Univariate analyses showed an increase between pre- and post-training for WM capacity within MB; +; (; t; (22); = -3.34,; p; < 0.05) only. There was no difference between groups pre- and post-training regarding near and far transfer. Univariate analyses showed improved visuospatial learning within MB; +; (; t; (21); = -3.8,; p; < 0.05), improved processing speed (; t; (23); = 2.19,; p; < 0.05) and; n; -back performance (; t; (23); = 2.12,; p; < 0.05) in MB, and improved; n; -back performance (; t; (25); = 3.83,; p; < 0.001) in the dual; n; -back training.; Interpretation; : A model-based WM training including filtering efficacy may be a promising approach to increase WM capacity and needs further investigation in randomized controlled studies

The Swiss Corona Stress Study: second pandemic wave, November 2020

The results of the third survey of the Swiss Corona Stress Study refer to the period from November 11-19, 2020, during which 11,612 people from all over Switzerland participated. Stress levels have increased significantly compared to the first survey during lockdown in April 2020. While the proportion of people reporting maximum stress levels was around 11% during the April lockdown, it rose to 20% in the second pandemic wave in November. The increase in stress was accompanied by an increase in depressive symptoms. The main drivers of psychological stress and depressive symptoms included burden due to a Covid-19-related change in work, school, or education, Covid-19-related financial losses, and fears about the future. These stressors have increased significantly, compared to the time of the April lockdown. Further factors were the fear that someone in the closest circle would become seriously ill or die from COVID-19, as well as the burden of social restrictions and burden from an increase in conflicts at home. While the proportion of respondents with moderately severe or severe (PHQ-9 ≥15) depressive symptoms was 3% before the pandemic, 9% during the April lockdown, and 12% during May, it increased to 18% in November. The risk for moderately severe or severe depressive symptoms was associated with age (with younger people showing the highest risk) and was increased in people experiencing financial losses due to the pandemic. In addition, people from the French-speaking part of Switzerland, which was most affected by the pandemic during the second wave, were at higher risk than people from the rest of Switzerland

The Swiss Corona Stress Study

The mental consequences of the COVID-19 pandemic and the strict lockdown measures implemented by governments world-wide to fight it are currently unknown. We performed an online survey study in Switzerland and analyzed data acquired during confinement (wave 1) and during partial lifting of measures (partial deconfinement) (wave 2). Wave 1: Data from over 10’000 individuals living in Switzerland were collected between April 6 and 8, 2020, starting 3 weeks after the beginning of confinement. While 24.4% of the participants reported no change in stress levels, 49.6% of the participants reported an increase in stress levels during confinement as compared to the time before the COVID-19 pandemic. We identified several potential sources for people feeling more stressed during confinement, such as the burden related to changes at work or school, problems with childcare or not being able to spend more time with others. The changes in stress levels were highly correlated with changes in depressive symptoms. 57% of the participants reported an increase in depressive symptoms. Further, the prevalence of moderately severe or severe depressive symptoms (PHQ-9 score ≥ 15) increased from 3.4% before the COVID-19 pandemic to 9.1% during confinement. Interestingly, 26% of participants showed a decrease in stress level during confinement, suggesting that for those individuals the confinement involved a reduction of stressors and/or resulted in more time for recovery. Finally, we identified several behaviors amenable to change that were related to a reduced increase in stress level and depressive symptoms during confinement. Wave 2: Data from over 10’000 individuals living in Switzerland were collected between May 11 and June 1, 2020 during partial deconfinement. As for wave 1, we observed diverse reactions with regard to stress levels: While 28% of the participants reported no change in stress levels, 40% of the participants reported an increase in stress levels during partial deconfinement as compared to the time before the COVID-19 pandemic. We identified similar sources for people feeling more stressed as during confinement and the changes in stress levels were highly correlated with changes in depressive symptoms. 49.5% of the participants reported an increase in depressive symptoms. Further, the prevalence of moderately severe or severe depressive symptoms (PHQ-9 score ≥ 15) remained elevated with a prevalence rate of 11.7%. With regard to changeable behaviors during the pandemic, we found (as in wave 1) that spending more time pursuing new projects, spending more time pursuing hobbies at home, and light physical exercise were related to less stress increase. A comparison between the two waves indicated that while the waves did not substantially differ in the distributions of changes in stress levels or depressive symptoms, they did differ with regard to the distribution of anxiety ratings. Specifically, anxiety levels decreased from wave 1 to wave 2. Finally, we identified risk and resilience factors with regard to the development of depressive symptoms (present in both waves): A history of a prior psychiatric disorder was a risk factor for developing moderately severe or severe depressive symptoms during the pandemic. In a resilient group of people who had none or only minimal depressive symptoms before and during the pandemic, older people (≥ 55 years), men and individuals with no history of prior psychiatric disorder were overrepresented. Thus, advanced age, male gender and the absence of prior psychiatric disorder were identified as resilience factors