Chronic pain in osteoarthritis of the hip is associated with selective cognitive impairment.

INTRODUCTION: Chronic pain of various origin is known to be associated with selective cognitive impairment. Osteoarthritis (OA) of the hip is one of the leading causes of chronic pain in the adult population, but its association with cognitive performance has not been evaluated. Here, we investigate the effect of chronic pain due to unilateral OA of one hip and no further source of chronic pain on cognitive performance. MATERIALS AND METHODS: A neuropsychological test battery, consisting of the Mini-Mental State Examination, Rey-Osterrieth complex figure test, Rivermead behavioural memory test, d2 test of attention, and F-A-S test was applied in 148 patients and 82 healthy pain-free control individuals. The influence of potentially confounding factors such as depression and anxiety was examined. RESULTS: Patients with OA of the hip showed decreased performance in specific neuropsychological tests. Performance in verbal and visual short-term and long-term memory and selective attention tests was significantly poorer compared to healthy controls. Whereas the executive functions "updating", "set shifting", "response inhibition" and "reflection" appear intact, "problem solving" and "planning" were impaired. None of the confounders showed any influence on cognitive performance in both study groups. CONCLUSION: We conclude that chronic pain secondary to end-stage hip OA is associated with selective cognitive impairment. Future studies are required to investigate the effect of total hip arthroplasty on cognitive performance.

Efficacy of metacognitive training for depression as add-on intervention for patients with depression in acute intensive psychiatric inpatient care: A randomized controlled trial.

BACKGROUND: Metacognitive training for depression (D-MCT) is a novel low-intensity group training for economic treatment of depression. Previous studies demonstrate its efficacy in moderately depressed outpatients. The present study evaluated efficacy and patients' perspective of the D-MCT in severely depressed psychiatric inpatients. METHODS: In a randomized-controlled trial, 75 individuals with a major depressive disorder (MDD) were allocated to D-MCT versus euthymic therapy as add-on (twice a week) to cognitive-behavioural-based (CBT) inpatient-care. Depressive symptoms (HDRS, BDI), dysfunctional (meta)cognition (DAS, MCQ-30) and subjective appraisal were assessed at baseline, 4 weeks (post) and 3 months (follow-up). RESULTS: Participants in both conditions showed a large decline in depression at post and follow-up-assessment. No superior add-effect of D-MCT versus active control emerged for depression severity on top of the inpatient care. However, among patients with a diagnosis of MDD with no (vs. at least one) comorbidity, D-MCT participants showed a larger decline in depressive (meta-)cognition at follow-up with medium-to-large effect sizes. D-MCT was evaluated as superior in overall appraisal, treatment preference, motivation and satisfaction. LIMITATIONS: The follow-up time interval of 3 months may have been too short to detect long-term effects. There is emerging evidence that modification of (meta)cognition unfolds its full effects only with time. Effects of CBT inpatient-care on outcome parameters cannot be differentiated. CONCLUSIONS: Although D-MCT as an add-on was not superior in complete case analyses, results suggest greater benefit for patients with MDD and no comorbidity. D-MCT proved feasible in acute-psychiatric inpatient-care and was highly accepted by patients. Future studies should investigate the role of modified (meta)cognition on long-term treatment outcome, including dropout and relapse rates.

Effect of intravenous alteplase on post-stroke depression in the WAKE UP trial.

BACKGROUND AND PURPOSE: The aim was to study the effect of intravenous alteplase on the development of post-stroke depression (PSD) in acute stroke patients, and to identify predictors of PSD. METHODS: This post hoc analysis included patients with unknown onset stroke randomized to treatment with alteplase or placebo in the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290), in whom a composite end-point of PSD was defined as a Beck Depression Inventory ≥10, medication with an antidepressant, or depression recorded as an adverse event. Multiple logistic regression was used to identify predictors of PSD at 90 days. Structural equation modelling was applied to assess the indirect effect of thrombolysis on PSD mediated by the modified Rankin Scale. RESULTS: Information on the composite end-point was available for 438 of 503 randomized patients. PSD was present in 96 of 224 (42.9%) patients in the alteplase group and 115 of 214 (53.7%) in the placebo group (odds ratio 0.63; 95% confidence interval 0.43-0.94; p = 0.022; adjusted for age and National Institutes of Health Stroke Scale at baseline). Prognostic factors associated with PSD included baseline medication with antidepressants, higher lesion volume, history of depression and assignment to placebo. While 65% of the effect of thrombolysis on PSD were caused directly, 35% were mediated by an improvement of the mRS. CONCLUSIONS: Treatment with alteplase in patients with acute stroke resulted in lower rates of depression at 90 days, which were only partially explained by reduced functional disability. Predictors of PSD including history and clinical characteristics may help in identifying patients at risk of PSD.

Metacognitive Training for Depression: Feasibility, safety and acceptability of two new treatment modules to reduce suicidality.

Recent evidence favours psychological interventions explicitly targeting suicidality; however, group treatments on suicidality are rare and are assumed to have unfavourable effects. We developed two modules specifically addressing suicidality that replace two existing modules in the Metacognitive Training for Depression (D-MCT). The aim of the current study was to examine the feasibility, safety, and acceptability of this intervention (D-MCT/S). Forty-eight inpatients with depression received eight sessions of D-MCT/S over 4 weeks in addition to standard treatment. Patients were assessed before the training, 4 and 8 weeks later regarding suicidality (primary outcome: Beck Suicide Scale [BSS]), hopelessness, depression (e.g. Hamilton Depression Rating Scale [HDRS]), dysfunctional attitudes, and self-esteem. Negative effects of the modules and subjective appraisal were assessed. Suicidality, hopelessness, and depression decreased over time. Whereas the effects on the BSS only reached trend level, a large effect was observed when the suicide item of the HDRS was used. Two of the 46 patients (4%) reported a deterioration in their symptoms, but this was not associated with the D-MCT/S. Negative effects of the general training were rather low, and acceptability was high. In general, patients evaluated the two new modules on suicidality similarly to the established modules. However, both modules were assessed as distressing by 39% of the patients. When we addressed suicidality in the D-MCT/S, we did not observe any contagious effects. In fact, the pilot versions of the two modules on suicidality are promising in terms of feasibility, safety, and acceptability. The results will be used to improve current shortcomings. The trial was registered with the German Clinical Trials Register (#DRKS-ID: DRKS00010543) on 23 August 2016.

Brief Web-Based Intervention for Depression: Randomized Controlled Trial on Behavioral Activation.

BACKGROUND: Web-based interventions have been shown to be effective for the treatment of depression. However, interventions are often complex and include a variety of elements, making it difficult to identify the most effective component(s). OBJECTIVE: The aim of this pilot study was to shed light on mechanisms in the online treatment of depression by comparing a single-module, fully automated intervention for depression (internet-based behavioral activation [iBA]) to a nonoverlapping active control intervention and a nonactive control group. METHODS: We assessed 104 people with at least mild depressive symptoms (Patient Health Questionnaire-9, >4) via the internet at baseline (t0) and 2 weeks (t1) and 4 weeks (t2) later. After the t0 assessment, participants were randomly allocated to one of three groups: (1) iBA (n=37), (2) active control using a brief internet-based mindfulness intervention (iMBI, n=32), or (3) care as usual (CAU, n=35). The primary outcome was improvement in depressive symptoms, as measured using the Patient Health Questionnaire-9. Secondary parameters included changes in activity, dysfunctional attitudes, and quality of life. RESULTS: While groups did not differ regarding the change in depression from t0 to t1 (ηp2=.007, P=.746) or t0 to t2 (ηp2=.008, P=.735), iBA was associated with a larger decrease in dysfunctional attitudes from t0 to t2 in comparison to CAU (ηp2=.053, P=.04) and a larger increase in activity from t0 to t1 than the pooled control groups (ηp2=.060, P=.02). A change in depression from t0 to t2 was mediated by a change in activity from t0 to t1. At t1, 22% (6/27) of the participants in the iBA group and 12% (3/25) of the participants in the iMBI group indicated that they did not use the intervention. CONCLUSIONS: Although we did not find support for the short-term efficacy of the single-module iBA regarding depression, long-term effects are still conceivable, potentially initiated by changes in secondary outcomes. Future studies should use a longer intervention and follow-up interval. TRIAL REGISTRATION: DKRS (#DRKS00011562).

Preoperative Depression and Plasma Cortisol Levels as Predictors of Delirium after Cardiac Surgery.

BACKGROUND: Delirium is common in old patients who undergo cardiac surgery, and it is associated with adverse outcomes. The genesis of delirium is thought to be multi-factorial, but it is still not well understood. Symptoms of depression and elevated cortisol level have been described in some previous studies as factors associated with delirium, suggesting a shared pathophysiology. AIMS: The objective of the present study was to determine whether preoperative depression symptoms and increased cortisol level represent risk factors for delirium after cardiac surgery. METHODS: We performed a prospective cohort study in 183 patients aged >50 years undergoing elective cardiac surgery. The Geriatric Depression Scale (GDS) was used to assess patients for depressive symptoms before surgery. Preoperative plasma cortisol levels were available in 145 participants. Delirium was diagnosed using the Confusion Assessment Method for Intensive Care Unit (CAM-ICU) during the first 7 days after surgery. Spearman correlation was used for correlations between GDS, Mini-Mental State Examination (MMSE), Charlson comorbidity index, and age. Binary logistic regression was used to determine whether GDS and cortisol levels predict postoperative delirium. RESULTS: Delirium occurred in 60 patients out of 183 (32.8%) included and lasted 2.3 days (SD 1.36). GDS was correlated with age (p = 0.001) and comorbidity index (p = 0.003) and inversely correlated with MMSE score (p < 0.001). Higher preoperative GDS scores were associated with incidence of delirium in the postoperative period (p = 0.002). The association was significant after controlling for age, MMSE score, history of stroke, and Charlson comorbidity index (p = 0.045). Preoperative cortisol level was not associated with the development of postoperative delirium. CONCLUSION: Our results suggest that a higher preoperative depression score is associated with an increased risk of postoperative delirium. On the other hand, preoperative plasma cortisol level does not seem to be a predictor of delirium after surgery. Further studies are needed to determine the potential of preoperative depression treatment to prevent postoperative delirium.

Association between fully automated MRI-based volumetry of different brain regions and neuropsychological test performance in patients with amnestic mild cognitive impairment and Alzheimer's disease.

Fully automated magnetic resonance imaging (MRI)-based volumetry may serve as biomarker for the diagnosis in patients with mild cognitive impairment (MCI) or dementia. We aimed at investigating the relation between fully automated MRI-based volumetric measures and neuropsychological test performance in amnestic MCI and patients with mild dementia due to Alzheimer's disease (AD) in a cross-sectional and longitudinal study. In order to assess a possible prognostic value of fully automated MRI-based volumetry for future cognitive performance, the rate of change of neuropsychological test performance over time was also tested for its correlation with fully automated MRI-based volumetry at baseline. In 50 subjects, 18 with amnestic MCI, 21 with mild AD, and 11 controls, neuropsychological testing and T1-weighted MRI were performed at baseline and at a mean follow-up interval of 2.1 ± 0.5 years (n = 19). Fully automated MRI volumetry of the grey matter volume (GMV) was performed using a combined stereotactic normalisation and segmentation approach as provided by SPM8 and a set of pre-defined binary lobe masks. Left and right hippocampus masks were derived from probabilistic cytoarchitectonic maps. Volumes of the inner and outer liquor space were also determined automatically from the MRI. Pearson's test was used for the correlation analyses. Left hippocampal GMV was significantly correlated with performance in memory tasks, and left temporal GMV was related to performance in language tasks. Bilateral frontal, parietal and occipital GMVs were correlated to performance in neuropsychological tests comprising multiple domains. Rate of GMV change in the left hippocampus was correlated with decline of performance in the Boston Naming Test (BNT), Mini-Mental Status Examination, and trail making test B (TMT-B). The decrease of BNT and TMT-A performance over time correlated with the loss of grey matter in multiple brain regions. We conclude that fully automated MRI-based volumetry allows detection of regional grey matter volume loss that correlates with neuropsychological performance in patients with amnestic MCI or mild AD. Because of the high level of automation, MRI-based volumetry may easily be integrated into clinical routine to complement the current diagnostic procedure.

Session-Specific Effects on Suicidality in Group Therapy: No Evidence for Contagion.

OBJECTIVE: Explicitly addressing suicidality in group therapy is often avoided due to the fear of contagion effects. However, there is some evidence that this fear is not valid. Therefore, the present study aims at contributing to this question by investigating the session-specific effects of two modules on suicidality that are part of the Metacognitive Training for Depression (D-MCT/S). METHODS: Forty-four patients with depression participated in the two modules on suicidality of the D-MCT/S. Before and after each group session, patients filled out a questionnaire asking for symptoms of suicidality, associated cognitions (e.g., hopelessness), and associated emotions (e.g., anger). Data were analyzed by linear mixed-effect models. RESULTS: Approximately 84% of the patients had experienced lifetime suicidal ideation. No within- or between-session effects were found for the modules on suicidality. Sample size was large enough to find small to medium effects (within-session analyses) and medium to large effects (between-session analyses). CONCLUSION: The modules on suicidality did not specifically change suicidal symptoms or associated cognitions and emotions immediately or by the next session. Most importantly, our results disconfirm evidence on deterioration when suicidality is addressed in a highly structured group setting. Whether the current findings also apply to other forms of group therapies needs to be investigated in future studies. HIGHLIGHTSSession-specific investigations allow a thoroughly examination of an interventionMetacognitive Training for Depression showed no contagion effect on suicidality.

Effect of one-year vitamin C- and E-supplementation on cerebrospinal fluid oxidation parameters and clinical course in Alzheimer's disease.

Antioxidant vitamins are being widely discussed as a therapeutic option in Alzheimer's disease (AD). We recently found that supplementation with vitamin C and E over 1 month leads to an increase of their levels in cerebrospinal fluid (CSF) and a reduction of CSF lipid peroxidation. In the present study, we followed-up the biochemical and clinical effect of vitamin C and E supplementation in an open clinical trial over 1 year. Twelve AD patients stably taking a cholinesterase inhibitor were supplemented with vitamin C (1,000 mg/day) and E (400 I.U./day), while 11 patients taking cholinergic medication only served as a control group. Cognition was assessed at baseline, after 6 months and 12 months using the Mini-Mental State Examination; a more detailed testing of cognitive function was performed at baseline and after 12 months. From eight of the vitamin-supplemented patients, CSF was taken at baseline, after 1 month and after 1 year to measure the antioxidant effect of vitamin supplementation on CSF lipids using a recently established in vitro oxidation assay. CSF antioxidant vitamins were significantly increased after 1 month and 1 year of supplementation, while in vitro oxidation of CSF lipids was significantly reduced only after 1 year of the supplementation. The clinical course of AD did not significantly differ between the vitamin and the control group. We conclude that supplementation with vitamins E and C did not have a significant effect on the course of AD over 1 year despite of a limited antioxidant effect that could be observed in CSF.

Mid-term improvement of cognitive performance after total hip arthroplasty in patients with osteoarthritis of the hip : a prospective cohort study.

AIMS: The aim of this study was to determine whether total hip arthroplasty (THA) for chronic hip pain due to unilateral primary osteoarthritis (OA) has a beneficial effect on cognitive performance. METHODS: A prospective cohort study was conducted with 101 patients with end-stage hip OA scheduled for THA (mean age 67.4 years (SD 9.5), 51.5% female (n = 52)). Patients were assessed at baseline as well as after three and months. Primary outcome was cognitive performance measured by d2 Test of Attention at six months, Trail Making Test (TMT), FAS-test, Rivermead Behavioural Memory Test (RBMT; story recall subtest), and Rey-Osterrieth Complex Figure Test (ROCF). The improvement of cognitive performance was analyzed using repeated measures analysis of variance. RESULTS: At six months, there was significant improvement in attention, working speed and concentration (d2-test; p < 0.001), visual construction and visual memory (ROCF; p < 0.001), semantic memory (FAS-test; p = 0.009), verbal episodic memory (RBMT; immediate recall p = 0.023, delayed recall p = 0.026), as well as pain (p < 0.001) with small to large effect sizes. Attention, concentration, and visual as well as verbal episodic memory improved significantly with medium effect sizes over η2 partial = 0.06. In these cognitive domains the within-group difference exceeded the minimum clinically important difference. CONCLUSION: THA is associated with clinically relevant postoperative improvement in the cognitive functions of attention, concentration, and memory. These data support the concept of a broad interaction of arthroplasty with central nervous system function. Cite this article: Bone Joint J 2022;104-B(3):331-340.

Do implicit measures improve suicide risk prediction? An 18-month prospective study using different tasks.

BACKGROUND: There is accumulating evidence that implicit measures improve the prediction of suicidality within a 6-month follow-up period in psychiatric populations. Building upon these results, we set out to expand the follow-up period and to investigate various implicit methods. METHODS: Seventy-nine inpatients completed the Beck Scale for Suicidal Ideation (BSS) and a range of implicit measures: three implicit association tests (IATs: Death; Self-harm-Me/Others; Self-Harm-Good/Bad) and a subliminal priming task (with separate scores for negative and positive adjectives, each indicating the association between the primes "dying" and "growing"). After 18 months, we reached n = 52 patients and reassessed suicidal ideation, plans, and attempts. RESULTS: In a hierarchical regression, the five implicit task indices were entered after the patient's age, gender, and BSS score at baseline. The implicit scores improved prediction of BSS scores after 18 months compared to prediction based on age, gender, and BSS score at baseline alone. However, none of the implicit measures was associated with suicide plans or attempts during the follow-up period. CONCLUSION: Results suggest that implicit measures can be a useful assessment tool for the prediction of suicidal ideation, even beyond the BSS. However, long-term prediction of suicide plans or attempts using implicit measures seems limited.

B-spline-based stereotactical normalization of brain FDG PET scans in suspected neurodegenerative disease: impact on voxel-based statistical single-subject analysis.

A b-spline-based method 'Lobster', originally designed as a general technique for non-linear image registration, was tailored for stereotactical normalization of brain FDG PET scans. Lobster was compared with the normalization methods of SPM2 and Neurostat with respect to the impact on the accuracy of voxel-based statistical analysis. (i) Computer simulation: Seven representative patterns of cortical hypometabolism served as artificial ground truth. They were inserted into 26 normal control scans with different simulated severity levels. After stereotactical normalization and voxel-based testing, statistical maps were compared voxel-by-voxel with the ground truth. This was done at different levels of statistical significance. There was a highly significant effect of the stereotactical normalization method on the area under the resulting ROC curve. Lobster showed the best average performance and was most stable with respect to variation of the severity level. (ii) Clinical evaluation: Statistical maps were obtained for the normal controls as well as patients with Alzheimer's disease (AD, n=44), Lewy-Body disease (LBD, 9), fronto-temporal dementia (FTD, 13), and cortico-basal dementia (CBD, 4). These maps were classified as normal, AD, LBD, FTD, or CBD by two experienced readers. The stereotactical normalization method had no significant effect on classification by of each of the experts, but it appeared to affect agreement between the experts. In conclusion, Lobster is appropriate for use in single-subject analysis of brain FDG PET scans in suspected dementia, both in early diagnosis (mild hypometabolism) and in differential diagnosis in advanced disease stages (moderate to severe hypometabolism). The computer simulation framework developed in the present study appears appropriate for quantitative evaluation of the impact of the different processing steps and their interaction on the performance of voxel-based single-subject analysis.

Multicentre variability of MRI-based medial temporal lobe volumetry in Alzheimer's disease.

Magnetic resonance imaging (MRI)-based volumetry of medial temporal lobe regions is among the best established biomarker candidates of Alzheimer's disease (AD) to date. This study assessed the effect of multicentre variability of MRI-based hippocampus and amygdala volumetry on the discrimination between patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and on the association of morphological changes with ApoE4 genotype and cognition. We studied 113 patients with clinically probable AD and 150 patients with amnestic MCI using high-resolution MRI scans obtained at 12 clinical sites. We determined effect sizes of group discrimination and random effects linear models, considering multicentre variability. Hippocampus and amygdala volumes were significantly reduced in AD compared with MCI patients using data pooled across centres. Multicentre variability did not significantly affect the power to detect a volume difference between AD and MCI patients. Among cognitive measures, delayed recall of verbal and non-verbal material was significantly correlated with hippocampus and amygdala volumes. Amygdala and hippocampus volumes were not associated with ApoE4 genotype in AD or MCI. Our data indicate that multicentre acquisition of MRI data using manual volumetry is reliable and feasible for cross-sectional diagnostic studies, and they replicate essential findings from smaller scale monocentre studies.

Association between FDG uptake, CSF biomarkers and cognitive performance in patients with probable Alzheimer's disease.

PURPOSE: Brain imaging of FDG uptake and cerebrospinal fluid (CSF) concentration of amyloid-beta 1-42 (Abeta(1-42)) or tau proteins are promising biomarkers in the diagnosis of Alzheimer's disease (AD). There is still uncertainty regarding any association between decreased FDG uptake and alterations in CSF markers. METHODS: The relationship between FDG uptake, CSF Abeta(1-42) and total tau (T-tau), as well as the Mini-Mental State Examination (MMSE) score was investigated in 34 subjects with probable AD using step-wise linear regression. FDG uptake was scaled to the pons. RESULTS: Scaled FDG uptake was significantly reduced in the probable AD subjects compared to 17 controls bilaterally in the precuneus/posterior cingulate area, angular gyrus/inferior parietal cortex, inferior temporal/midtemporal cortex, midfrontal cortex, and left caudate. Voxel-based single-subject analysis of the probable AD subjects at p < 0.001 (uncorrected) revealed a total volume of significant hypometabolism ranging from 0 to 452 ml (median 70 ml). The total hypometabolic volume was negatively correlated with the MMSE score, but it was not correlated with the CSF measures. VOI-based step-wise linear regression revealed that scaled FDG uptake in the precuneus/posterior cingulate was negatively correlated with CSF Abeta(1-42). Scaled FDG uptake in the caudate was positively correlated with CSF T-tau. CONCLUSION: The extent and local severity of the reduction in FDG uptake in probable AD subjects are associated with cognitive impairment. In addition, there appears to be a relationship between local FDG uptake and CSF biomarkers which differs between different brain regions.

Asymmetrical dimethylarginine is increased in plasma and decreased in cerebrospinal fluid of patients with Alzheimer's disease.

BACKGROUND: Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase and may alter NO production during pathological conditions. Concerning Alzheimer's disease (AD), there are reports on altered cerebral NO metabolism, but only few studies on ADMA concentrations in plasma and cerebrospinal fluid (CSF). METHODS: We assessed plasma ADMA in 80 AD patients and 80 age- and gender-matched controls and CSF ADMA in a subgroup of 53 AD patients and 20 controls. RESULTS: ADMA plasma concentrations were increased, while CSF ADMA concentrations were decreased in AD patients. There was a significant association between decreasing CSF ADMA levels and the severity of cognitive impairment. CONCLUSION: Elevated ADMA in plasma might be a contributing factor for AD through alterations of NO metabolism, for example decreased cerebral microperfusion, while decreased levels of CSF ADMA might lead to a cerebral increase of NO, peroxynitrite production and oxidative protein damage. Our study reveals different mechanisms of plasma and CSF ADMA regulation, both potentially contributing to AD pathology.

Adherence to medication in patients with dementia: predictors and strategies for improvement.

Measures to facilitate patient medication adherence should be considered an integral part of the comprehensive care of older patients with multiple diseases. However, impairment of cognitive functions and dementia, in particular, may substantially compromise adherence behaviour. Therefore, a literature review was performed to identify factors associated with adherence to medication in patients with cognitive impairment or dementia, and to discuss strategies for improvement of non-adherence. Evidence-based information on how to deal with adherence to medication in patients with dementia is scarce because of a lack of specific studies. However, there is increasing knowledge about factors influencing medication adherence behaviour in older age, and emerging insight into the relationships between adherence behaviour and cognitive capacity, memory and executive function, in particular. Nevertheless, understanding elderly persons' strategies for maintaining regular use of even complex drug regimens is still limited. Progress of research in this field is needed. It is notable that measures to improve adherence consist of combinations of educational interventions and cognitive support but assessment of study participants' cognitive function is rare. In clinical practice, awareness of non-adherence as a result of cognitive impairment is relatively low. The most important step is early detection of cognitive impairment when this is impacting negatively on medication management. A practical geriatric screening test is recommended to identify memory problems and further functional impairments associated with cognitive impairment. Performance-based assessments might be useful for screening medication management capacity, in addition to a careful drug history, inspection of all medicines used (including over-the-counter drugs) and proxy information. However, no feasible screening methods have as yet found their way into clinical practice. Patients with impaired executive function, lack of awareness of illness and personality traits such as independency and high self-confidence may be at particular risk of non-adherence. The question is when to switch patient medication self-management to another person's responsibility if cognitive decline progresses. Further research is needed on measures to differentiate cognitive function and the relationships between memory concerns, memory strategy use and medication management. Also, studies evaluating the influence of personal support, health status and depression on the memory strategies used are needed. It is important to assess patients' attitudes toward medication and their relationship with proxies. Strategies for facilitating medication adherence in patients with dementia include prescribing as few medicines as possible, tailoring dose regimens to personal habits, and coordinating all drug dosing schedules as much as possible. When providing medication organizers, it is important to observe the patient's ability to use devices appropriately. In addition, automated computer-based reminding aids, online medication monitoring and telemonitoring may be helpful for patients with mild dementia. The decision as to when assistance with medication self-management is needed has to be made taking into account patient independency and safety aspects. This holds true for medicines with a narrow therapeutic range, in particular. Interactions among the individual patient's cognitive status, mood, level of self-efficacy and particular living situation must also be taken into consideration when searching for the optimal medication adherence strategy. No evidence-based recommendations can be given as yet. However, comprehensive assessment of the individual patient and careful consideration of all potential drug-related problems will probably help facilitate adherence and prevent compromised health outcomes in patients with dementia.

Metacognitive Training for Depression (D-MCT) reduces false memories in depression. A randomized controlled trial.

Metacognitive Training for Depression (D-MCT) is a highly standardized group program targeted at depression-related ("Beckian") emotional as well as cognitive biases, including mood-congruent and false memory. While prior results are promising with respect to psychopathological outcomes (depression), it is unclear whether D-MCT also meets its goal of improving cognitive biases, such as false memories. In the framework of a randomized controlled trial (registered trial, DRKS00007907), we investigated whether D-MCT is superior to an active control condition (health training, HT) in reducing the susceptibility of depressed patients for false memories. False memories were examined using parallel versions of a visual variant of the Deese-Roediger McDermott paradigm. Both groups committed less false memories at post assessment after 4 weeks compared to baseline. Relative to HT, D-MCT led to a significant decrease in high-confident false memories over time. The study presents first evidence that D-MCT decreases the susceptibility of depressed patients for false memories, particularly for errors made with high confidence that are presumably the most "toxic" in terms of mood-congruent memory distortions.

Are we exaggerating neuropsychological impairment in depression? Reopening a closed chapter.

BACKGROUND: Meta-analyses conclude that individuals with depression display neurocognitive deficits. However, the extent to which some of these impairments occur due to secondary influences, and thus in part represent epiphenomena, has rarely been tested. Therefore, the authors examined the impact of performance motivation, attitude towards cognitive assessment, and momentary symptoms during assessment on neuropsychological test results in depression. RESEARCH DESIGN AND METHODS: Forty-five patients with depression and 60 nonclinical individuals underwent a comprehensive neuropsychological test battery. Before and after the assessment, each participant was asked to complete the Momentary Influences, Attitudes and Motivation Impact on Cognitive Performance Scale (MIAMI). RESULTS: As hypothesized, patients with depression performed worse than nonclinical controls on most neuropsychological parameters. Group differences achieved a medium effect size for parameters tapping speed and a large effect for parameters tapping accuracy. Yet, only one fourth of the patient population displayed abnormal scores (≥ 1 SD below the population mean). In line with the hypothesis, patients with depression were more fearful of test outcomes, complained more about negative momentary influences, and were less motivated (based on retrospective assessment) than controls, as assessed with the MIAMI. The MIAMI total score mediated the relationship between group status and test scores in three out of four analyses. When MIAMI scores were entered as covariate, group differences were largely reduced. DISCUSSION: Patients with depression show a more negative attitude towards testing, lower performance motivation, and more negative momentary influences, all of which induce malperformance. The results suggest that performance dysfunction does not necessarily mirror brain dysfunction in areas hosting cognitive functions but is confounded with other factors. Greater caution is warranted when interpreting the results of neuropsychological tests in depressed patients.

Pharmacological treatment of non-Alzheimer dementias.

PURPOSE OF REVIEW: One hundred years after the first description by Alois Alzheimer and with the advent of first pharmacological treatments, most researchers concentrate on Alzheimer's disease. Millions of patients, however, suffer from other dementias and search for help beyond diagnosis. RECENT FINDINGS: New clinical data concerning the treatment of non-Alzheimer dementias mainly relate to the clinical use of antidementiva that is already approved for the treatment of Alzheimer's disease. Few studies test new pharmacological paradigmata. For some forms like vascular dementias, the possibility of prevention is the most valuable approach that should be enforced more aggressively. For other savaging dementias new unconventional treatment trials should be encouraged. SUMMARY: Research for non-Alzheimer dementias lags behind those for the Alzheimer field. For many patients, we still have nothing but words. At the same time, probably with regard to cost constraints, some acteurs like health insurances and legislators are inclined to nurture therapeutic nihilism and cultivate ethical qualms and demurs instead of supporting clinical trials or at least not blocking them with bureaucratic hand-cuffs, whereas pharmaceutical companies contemplate naturally over questions like return of investment. The clinical researchers should fight this fatigue and look for ways out of this quagmire for our patients.

Effects of online intervention for depression on mood and positive symptoms in schizophrenia.

BACKGROUND: Depression is common in schizophrenia. Whereas the improvement of mood and self-esteem represents a subjective treatment priority for many patients, depression is rarely a primary target for clinical intervention. The present trial examined whether an online intervention for depression can ameliorate depressive symptoms in schizophrenia. METHODS: A total of 58 individuals with schizophrenia were invited to participate in an online survey which encompassed the Center for Epidemiologic Studies-Depression Scale (CES-D, primary outcome), the Patient-Health-Questionnaire-9 (PHQ-9) and the Paranoia Checklist. Subsequently, telephone interviews were conducted to verify diagnostic status and assess symptoms (Positive and Negative Syndrome Scale, PANSS). Participants were randomized either to the experimental condition (online depression intervention) or to a waitlist control condition. Three months after inclusion, a reassessment was carried out (self-report and telephone interview blind for group condition). The trial was registered (registration: DRKS00007888). RESULTS: Participants in the treatment group showed a significant decline of depressive symptoms at a medium-to-large effect size, as assessed with the CES-D and the PANSS depression item, in comparison to the waitlist control group (completer (CC) and intention-to-treat analyses (ITT)). For the PHQ-9 (CC and ITT) and the PANSS distress subscale (CC only) significance was bordered at a medium effect size. Completion at the post-assessment after three months was 84%. DISCUSSION: Depression in schizophrenia is both underdiagnosed and undertreated. To reduce the large treatment gap in the disorder, low threshold strategies are urgently needed. Online treatment and bibliotherapy may represent valuable tools to address patients' needs beyond the treatment of the core positive syndrome.