TY - JOUR A1 - Heinzel, Stephan A1 - Lorenz, Robert C. A1 - Quynh-Lam Duong, A1 - Rapp, Michael A. A1 - Deserno, Lorenz T1 - Prefrontal-parietal effective connectivity during working memory in older adults JF - Neurobiology of Aging N2 - Theoretical models and preceding studies have described age-related alterations in neuronal activation of frontoparietal regions in a working memory (WM)load-dependent manner. However, to date, underlying neuronal mechanisms of these WM load-dependent activation changes in aging remain poorly understood. The aim of this study was to investigate these mechanisms in terms of effective connectivity by application of dynamic causal modeling with Bayesian Model Selection. Eighteen healthy younger (age: 20-32 years) and 32 older (60-75 years) participants performed an n-back task with 3 WM load levels during functional magnetic resonance imaging (fMRI). Behavioral and conventional fMRI results replicated age group by WM load interactions. Importantly, the analysis of effective connectivity derived from dynamic causal modeling, indicated an age-and performance-related reduction in WM load-dependent modulation of connectivity from dorsolateral prefrontal cortex to inferior parietal lobule. This finding provides evidence for the proposal that age-related WM decline manifests as deficient WM load-dependent modulation of neuronal top-down control and can integrate implications from theoretical models and previous studies of functional changes in the aging brain. KW - Aging KW - Dynamic causal modeling (DCM) KW - Effective connectivity KW - Functional magnetic resonance imaging (fMRI) KW - Working memory Y1 - 2017 U6 - https://doi.org/10.1016/j.neurobiolaging.2017.05.005 SN - 0197-4580 SN - 1558-1497 VL - 57 SP - 18 EP - 27 PB - Elsevier CY - New York ER - TY - JOUR A1 - Heinzel, Stephan A1 - Rimpel, Jérôme A1 - Stelzel, Christine A1 - Rapp, Michael A. T1 - Transfer Effects to a Multimodal Dual-Task after Working Memory Training and Associated Neural Correlates in Older Adults BT - A Pilot Study JF - Frontiers in human neuroscience N2 - Working memory (WM) performance declines with age. However, several studies have shown that WM training may lead to performance increases not only in the trained task, but also in untrained cognitive transfer tasks. It has been suggested that transfer effects occur if training task and transfer task share specific processing components that are supposedly processed in the same brain areas. In the current study, we investigated whether single-task WM training and training-related alterations in neural activity might support performance in a dual-task setting, thus assessing transfer effects to higher-order control processes in the context of dual-task coordination. A sample of older adults (age 60–72) was assigned to either a training or control group. The training group participated in 12 sessions of an adaptive n-back training. At pre and post-measurement, a multimodal dual-task was performed in all participants to assess transfer effects. This task consisted of two simultaneous delayed match to sample WM tasks using two different stimulus modalities (visual and auditory) that were performed either in isolation (single-task) or in conjunction (dual-task). A subgroup also participated in functional magnetic resonance imaging (fMRI) during the performance of the n-back task before and after training. While no transfer to single-task performance was found, dual-task costs in both the visual modality (p < 0.05) and the auditory modality (p < 0.05) decreased at post-measurement in the training but not in the control group. In the fMRI subgroup of the training participants, neural activity changes in left dorsolateral prefrontal cortex (DLPFC) during one-back predicted post-training auditory dual-task costs, while neural activity changes in right DLPFC during three-back predicted visual dual-task costs. Results might indicate an improvement in central executive processing that could facilitate both WM and dual-task coordination. KW - working memory KW - cognitive training KW - modality KW - dual-task KW - aging KW - transfer KW - fMRI KW - neuroimaging Y1 - 2017 U6 - https://doi.org/10.3389/fnhum.2017.00085 VL - 11 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Jacob, Louis A1 - Rapp, Michael A. A1 - Kostev, Karel T1 - Long-term use of benzodiazepines in older patients in Germany BT - a retrospective analysis JF - Therapeutic Advances in Psychopharmacology N2 - Background: The purpose of this study was to analyze the prevalence of long-term benzodiazepine use in older adults treated in general and neuropsychiatric practices in Germany. Methods: This study included 32,182 patients over the age of 65 years who received benzodiazepine prescriptions for the first time between January 2010 and December 2014 in general and neuropsychiatric practices in Germany. Follow up lasted until July 2016. The main outcome measure was the proportion of patients treated with benzodiazepines for >6 months. Results: The proportion of patients with benzodiazepine therapy for >6 months increased with age (65-70 years: 12.3%; 71-80 years: 15.5%; 81-90 years: 23.7%; >90 years: 31.6%) but did not differ significantly between men (15.5%) and women (17.1%). The proportion of patients who received benzodiazepines for >6 months was higher among those with sleep disorders (21.1%), depression (20.8%) and dementia (32.1%) than among those with anxiety (15.5%). By contrast, this proportion was lower among people diagnosed with adjustment disorders (7.7%) and back pain (3.8%). Conclusion: Overall, long-term use of benzodiazepines is common in older people, particularly in patients over the age of 80 and in those diagnosed with dementia, sleep disorders, or depression. KW - benzodiazepines KW - Germany KW - long-term use KW - older people KW - risk factors Y1 - 2017 U6 - https://doi.org/10.1177/2045125317696454 SN - 2045-1253 SN - 2045-1261 VL - 7 IS - 6/7 SP - 191 EP - 200 PB - Sage Publ. CY - London ER - TY - JOUR A1 - Kallies, Gunnar A1 - Rapp, Michael A. A1 - Fydrich, Thomas A1 - Fehm, Lydia A1 - Tschorn, Mira A1 - Teran, Christina A1 - Schwefel, Melanie A1 - Pietrek, Anou F. A1 - Henze, Romy A1 - Hellweg, Rainer A1 - Ströhle, Andreas A1 - Heinzel, Stephan A1 - Heissel, Andreas T1 - Serum brain-derived neurotrophic factor (BDNF) at rest and after acute aerobic exercise in major depressive disorder JF - Psychoneuroendocrinology N2 - Physiological mechanisms of an anti-depressive effect of physical exercise in major depressive disorder (MDD) seem to involve alterations in brain-derived neurotrophic factor (BDNF) level. However, previous studies which investigated this effect in a single bout of exercise, did not control for confounding peripheral factors that contribute to BDNF-alterations. Therefore, the underlying cause of exercise-induced BDNF-changes remains unclear. The current study aims to investigate serum BDNF (sBDNF)-changes due to a single-bout of graded aerobic exercise in a group of 30 outpatients with MDD, suggesting a more precise analysis method by taking plasma volume shift and number of platelets into account. Results show that exercise-induced increases in sBDNF remain significant (p<.001) when adjusting for plasma volume shift and controlling for number of platelets. The interaction of sBDNF change and number of platelets was also significant (p=.001) indicating larger sBDNF-increase in participants with smaller number of platelets. Thus, findings of this study suggest an involvement of peripheral as well as additional possibly brain-derived mechanisms explaining exercise-related BDNF release in MDD. For future studies in the field of exercise-related BDNF research, the importance of controlling for peripheral parameters is emphasized. KW - Brain-derived neurotrophic factor (BDNF) KW - Platelets KW - Major depressive disorder KW - Physical exercise Y1 - 2018 U6 - https://doi.org/10.1016/j.psyneuen.2018.12.015 SN - 0306-4530 VL - 102 SP - 212 EP - 215 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Meiberth, Dix Urs A1 - Rapp, Michael A. A1 - Jessen, Frank T1 - Gedächtnisambulanzstrukturen in Deutschland – Ergebnisse einer Klinikbefragung JF - Psychiatrische Praxis N2 - Ziel der Studie Erfassung der Strukturen zur Frühdiagnostik von Demenzen an Krankenhäusern in Deutschland. Methodik Fragebogenerhebung. Ergebnisse 14 % von 1758 kontaktierten Einrichtungen antworteten. 52 % berichteten über ein entsprechendes Angebot, zum großen Teil mit leitlinienorientierten Verfahren, wie Liquordiagnostik. Das Diagnosespektrum umfasste zu 46 % Demenzen und zu 41 % Diagnosen der leichten oder subjektiven kognitiven Störung. Schlussfolgerung Leitlinienbasierte Diagnostik und Früherkennungskonzepte sind in Gedächtnisambulanzen weitgehend etabliert. N2 - Objective To assess the structures for early and differential diagnosis of dementia in hospitals in Germany. Methods Written questionnaire to all German hospitals. Results 14 % of 1.758 hospitals responded. Of those, 52 % reported to offer a special service for early dementia diagnosis, mostly on an outpatient basis. The applied methods were in agreement with the national guideline for diagnosis and treatment of dementias, including technical diagnostics, such as neuroimaging and cerebrospinal fluid examinations. 46 % of the diagnostic spectrum were dementia. 41 % were either diagnosed as mild cognitive impairment (MCI) or as subjective cognitive decline (SCD). Conclusion Despite mostly insufficient reimbursement, a large proportion of the responding hospitals offer a specialized service, which largely adheres to guideline-based diagnostic procedures. The concepts of at-risk and prodromal stages of dementia seem to be largely established. T2 - Memory Clinics in Germany - Results of a Hospital Survey KW - dementia KW - Alzheimer KW - memory clinic KW - early diagnosis KW - Demenz KW - Alzheimer KW - Gedächtnisambulanz KW - Frühdiagnose Y1 - 2019 U6 - https://doi.org/10.1055/a-0825-9049 SN - 0303-4259 SN - 1439-0876 VL - 46 IS - 4 SP - 213 EP - 216 PB - Thieme CY - Stuttgart ER - TY - JOUR A1 - Sebold, Miriam A1 - Spitta, G. A1 - Gleich, T. A1 - Dembler-Stamm, T. A1 - Butler, Oisin A1 - Zacharias, Kristin A1 - Aydin, S. A1 - Garbusow, Maria A1 - Rapp, Michael A. A1 - Schubert, Florian A1 - Buchert, Ralph A1 - Gallinat, Jürgen A1 - Heinz, A. T1 - Stressful life events are associated with striatal dopamine receptor availability in alcohol dependence JF - Journal of neural transmission N2 - Stress plays a key role in modulating addictive behavior and can cause relapse following periods of abstinence. Common effects of stress and alcohol on the dopaminergic system have been suggested, although the precise mechanisms are unclear. Here, we investigated 20 detoxified alcohol-dependent patients and 19 matched healthy controls and assessed striatal D2/D3 availability using [F-18]-fallypride positron emission tomography and stressful life events. We found a strong association between striatal D2/D3 availability and stress in patients, but not in healthy controls. Interestingly, we found increased D2/D3 receptor availability in patients with higher stress levels. This mirrors complex interactions between stress and alcohol intake in animal studies and emphasizes the importance to investigate stress exposure in neurobiological studies of addiction. KW - Stressful life events KW - Dopamine D2 KW - D3 receptor KW - Positron emission tomography KW - Striatum KW - Alcohol dependence Y1 - 2019 U6 - https://doi.org/10.1007/s00702-019-01985-2 SN - 0300-9564 SN - 1435-1463 VL - 126 IS - 9 SP - 1127 EP - 1134 PB - Springer CY - Wien ER - TY - JOUR A1 - Bohlken, Jens A1 - Weber, Simon A. A1 - Siebert, Anke A1 - Forstmeier, Simon A1 - Kohlmann, Thomas A1 - Rapp, Michael A. T1 - Reminiscence therapy for depression in dementia BT - An observational study with matched pairs JF - GeroPsych - The Journal of gerontopsychology and geriatric psychiatry N2 - We investigated the efficacy of reminiscence therapy (RT) on symptoms of depression in patients with mild to moderate dementia. Out of 227 patients with mild to moderate dementia from a specialized physician’s office, 27 pairs (N = 54; mean age 79.04 ± 6.16 years) who had either received treatment as usual (TAU) or TAU combined with RT, were matched retrospectively according to age as well as cognitive and depressive symptom scores. After controlling for age and sex, symptoms of depression significantly decreased over time in the RT group compared to TAU (F1,52 = 4.36; p < .05). RT is a promising option for the treatment of depression in mild to moderate dementia. Larger randomized-controlled trials are needed. KW - reminiscence KW - life story book Y1 - 2017 U6 - https://doi.org/10.1024/1662-9647/a000175 SN - 1662-9647 SN - 1662-971X VL - 30 SP - 145 EP - 151 PB - Hogrefe CY - Göttingen ER - TY - JOUR A1 - Tschorn, Mira A1 - Schulze, Susanne A1 - Förstner, Bernd Rainer A1 - Holmberg, Christine A1 - Spallek, Jacob A1 - Heinz, Andreas A1 - Rapp, Michael A. T1 - Predictors and prevalence of hazardous alcohol use in middle-late to late adulthood in Europe JF - Aging & mental health N2 - Objectives: Even low to moderate levels of alcohol consumption can have detrimental health consequences, especially in older adults (OA). Although many studies report an increase in the proportion of drinkers among OA, there are regional variations. Therefore, we examined alcohol consumption and the prevalence of hazardous alcohol use (HAU) among men and women aged 50+ years in four European regions and investigated predictors of HAU. Methods: We analyzed data of N = 35,042 participants of the European SHARE study. We investigated differences in alcohol consumption (units last week) according to gender, age and EU-region using ANOVAs. Furthermore, logistic regression models were used to examine the effect of income, education, marital status, history of a low-quality parent-child relationship and smoking on HAU, also stratified for gender and EU-region. HAU was operationalized as binge drinking or risky drinking (<12.5 units of 10 ml alcohol/week). Results: Overall, past week alcohol consumption was 5.0 units (+/- 7.8), prevalence of HAU was 25.4% within our sample of European adults aged 50+ years. Male gender, younger age and living in Western Europe were linked to both higher alcohol consumption and higher risks of HAU. Income, education, smoking, a low-quality parent-child relationship, living in Northern and especially Eastern Europe were positively associated with HAU. Stratified analyses revealed differences by region and gender. Conclusions: HAU was highly prevalent within this European sample of OA. Alcohol consumption and determinants of HAU differed between EU-regions, hinting to a necessity of risk-stratified population-level strategies to prevent HAU and subsequent alcohol use disorders. KW - Hazardous alcohol use KW - older adults KW - middle-aged adults KW - Europe KW - alcohol KW - drug and alcohol abuse KW - cross-national KW - international studies KW - environmental factors KW - housing KW - rural-urban factors KW - epidemiology (mental health) Y1 - 2022 U6 - https://doi.org/10.1080/13607863.2022.2076208 SN - 1360-7863 SN - 1364-6915 VL - 27 IS - 5 SP - 1001 EP - 1010 PB - Routledge, Taylor & Francis Group CY - Abingdon ER - TY - JOUR A1 - Garbusow, Maria A1 - Ebrahimi, Claudia A1 - Riemerschmid, Carlotta A1 - Daldrup, Luisa A1 - Rothkirch, Marcus A1 - Chen, Ke A1 - Chen, Hao A1 - Belanger, Matthew J. A1 - Hentschel, Angela A1 - Smolka, Michael A1 - Heinz, Andreas A1 - Pilhatsch, Maximilan A1 - Rapp, Michael A. T1 - Pavlovian-to-instrumental transfer across mental disorders BT - a review JF - Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography N2 - A mechanism known as Pavlovian-to-instrumental transfer (PIT) describes a phenomenon by which the values of environmental cues acquired through Pavlovian conditioning can motivate instrumental behavior. PIT may be one basic mechanism of action control that can characterize mental disorders on a dimensional level beyond current classification systems. Therefore, we review human PIT studies investigating subclinical and clinical mental syndromes. The literature prevails an inhomogeneous picture concerning PIT. While enhanced PIT effects seem to be present in non-substance-related disorders, overweight people, and most studies with AUD patients, no altered PIT effects were reported in tobacco use disorder and obesity. Regarding AUD and relapsing alcohol-dependent patients, there is mixed evidence of enhanced or no PIT effects. Additionally, there is evidence for aberrant corticostriatal activation and genetic risk, e.g., in association with high-risk alcohol consumption and relapse after alcohol detoxification. In patients with anorexia nervosa, stronger PIT effects elicited by low caloric stimuli were associated with increased disease severity. In patients with depression, enhanced aversive PIT effects and a loss of action-specificity associated with poorer treatment outcomes were reported. Schizophrenic patients showed disrupted specific but intact general PIT effects. Patients with chronic back pain showed reduced PIT effects. We provide possible reasons to understand heterogeneity in PIT effects within and across mental disorders. Further, we strengthen the importance of reliable experimental tasks and provide test-retest data of a PIT task showing moderate to good reliability. Finally, we point toward stress as a possible underlying factor that may explain stronger PIT effects in mental disorders, as there is some evidence that stress per se interacts with the impact of environmental cues on behavior by selectively increasing cue-triggered wanting. To conclude, we discuss the results of the literature review in the light of Research Domain Criteria, suggesting future studies that comprehensively assess PIT across psychopathological dimensions. KW - Pavlovian-to-instrumental transfer KW - dimensional psychopathology KW - mental disorders KW - reliability Y1 - 2022 U6 - https://doi.org/10.1159/000525579 SN - 0302-282X SN - 1423-0224 VL - 81 IS - 5 SP - 418 EP - 437 PB - Karger CY - Basel ER - TY - JOUR A1 - Sebold, Miriam A1 - Chen, Hao A1 - Önal, Aleyna A1 - Kuitunen-Paul, Sören A1 - Mojtahedzadeh, Negin A1 - Garbusow, Maria A1 - Nebe, Stephan A1 - Wittchen, Hans-Ulrich A1 - Huys, Quentin J. M. A1 - Schlagenhauf, Florian A1 - Rapp, Michael A. A1 - Smolka, Michael N. A1 - Heinz, Andreas T1 - Stronger prejudices are associated with decreased model-based control JF - Frontiers in psychology N2 - Background: Prejudices against minorities can be understood as habitually negative evaluations that are kept in spite of evidence to the contrary. Therefore, individuals with strong prejudices might be dominated by habitual or "automatic" reactions at the expense of more controlled reactions. Computational theories suggest individual differences in the balance between habitual/model-free and deliberative/model-based decision-making. Methods: 127 subjects performed the two Step task and completed the blatant and subtle prejudice scale. Results: By using analyses of choices and reaction times in combination with computational modeling, subjects with stronger blatant prejudices showed a shift away from model-based control. There was no association between these decision-making processes and subtle prejudices. Conclusion: These results support the idea that blatant prejudices toward minorities are related to a relative dominance of habitual decision-making. This finding has important implications for developing interventions that target to change prejudices across societies. KW - subtle and blatant prejudice KW - immigrant KW - social behavior; KW - decision-making KW - computational modeling KW - reinforcement learning Y1 - 2022 U6 - https://doi.org/10.3389/fpsyg.2021.767022 SN - 1664-1078 VL - 12 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Förstner, Bernd R. A1 - Tschorn, Mira A1 - Reinoso-Schiller, Nicolas A1 - Maričić, Lea Mascarell A1 - Röcher, Erik A1 - Kalman, Janos L. A1 - Stroth, Sanna A1 - Mayer, Annalina V. A1 - Schwarz, Kristina A1 - Kaiser, Anna A1 - Pfennig, Andrea A1 - Manook, André A1 - Ising, Marcus A1 - Heinig, Ingmar A1 - Pittig, Andre A1 - Heinz, Andreas A1 - Mathiak, Klaus A1 - Schulze, Thomas G. A1 - Schneider, Frank A1 - Kamp-Becker, Inge A1 - Meyer-Lindenberg, Andreas A1 - Padberg, Frank A1 - Banaschewski, Tobias A1 - Bauer, Michael A1 - Rupprecht, Rainer A1 - Wittchen, Hans-Ulrich A1 - Rapp, Michael A. T1 - Mapping research domain criteria using a transdiagnostic mini-RDoC assessment in mental disorders: a confirmatory factor analysis JF - European archives of psychiatry and clinical neuroscience N2 - This study aimed to build on the relationship of well-established self-report and behavioral assessments to the latent constructs positive (PVS) and negative valence systems (NVS), cognitive systems (CS), and social processes (SP) of the Research Domain Criteria (RDoC) framework in a large transnosological population which cuts across DSM/ICD-10 disorder criteria categories. One thousand four hundred and thirty one participants (42.1% suffering from anxiety/fear-related, 18.2% from depressive, 7.9% from schizophrenia spectrum, 7.5% from bipolar, 3.4% from autism spectrum, 2.2% from other disorders, 18.4% healthy controls, and 0.2% with no diagnosis specified) recruited in studies within the German research network for mental disorders for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) were examined with a Mini-RDoC-Assessment including behavioral and self-report measures. The respective data was analyzed with confirmatory factor analysis (CFA) to delineate the underlying latent RDoC-structure. A revised four-factor model reflecting the core domains positive and negative valence systems as well as cognitive systems and social processes showed a good fit across this sample and showed significantly better fit compared to a one factor solution. The connections between the domains PVS, NVS and SP could be substantiated, indicating a universal latent structure spanning across known nosological entities. This study is the first to give an impression on the latent structure and intercorrelations between four core Research Domain Criteria in a transnosological sample. We emphasize the possibility of using already existing and well validated self-report and behavioral measurements to capture aspects of the latent structure informed by the RDoC matrix. KW - Diagnosis and classification KW - Research Domain Criteria KW - PD-CAN KW - Confirmatory factor analysis CFA KW - RDoC KW - Transdiagnostic Y1 - 2022 U6 - https://doi.org/10.1007/s00406-022-01440-6 SN - 0940-1334 SN - 1433-8491 VL - 273 IS - 3 SP - 527 EP - 539 PB - Springer Nature CY - Heidelberg ER - TY - JOUR A1 - Zech, Hilmar G. A1 - Reichert, Markus A1 - Ebner-Priemer, Ulrich W. A1 - Tost, Heike A1 - Rapp, Michael A. A1 - Heinz, Andreas A1 - Dolan, Raymond J. A1 - Smolka, Michael N. A1 - Deserno, Lorenz T1 - Mobile data collection of cognitive-behavioral tasks in substance use disorders: Where are we now? JF - Neuropsychobiology N2 - Introduction: Over the last decades, our understanding of the cognitive, motivational, and neural processes involved in addictive behavior has increased enormously. A plethora of laboratory-based and cross-sectional studies has linked cognitive-behavioral measures to between-subject differences in drinking behavior. However, such laboratory-based studies inevitably suffer from small sample sizes and the inability to link temporal fluctuations in task measures to fluctuations in real-life substance use. To overcome these problems, several existing behavioral tasks have been transferred to smartphones to allow studying cognition in the field. Method: In this narrative review, we first summarize studies that used existing behavioral tasks in the laboratory and self-reports of substance use with ecological momentary assessment (EMA) in the field. Next, we review studies on psychometric properties of smartphone-based behavioral tasks. Finally, we review studies that used both smartphone-based tasks and self-reports with EMA in the field. Results: Overall, studies were scarce and heterogenous both in tasks and in study outcomes. Nevertheless, existing findings are promising and point toward several methodological recommendations: concerning psychometrics, studies show that - although more systematic studies are necessary - task validity and reliability can be improved, for example, by analyzing several measurement sessions at once rather than analyzing sessions separately. Studies that use tasks in the field, moreover, show that power can be improved by choosing sampling schemes that combine time-based with event-based sampling, rather than relying on time-based sampling alone. Increasing sampling frequency can further increase power. However, as this also increases the burden to participants, more research is necessary to determine the ideal sampling frequency for each task. Conclusion: Although more research is necessary to systematically study both the psychometrics of smartphone-based tasks and the frequency at which task measures fluctuate, existing studies are promising and reveal important methodological recommendations useful for researchers interested in implementing behavioral tasks in EMA studies. KW - Ecological momentary assessment KW - Behavioral tasks KW - Smartphone KW - Substance use KW - Addiction Y1 - 2022 U6 - https://doi.org/10.1159/000523697 SN - 0302-282X SN - 1423-0224 VL - 81 IS - 5 SP - 438 EP - 450 PB - Karger CY - Basel ER - TY - JOUR A1 - Herrmann, Matthias L. A1 - Boden, Cindy A1 - Maurer, Christoph A1 - Kentischer, Felix A1 - Mennig, Eva A1 - Wagner, Sören A1 - Conzelmann, Lars O. A1 - Förstner, Bernd R. A1 - Rapp, Michael A. A1 - von Arnim, Christine A. F. A1 - Denkinger, Michael A1 - Eschweiler, Gerhard W. A1 - Thomas, Christine T1 - Anticholinergic drug exposure increases the risk of delirium in older patients undergoing elective surgery JF - Frontiers in medicine N2 - IntroductionPostoperative delirium (POD) is a common and serious adverse event of surgery in older people. Because of its great impact on patients' safety and quality of life, identification of modifiable risk factors could be useful. Although preoperative medication intake is assumed to be an important modifiable risk factor, the impact of anticholinergic drugs on the occurrence of POD seems underestimated in elective surgery. The aim of this study was to investigate the association between preoperative anticholinergic burden and POD. We hypothesized that a high preoperative anticholinergic burden is an independent, potentially modifiable predisposing and precipitating factor of POD in older people. MethodsBetween November 2017 and April 2019, 1,470 patients of 70 years and older undergoing elective orthopedic, general, cardiac, or vascular surgery were recruited in the randomized, prospective, multicenter PAWEL trial. Anticholinergic burden of a sub-cohort of 899 patients, who did not receive a multimodal intervention for preventing POD, was assessed by two different tools at hospital admission: The established Anticholinergic Risk Scale (ARS) and the recently developed Anticholinergic Burden Score (ABS). POD was detected by confusion assessment method (CAM) and a validated post discharge medical record review. Logistic regression analyses were performed to evaluate the association between anticholinergic burden and POD. ResultsPOD was observed in 210 of 899 patients (23.4%). Both ARS and ABS were independently associated with POD. The association persisted after adjustment for relevant confounding factors such as age, sex, comorbidities, preoperative cognitive and physical status, number of prescribed drugs, surgery time, type of surgery and anesthesia, usage of heart-lung-machine, and treatment in intensive care unit. If a patient was taking one of the 56 drugs listed in the ABS, risk for POD was 2.7-fold higher (OR = 2.74, 95% CI = 1.55-4.94) and 1.5-fold higher per additional point on the ARS (OR = 1.54, 95% CI = 1.15-2.02). ConclusionPreoperative anticholinergic drug exposure measured by ARS or ABS was independently associated with POD in older patients undergoing elective surgery. Therefore, identification, discontinuation or substitution of anticholinergic medication prior to surgery may be a promising approach to reduce the risk of POD in older patients. KW - delirium KW - acute encephalopathy KW - surgery KW - anticholinergic KW - geriatric KW - postoperative Y1 - 2022 U6 - https://doi.org/10.3389/fmed.2022.871229 SN - 2296-858X VL - 9 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Sebold, Miriam A1 - Nebe, Stephan A1 - Garbusow, Maria A1 - Guggenmos, Matthias A1 - Schad, Daniel A1 - Beck, Anne A1 - Kuitunen-Paul, Sören A1 - Sommer, Christian A1 - Frank, Robin A1 - Neu, Peter A1 - Zimmermann, Ulrich S. A1 - Rapp, Michael A. A1 - Smolka, Michael N. A1 - Huys, Quentin J. M. A1 - Schlagenhauf, Florian A1 - Heinz, Andreas T1 - When Habits Are Dangerous: Alcohol Expectancies and Habitual Decision Making Predict Relapse in Alcohol Dependence JF - Biological psychiatry : a journal of psychiatric neuroscience and therapeutics ; a publication of the Society of Biological Psychiatry N2 - BACKGROUND: Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. METHODS: Ninety detoxified, medication-free, alcohol-dependent patients and 96 age-and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. RESULTS: Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. CONCLUSIONS: These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies. KW - Alcohol dependence KW - Alcohol expectancy KW - Goal-directed control KW - Medial prefrontal cortex KW - Reinforcement learning KW - Treatment outcome Y1 - 2017 U6 - https://doi.org/10.1016/j.biopsych.2017.04.019 SN - 0006-3223 SN - 1873-2402 VL - 82 SP - 847 EP - 856 PB - Elsevier CY - New York ER - TY - JOUR A1 - Konrad, Marcel A1 - Jacob, Louis A1 - Rapp, Michael A. A1 - Kostev, Karel T1 - Treatment of depression in patients with cardiovascular diseases by German psychiatrists JF - International journal of clinical pharmacology and therapeutics N2 - Objective: To estimate the prevalence and the type of antidepressant medication prescribed by German psychiatrists to patients with depression and cardiovascular diseases (CVD). Methods: This study was a retrospective database analysis in Germany using the Disease Analyzer Database (IMS Health, Germany). The study population included 2,288 CVD patients between 40 and 90 years of age from 175 psychiatric practices. The observation period was between 2004 and 2013. Follow-up lasted up to 12 months and ended in April 2015. Also included were 2,288 non-CVD controls matched (1 : 1) to CVD cases on the basis of age, gender, health insurance coverage, depression severity, and diagnosing physician. Results: Mean age was 68.6 years. 46.2% of patients were men, and 5.9% had private health insurance coverage. Mild, moderate, or severe depression was present in 18.7%, 60.7%, and 20.6% of patients, respectively. Most patients had treatment within a year, many of them immediately after depression diagnosis. Patients with moderate and severe depression were more likely to receive treatment than patients with mild depression. There was no difference between CVD and non-CVD in the proportion of patients treated. Nonetheless, CVD patients received selective serotonin reuptake inhibitors / serotonin-noradrenaline reuptake inhibitors (SSRIs/SNRIs) significantly more frequently. Conversely, patients without CVD were more often treated with TCA. Conclusion: There was no association between CVD and the initiation of depression treatment. Furthermore, CVD patients received SSRIs/SNRIs more frequently. KW - depression KW - cardiovascular diseases KW - antidepressant therapy KW - psychiatric practices Y1 - 2016 U6 - https://doi.org/10.5414/CP202591 SN - 0946-1965 VL - 54 SP - 557 EP - 563 PB - Dustri-Verlag Dr. Karl Feistle CY - Deisenhofen-München ER - TY - JOUR A1 - Garbusow, Maria A1 - Schad, Daniel A1 - Sebold, Miriam A1 - Friedel, Eva A1 - Bernhardt, Nadine A1 - Koch, Stefan P. A1 - Steinacher, Bruno A1 - Kathmann, Norbert A1 - Geurts, Dirk E. M. A1 - Sommer, Christian A1 - Mueller, Dirk K. A1 - Nebe, Stephan A1 - Paul, Soeren A1 - Wittchen, Hans-Ulrich A1 - Zimmermann, Ulrich S. A1 - Walter, Henrik A1 - Smolka, Michael N. A1 - Sterzer, Philipp A1 - Rapp, Michael A. A1 - Huys, Quentin J. M. A1 - Schlagenhauf, Florian A1 - Heinz, Andreas T1 - Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence JF - Addiction biology N2 - In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence. KW - human Pavlovian-to-instrumental transfer KW - nucleus accumbens KW - relapse in alcohol use disorder Y1 - 2016 U6 - https://doi.org/10.1111/adb.12243 SN - 1355-6215 SN - 1369-1600 VL - 21 SP - 719 EP - 731 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Stroehle, Andreas A1 - Schmidt, Dietlinde K. A1 - Schultz, Florian A1 - Fricke, Nina A1 - Staden, Theresa A1 - Hellweg, Rainer A1 - Priller, Josef A1 - Rapp, Michael A. A1 - Rieckmann, Nina T1 - Drug and Exercise Treatment of Alzheimer Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Effects on Cognition in Randomized Controlled Trials JF - The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry N2 - Objective: Demographic changes are increasing the pressure to improve therapeutic strategies against cognitive decline in Alzheimer disease (AD) and mild cognitive impairment (MCI). Besides drug treatment, physical activity seems to be a promising intervention target as epidemiological and clinical studies suggest beneficial effects of exercise training on cognition. Using comparable inclusion and exclusion criteria, we analyzed the efficacy of drug therapy (cholinesterase inhibitors, memantine, and Ginkgo biloba) and exercise interventions for improving cognition in AD and MCI populations. Methods: We searched The Cochrane Library, EBSCO, OVID, Web of Science, and U.S Food and Drug Administration data from inception through October 30, 2013. Randomized controlled trials in which at least one treatment arm consisted of an exercise or a pharmacological intervention for AD or MCI patients, and which had either a non-exposed control condition or a control condition that received another intervention. Treatment discontinuation rates and Standardized Mean Change score using Raw score standardization (SMCR) of cognitive performance were calculated. Results: Discontinuation rates varied substantially and ranged between 0% and 49% with a median of 18%. Significantly increased discontinuation rates were found for galantamine and rivastigmine as compared to placebo in AD studies. Drug treatments resulted in a small pooled effect on cognition (SMCR: 0.23, 95% CI: 0.20 to 0.25) in AD studies (N = 45, 18,434 patients) and no effect in any of the MCI studies (N = 5, 3,693 patients; SMCR: 0.03, 95% CI: 0.00 to 0.005). Exercise interventions had a moderate to strong pooled effect size (SMCR: 0.83, 95% CI: 0.59 to 1.07) in AD studies (N = 4, 119 patients), and a small effect size (SMCR: 0.20, 95% CI: 0.11 to 0.28) in MCI (N = 6, 443 patients). Conclusions: Drug treatments have a small but significant impact on cognitive functioning in AD and exercise has the potential to improve cognition in AD and MCI. Head-to-head trials with sufficient statistical power are necessary to directly compare efficacy, safety, and acceptability. Combining these two approaches might further increase the efficacy of each individual intervention. Identifier: PROSPERO (2013:CRD42013003910). KW - Alzheimer dementia KW - mild cognitive impairment KW - drug KW - exercise Y1 - 2015 U6 - https://doi.org/10.1016/j.jagp.2015.07.007 SN - 1064-7481 SN - 1545-7214 VL - 23 IS - 12 SP - 1234 EP - 1249 PB - Elsevier CY - New York ER - TY - JOUR A1 - Bohlken, Jens A1 - Weber, Simon A1 - Rapp, Michael A. A1 - Kostev, Karel T1 - Continuous treatment with antidementia drugs in Germany 2003-2013: a retrospective database analysis JF - International psychogeriatrics N2 - Background: Continuous treatment is an important indicator of medication adherence in dementia. However, long-term studies in larger clinical settings are lacking, and little is known about moderating effects of patient and service characteristics. Methods: Data from 12,910 outpatients with dementia (mean age 79.2 years; SD = 7.6 years) treated between January 2003 and December 2013 in Germany were included. Continuous treatment was analysed using Kaplan-Meier curves and log-rank tests. In addition, multivariate Cox regression models were fitted with continuous treatment as dependent variable and the predictors antidementia agent, age, gender, medical comorbidities, physician specialty, and health insurance status. Results: After one year of follow-up, nearly 60% of patients continued drug treatment. Donezepil (HR: 0.88; 95% CI: 0.82-0.95) and memantine (HR: 0.85; 0.79-0.91) patients were less likely to be discontinued treatment as compared to rivastigmine users. Patients were less likely to be discontinued if they were treated by specialist physicians as compared to general practitioners (HR: 0.44; 0.41-0.48). Younger male patients and patients who had private health insurance had a lower discontinuation risk. Regarding comorbidity, patients were more likely to be continuously treated with the index substance if a diagnosis of heart failure or hypertension had been diagnosed at baseline. Conclusions: Our results imply that besides type of antidementia agent, involvement of a specialist in the complex process of prescribing antidementia drugs can provide meaningful benefits to patients, in terms of more disease-specific and continuous treatment. KW - adherence KW - cholinesterase inhibitors KW - memantine Y1 - 2015 U6 - https://doi.org/10.1017/S1041610215000654 SN - 1041-6102 SN - 1741-203X VL - 27 IS - 8 SP - 1335 EP - 1342 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Heinzel, Stephan A1 - Riemer, Thomas G. A1 - Schulte, Stefanie A1 - Onken, Johanna A1 - Heinz, Andreas A1 - Rapp, Michael A. T1 - Catechol-O-methyltransferase (COMT) genotype affects age-related changes in plasticity in working memory: a pilot study JF - BioMed research international N2 - Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24-30 years) and 25 older (aged 60-75 years) healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P < .001), which was larger in younger as compared to older adults (P < .001). Age-related differences were qualified by an interaction with COMT genotype (P < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism. Y1 - 2014 U6 - https://doi.org/10.1155/2014/414351 SN - 2314-6133 SN - 2314-6141 PB - Hindawi Publishing Corp. CY - New York ER - TY - JOUR A1 - Liu, Shuyan A1 - Schad, Daniel A1 - Kuschpel, Maxim S. A1 - Rapp, Michael A. A1 - Heinz, Andreas T1 - Music and Video Gaming during Breaks BT - Influence on Habitual versus Goal-Directed Decision Making JF - PLoS one N2 - Different systems for habitual versus goal-directed control are thought to underlie human decision-making. Working memory is known to shape these decision-making systems and their interplay, and is known to support goal-directed decision making even under stress. Here, we investigated if and how decision systems are differentially influenced by breaks filled with diverse everyday life activities known to modulate working memory performance. We used a within-subject design where young adults listened to music and played a video game during breaks interleaved with trials of a sequential two-step Markov decision task, designed to assess habitual as well as goal-directed decision making. Based on a neurocomputational model of task performance, we observed that for individuals with a rather limited working memory capacity video gaming as compared to music reduced reliance on the goal-directed decision-making system, while a rather large working memory capacity prevented such a decline. Our findings suggest differential effects of everyday activities on key decision-making processes. KW - Decision making KW - Games KW - Working memory KW - Video games KW - Cognition KW - Cognitive impairment KW - Music cognition KW - Learning Y1 - 2016 U6 - https://doi.org/10.1371/JOURNAL.PONE.0150165 SN - 1932-6203 VL - 11 IS - 3 SP - 1 EP - 12 PB - Public Library of Science CY - Lawrence, Kan. ER -