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Objective: To test the effect of a complex guideline-based intervention on agitation and psychotropic prescriptions.
Design, Setting, Participants: Cluster randomized controlled trial (VIDEANT) with blinded assessment of outcome in 18 nursing homes in Berlin, Germany, comprising 304 dementia patients.
Intervention: Training, support, and activity therapy intervention, delivered at the level of each nursing home, focusing on the management of agitation in dementia. Control group nursing homes received treatment as usual.
Measurements: Levels of agitated and disruptive behavior (Cohen-Mansfield agitation inventory [CMAI]) as the primary outcome. Number of neuroleptics, antidepressants, and cholinesterase inhibitors (ChEIs) prescribed in defined daily dosages (DDDs).
Results: Of 326 patients screened, 304 (93.3%) were eligible and cluster-randomized to 9 intervention (n = 163) and 9 control (n = 141) nursing homes. Data were collected from 287 (94.4%) patients at 10 months. At 10 months, compared with controls, nursing home residents with dementia in the intervention group exhibited significantly less agitation as measured with the CMAI (adjusted mean difference, 6.24; 95% CI 2.03-14.14; P = .009; Cohen's d = 0.43), received fewer neuroleptics (P < .05), more ChEIs (P < .05), and more antidepressants (P < .05).
Conclusion: Complex guideline-based interventions are effective in reducing agitated and disruptive behavior in nursing home residents with dementia. At the same time, increased prescription of ChEIs and antidepressants together with decreased neuroleptic prescription suggests an effect toward guideline-based pharmacotherapy.
Objectives: To investigate the efficacy of animal-assisted therapy (AAT) on symptoms of agitation/aggression and depression in nursing home residents with dementia in a randomized controlled trial. Previous studies have indicated that AAT has beneficial effects on neuropsychiatric symptoms in various psychiatric disorders but few studies have investigated the efficacy of AAT in patients suffering from dementia. Methods: Of 65 nursing home residents with dementia (mean [standard deviation] age: 81.8 [9.2] years; mean Mini-Mental State Examination score: 7.1 [0.7]), 27 matched pairs (N = 54) were randomly assigned to either treatment as usual or treatment as usual combined with AAT, administered over 10 weekly sessions. Blinded raters assessed cognitive impairment with the Mini-Mental State Examination, presence of agitation/aggression with the Cohen-Mansfield Agitation Inventory, and depression with the Dementia Mood Assessment Scale at baseline and during a period of 4 weeks after AAT intervention. Results: In the control group, symptoms of agitation/aggression and depression significantly increased over 10 weeks; in the intervention group, patients receiving combined treatment displayed constant frequency and severity of symptoms of agitation/aggression (F-1,F-48 = 6.43; p <0.05) and depression (F-1,F-48 = 26.54; p <0.001). Symptom amelioration did not occur in either group. Conclusions: AAT is a promising option for the treatment of agitation/aggression and depression in patients with dementia. Our results suggest that AAT may delay progression of neuropsychiatric symptoms in demented nursing home residents. Further research is needed to determine its long-time effects.
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.
Working memory load-dependent brain response predicts behavioral training gains in older adults
(2014)
In the domain of working memory (WM), a sigmoid-shaped relationship between WM load and brain activation patterns has been demonstrated in younger adults. It has been suggested that age-related alterations of this pattern are associated with changes in neural efficiency and capacity. At the same time, WM training studies have shown that some older adults are able to increase their WM performance through training. In this study, functional magnetic resonance imaging during an n-back WM task at different WM load levels was applied to compare blood oxygen level-dependent (BOLD) responses between younger and older participants and to predict gains in WM performance after a subsequent 12-session WM training procedure in older adults. We show that increased neural efficiency and capacity, as reflected by more "youth-like" brain response patterns in regions of interest of the frontoparietal WM network, were associated with better behavioral training outcome beyond the effects of age, sex, education, gray matter volume, and baseline WM performance. Furthermore, at low difficulty levels, decreases in BOLD response were found after WM training. Results indicate that both neural efficiency (i. e., decreased activation at comparable performance levels) and capacity (i. e., increasing activation with increasing WM load) of a WM-related network predict plasticity of the WM system, whereas WM training may specifically increase neural efficiency in older adults.
Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. Methods: Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.
Processing of reward is the basis of adaptive behavior of the human being. Neural correlates of reward processing seem to be influenced by developmental changes from adolescence to late adulthood. The aim of this study is to uncover these neural correlates during a slot machine gambling task across the lifespan. Therefore, we used functional magnetic resonance imaging to investigate 102 volunteers in three different age groups: 34 adolescents, 34 younger adults, and 34 older adults. We focused on the core reward areas ventral striatum (VS) and ventromedial prefrontal cortex (VMPFC), the valence processing associated areas, anterior cingulate cortex (ACC) and insula, as well as information integration associated areas, dorsolateral prefrontal cortex (DLPFC), and inferior parietal lobule (IPL). Results showed that VS and VMPFC were characterized by a hyperactivation in adolescents compared with younger adults. Furthermore, the ACC and insula were characterized by a U-shape pattern (hypoactivation in younger adults compared with adolescents and older adults), whereas the DLPFC and IPL were characterized by a J-shaped form (hyperactivation in older adults compared with younger groups). Furthermore, a functional connectivity analysis revealed an elevated negative functional coupling between the inhibition-related area rIFG and VS in younger adults compared with adolescents. Results indicate that lifespan-related changes during reward anticipation are characterized by different trajectories in different reward network modules and support the hypothesis of an imbalance in maturation of striatal and prefrontal cortex in adolescents. Furthermore, these results suggest compensatory age-specific effects in fronto-parietal regions. Hum Brain Mapp 35:5153-5165, 2014. (c) 2014 Wiley Periodicals, Inc.
Theories of decision-making and its neural substrates have long assumed the existence of two distinct and competing valuation systems, variously described as goal-directed vs. habitual, or, more recently and based on statistical arguments, as model-free vs. model-based reinforcement-learning. Though both have been shown to control choices, the cognitive abilities associated with these systems are under ongoing investigation. Here we examine the link to cognitive abilities, and find that individual differences in processing speed covary with a shift from model-free to model-based choice control in the presence of above-average working memory function. This suggests shared cognitive and neural processes; provides a bridge between literatures on intelligence and valuation; and may guide the development of process models of different valuation components. Furthermore, it provides a rationale for individual differences in the tendency to deploy valuation systems, which may be important for understanding the manifold neuropsychiatric diseases associated with malfunctions of valuation.
Background: Human and animal work suggests a shift from goal-directed to habitual decision-making in addiction. However, the evidence for this in human alcohol dependence is as yet inconclusive. Methods: Twenty-six healthy controls and 26 recently detoxified alcohol-dependent patients underwent behavioral testing with a 2-step task designed to disentangle goal-directed and habitual response patterns. Results: Alcohol-dependent patients showed less evidence of goal-directed choices than healthy controls, particularly after losses. There was no difference in the strength of the habitual component. The group differences did not survive controlling for performance on the Digit Symbol Substitution Task. Conclusion: Chronic alcohol use appears to selectively impair goal-directed function, rather than promoting habitual responding. It appears to do so particularly after nonrewards, and this may be mediated by the effects of alcohol on more general cognitive functions subserved by the prefrontal cortex.
A dimensional approach in psychiatry aims to identify core mechanisms of mental disorders across nosological boundaries.
We compared anticipation of reward between major psychiatric disorders, and investigated whether reward anticipation is impaired in several mental disorders and whether there is a common psychopathological correlate (negative mood) of such an impairment.
During reward anticipation, we observed significant group differences in ventral striatal (VS) activation: patients with schizophrenia, alcohol dependence, and major depression showed significantly less ventral striatal activation compared to healthy controls. Depressive symptoms correlated with dysfunction in reward anticipation regardless of diagnostic entity. There was no significant correlation between anxiety symptoms and VS functional activation.
Our findings demonstrate a neurobiological dysfunction related to reward prediction that transcended disorder categories and was related to measures of depressed mood. The findings underline the potential of a dimensional approach in psychiatry and strengthen the hypothesis that neurobiological research in psychiatric disorders can be targeted at core mechanisms that are likely to be implicated in a range of clinical entities.
Purpose: Ethnic minority groups show elevated suicide attempt rates across Europe. Evidence suggests a similar trend for women of Turkish origin in Germany, yet data on suicidal behaviour in minorities in Germany is scarce. The objective was to examine rates of suicidal behaviour, underlying motives, and to explore the effectiveness of an intervention program.
Methods: From 05/2009-09/2011, data on all suicide attempts among women of Turkish origin who presented at a hospital-based emergency unit in Berlin, Germany, were collected. A multi-modal intervention was conducted in 2010 and the effects of age, generation and the intervention on suicide attempt rates were examined.
Results: At the start, the highest rate was found in women aged 18-24 years with 225.4 (95% CI = 208.8-242.0)/100,000. Adjustment disorder was the most prevalent diagnosis with 49.7% (n = 79), being more common in second-generation women (P = .004). Further analyses suggested an effect of the intervention in the youngest age group (trend change of beta = -1.25; P = .017).
Conclusion: Our findings suggest a particularly high rate of suicide attempts by 18-24-year-old, second-generation women of Turkish origin in Berlin. Furthermore, our results suggest a trend change in suicide attempts in women aged 18-24 years related to a population-based intervention program. (C) 2015 Elsevier Masson SAS. All rights reserved.
Apathy in nursing home residents with dementia: Results from a cluster-randomized controlled trial
(2015)
Purpose: Here we evaluate an interdisciplinary occupational and sport therapy intervention for dementia patients suffering from apathy.
Subjects and methods: A prospective, controlled, rater-blinded, clinical trial with two follow-ups was conducted as part of a larger cluster-randomized trial in 18 nursing homes in Berlin. n = 117 dementia patients with apathy, defined as a score of 40 or more on the apathy evaluation scale (AES) or presence of apathy on the Neuropsychiatric Inventory (NPI), were randomly assigned to intervention or control group. The intervention included 10 months of brief activities, provided once a week. The primary outcome measure was the total score on the AES scale measured directly after the intervention period and again after 12 months.
Results: We found significant group differences with respect to apathy during the 10 month intervention period (F-2,F-82 = 7.79, P < 0.01), which reflected an increase in apathy in the control group, but not in the intervention group. Within one year after the intervention was ceased, the treatment group worsened and no longer differed significantly from the control group (P = 0.55).
Conclusions: Our intervention was effective for the therapy of apathy in dementia, when applied, but not one year after cessation of therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.
Depression is the most prevalent psychiatric disorder in the general population. Despite a large demand for efficient treatment options, the majority of older depressed adults does not receive adequate treatment: Additional low-threshold treatments are needed for this age group. Over the past two decades, a growing number of randomized controlled trials (RCT) have been conducted, testing the efficacy of physical exercise in the alleviation of depression in older adults. This meta-analysis systematically reviews and evaluates these studies; some subanalyses testing specific effects of different types of exercise and settings are also performed. In order to be included, exercise programs of the RCTs had to fulfill the criteria of exercise according to the American College of Sports Medicine, including a sample mean age of 60 or above and an increased level of depressive symptoms. Eighteen trials with 1,063 participants fulfilled our inclusion criteria. A comparison of the posttreatment depression scores between the exercise and control groups revealed a moderate effect size in favor of the exercise groups (standardized mean difference (SMD) of –0.68, p < .001). The effect was comparable to the results achieved when only the eleven trials with low risk of bias were included (SMD = –0.63, p < .001). The subanalyses showed significant effects for all types of exercise and for supervised interventions. The results of this meta-analysis suggest that physical exercise may serve as a feasible, additional intervention to fight depression in older adults. However, because of small sample sizes of the majority of individual trials and high statistical heterogeneity, results must be interpreted carefully.
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).
In 2011, about 1.1-1.4 million patients with dementia were living in Germany, a number expected to rise to three million by 2050. Dementia poses a major challenge to the healthcare system and neuropharmacological service provision. The aim of this study was to determine prescription rates for anti-dementia drugs as well as for neuroleptics, sedative-hypnotics and antidepressants in dementia using the complete nationwide outpatient claims data pertaining to the services of statutory health insurance. We controlled for gender, age, dementia diagnosis, physician specialty (general practitioner GP versus neuropsychiatry specialist physician NPSP), and rural and urban living area. In about one million prevalent dementia patients (N=1,014,710) in 2011, the prescription prevalence rate of anti-dementia drugs was 24.6%; it varied with gender, age, and diagnosis (highest in Alzheimer's disease; 42%), and was higher in patients treated by NPSPs (48% vs. 25% in GPs). At the same time, we found an alarmingly high rate of treatment with neuroleptics in dementia patients (35%), with an only slightly decreased risk in patients treated exclusively by NPSPs (OR=0.86). We found marginal differences between rural and urban areas. Our results show that the majority of anti-dementia drug prescriptions appear guideline-oriented, yet prescription rates are overall comparatively low. On the other hand, neuroleptic drugs, which are associated with excess morbidity and mortality in dementia, were prescribed very frequently, suggesting excess use given current guidelines. We therefore suggest that guideline implementation measures and increasing quality control procedures are needed with respect to the pharmacotherapy of this vulnerable population. (C) 2015 Elsevier B.V. and ECNR All rights reserved.
Continuous treatment with antidementia drugs in Germany 2003-2013: a retrospective database analysis
(2015)
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.
Fluid intelligence (fluid IQ), defined as the capacity for rapid problem solving and behavioral adaptation, is known to be modulated by learning and experience. Both stressful life events (SLES) and neural correlates of learning [specifically, a key mediator of adaptive learning in the brain, namely the ventral striatal representation of prediction errors (PE)] have been shown to be associated with individual differences in fluid IQ. Here, we examine the interaction between adaptive learning signals (using a well-characterized probabilistic reversal learning task in combination with fMRI) and SLES on fluid IQ measures. We find that the correlation between ventral striatal BOLD PE and fluid IQ, which we have previously reported, is quantitatively modulated by the amount of reported SLES. Thus, after experiencing adversity, basic neuronal learning signatures appear to align more closely with a general measure of flexible learning (fluid IQ), a finding complementing studies on the effects of acute stress on learning. The results suggest that an understanding of the neurobiological correlates of trait variables like fluid IQ needs to take socioemotional influences such as chronic stress into account.
The interruption of learning processes by breaks filled with diverse activities is common in everyday life. This study investigated the effects of active computer gaming and passive relaxation (rest and music) breaks on auditory versus visual memory performance. Young adults were exposed to breaks involving (a) open eyes resting, (b) listening to music, and (c) playing a video game, immediately after memorizing auditory versus visual stimuli. To assess learning performance, words were recalled directly after the break (an 8:30 minute delay) and were recalled and recognized again after 7 days. Based on linear mixed-effects modeling, it was found that playing the Angry Birds video game during a short learning break impaired long-term retrieval in auditory learning but enhanced long-term retrieval in visual learning compared with the music and rest conditions. These differential effects of video games on visual versus auditory learning suggest specific interference of common break activities on learning.
The interruption of learning processes by breaks filled with diverse activities is common in everyday life. We investigated the effects of active computer gaming and passive relaxation (rest and music) breaks on working memory performance. Young adults were exposed to breaks involving (i) eyes-open resting, (ii) listening to music and (iii) playing the video game “Angry Birds” before performing the n-back working memory task. Based on linear mixed-effects modeling, we found that playing the “Angry Birds” video game during a short learning break led to a decline in task performance over the course of the task as compared to eyes-open resting and listening to music, although overall task performance was not impaired. This effect was associated with high levels of daily mind wandering and low self-reported ability to concentrate. These findings indicate that video games can negatively affect working memory performance over time when played in between learning tasks. We suggest further investigation of these effects because of their relevance to everyday activity.
Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N=27). All participants also underwent 6-[F-18]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation by RPEs nor striatal dopamine synthesis capacity differed between groups. However, ventral striatal coding of RPEs correlated inversely with craving in patients. Furthermore, we found a negative correlation between ventral striatal coding of RPEs and dopamine synthesis capacity in healthy controls, but not in alcohol-dependent patients. Moderator analyses showed that the magnitude of the association between dopamine synthesis capacity and RPE coding depended on the amount of chronic, habitual alcohol intake. Despite the relatively small sample size, a power analysis supports the reported results. Using a multimodal imaging approach, this study suggests that dopaminergic modulation of neural learning signals is disrupted in alcohol dependence in proportion to long-term alcohol intake of patients. Alcohol intake may perpetuate itself by interfering with dopaminergic modulation of neural learning signals in the ventral striatum, thus increasing craving for habitual drug intake.