Reduced awareness of cognitive deficits in idiopathic normal pressure hydrocephalus and its change following lumbar puncture.

OBJECTIVE: Awareness of cognitive deficits is related to executive functions and may, therefore, be sensitive to the effects of lumbar puncture (LP) in idiopathic normal pressure hydrocephalus (iNPH). Although a reduction in awareness of cognitive deficits (RACD) has been previously described in iNPH, there is a lack of systematic, psychometrically validated reports. In this study, we investigated RACD and its LP-related changes in iNPH patients and compared them with those in clinical and healthy control groups. METHODS: RACD was assessed before and after lumbar puncture (LP) in 24 patients (14 iNPH, 10 other age-associated cognitive syndromes; AACS) and compared with 23 healthy controls (HC), employing two RACD measures alongside cognitive examination. Local metacognition was measured using a visual percentile-based rating system and operationalized as the t-scaled distance between the participants' task-specific performance estimations and their objective test performance (ΔTSPE). Global metacognition, targeting broader estimates of cognitive functioning (ECF), was quantified by subtracting self- from informant-obtained sum scores on a questionnaire evaluating participants' dysexecutive problems (DEX-DS). Within-group and between-group differences in ΔTSPE and DEX-DS scores were compared non-parametrically, focusing on post-LP changes. RESULTS: Averaged ΔTSPE was higher in the patient groups and mirrored the groups' lower objective test performance, while averaged DEX-DS showed no group difference. Following LP, group comparisons revealed iNPH-specific decrease in both RACD measures. CONCLUSION: Our study revealed LP-related RACD changes in iNPH patients compared to those in AACS and HC participants. The results suggest a mitigation of impaired metacognitive abilities in iNPH, possibly resulting from LP-induced improvements in (local) metacognitive performance, facilitating ECF adjustment alongside a metacognitively stimulating testing procedure.

Neurofeedback Training in Children with ADHD: A Systematic Review of Personalization and Methodological Features Facilitating Training Conditions.

Objective. Current research on the effectiveness of neurofeedback (NFB) in children with attention-deficit/hyperactivity disorder (ADHD) is divided. Personalized NFB (pNFB), using pre-recorded individual electroencephalogram (EEG) features, is hypothesized to provide more reliable results. Our paper reviews available evidence on pNFB effectiveness and its methodological quality. Additionally, it explores whether other methodological features implying personalization are related to successful NFB. Methods. We conducted a systematic literature review on PubMed, PSYNDEX, PsycInfo and PsycArticles until November, 30, 2023. Studies that focused on pNFB in children with ADHD were selected, deviant studies excluded. Quality ratings by independent raters using Loney's1 criteria were conducted. Pooled effect sizes for NFB effects and methodological features were calculated. Results. Three of 109 studies included personalization and were reviewed in the full-text. In two studies, theta/beta-NFB was personalized using individual alpha peak frequencies (iAPF), whereas in one study, individual beta rhythms were trained. All three studies demonstrated significant short- and long-term improvements in ADHD symptoms, as assessed by questionnaires and objective performance tests, when compared to standard protocols (SP), sham-NFB, and control conditions. Twelve of 111 studies reported methodological features consistently related to NFB effectiveness. These features, including self-control instructions, feedback animations, timing of feedback presentation, behavioral performance, pre-recorded individual ERP-components and stimulant medication dosage, can be used to personalize NFB and enhance training success. Conclusion. Personalizing NFB with iAPF appears promising based on the existing -albeit small- body of research. Future NFB studies should include iAPF and other personalized features facilitating implementation consistently associated with treatment success.

Integrative-interpersonal dynamic therapy for poststroke depression (INID): study protocol of a randomised controlled pilot trial.

INTRODUCTION: Depression is the most frequent psychiatric disorder following stroke, affecting about one-third of stroke survivors. Patients experience poorer recovery, lower quality of life and higher mortality compared with stroke survivors without depression. Despite these well-known malign consequences, poststroke depression (PSD) is regarded underdiagnosed and undertreated. Evidence of beneficial effects of psychotherapy to treat PSD remains scarce and inconclusive and is limited by heterogeneity in design, content and timing of the intervention. This pilot study aims to assess the feasibility of a newly developed integrative-interpersonal dynamic PSD intervention in an outpatient setting and provide a first estimation of the potential effect size as basis for the sample size estimation for a subsequent definite trial. METHOD AND ANALYSIS: Patients will be recruited from two German stroke units. After discharge from inpatient rehabilitation, depressed stroke survivors will be randomised to short-term psychotherapy (12 weeks, ≤16 sessions) or enhanced treatment as usual. The manualised psychotherapy integrates key features of the Unified Psychodynamic and Cognitive-Behavioural Unified Protocol for emotional disorders and was adapted for PSD. Primary endpoints are recruitment feasibility and treatment acceptability, defined as a recruitment rate of ≥20% for eligible patients consenting to randomisation and ≥70% completion-rate of patients participating in the treatment condition. A preliminary estimation of the treatment effect based on the mean difference in Patient Health Questionnaire-9 (PHQ-9) scores between intervention and control group six months poststroke is calculated. Secondary endpoints include changes in depression (PHQ-9/Hamilton Depression Scale) and anxiety (Generalised Anxiety Disorder 7) of all participants across all follow-ups during the first year poststroke. ETHICS AND DISSEMINATION: The INID pilot study received full ethical approval (S-321/2019; 2022-2286_1). Trial results will be published in a peer-reviewed journal in the first half of 2025. One-year follow-ups are planned to be carried out until summer 2025. TRIAL REGISTRATION NUMBER: DRKS00030378.

Predictors of post-stroke depression: Validation of established risk factors and introduction of a dynamic perspective in two longitudinal studies.

Introduction: Cerebral insults lead in many cases not only to cognitive impairment but also to disturbed emotionality. After stroke, one in three survivors develops a depression which impacts quality of life and rehabilitation. Meta-analyses have identified five main predictors of post-stroke depression (PSD): history of mental disorder, stroke severity, physical disability, cognitive impairment, and social support. However, these five established variables have never been conjointly investigated in a sample of stroke survivors. Therefore, their independent predictive values remain unclear. Moreover, predictors are most often used as time-invariant factors (status scores), neglecting the intraindividual dynamics after stroke. Methods: Our study analyses the data of two prospective longitudinal studies, investigating stroke survivors from two rehabilitation hospitals (N 1 = 273) and one acute care hospital (N 2 = 226). Baseline assessments included the five established predictors and depressive symptoms. After 6 months, depressive symptoms were reassessed in both studies (n 1 = 176, n 2 = 183), and physical disability and social support were reassessed in study 2. The predictivity of the five predictors and the additional predictivity of intraindividual dynamics for PSD were examined in multiple linear regression analyses. Results: History of mental disorder was a risk factor for depressive symptoms after stroke at all measurement times (B = 3.32 to 3.97; p < 0.01). Physical disability was a risk factor at all measurement times (B = -0.09 to -0.03; p < 0.05) except 6 months after rehabilitation. Social support was a protective factor (B = -2.69 to -1.91; p < 0.01) outside the acute phase (R 2 = 0.15-0.39). Intraindividual changes in physical disability and perceived social support were independent predictors of PSD 6 months after the acute phase (B = -0.08/-0.14; p < 0.01), in addition to status scores on established variables (ΔR 2 = 0.08, p < 0.001). Discussion: History of mental disorder, physical disability, and social support are independent predictors of depressive symptoms in the first year post-stroke, also when considered conjointly. Future studies should control for these variables when investigating new predictors of PSD. In addition, intraindividual changes in known predictors after stroke play a relevant role in the pathogenesis of PSD and should be considered in clinical practice and future research.

Return to work and depressive symptoms in young stroke survivors after six and twelve months: cross-sectional and longitudinal analyses.

BACKGROUND: While depression after stroke is common and stroke prevalence globally increases in working age populations, the role of return-to-work (RTW) in the pathogenesis of post-stroke depression (PSD) remains unclear. This study examined if RTW is linked to PSD within the first year after ischemic stroke, independently from established risk factors. METHOD: Stroke survivors (n = 176) in their working age (<65 years) recruited from two rehabilitation clinics were assessed for established risk factors: pre-stroke depression, activities of daily living, stroke severity, cognitive impairment, and social support. RTW and depressive symptoms (Geriatric Depression Scale: GDS-15) were assessed six- and twelve-months post-stroke. Multivariate regression analyses were used to assess the cross-sectional and longitudinal relationship between RTW and GDS-15, while controlling for established PSD risk factors. RESULTS: Successful RTW was independently associated with lower GDS-15 at both measurement occasions (p < .05), next to the absence of pre-stroke depression and higher social support. Stroke severity predicted GDS-15 at twelve months. The predictive value of six-months RTW for subsequent depressive symptoms beyond the influence of established risk factors was ß = -1.73 (p = .09). DISCUSSION: RTW was independently associated with PSD in young stroke survivors within the first-year post-stroke, and exerted a (marginally significant) effect on subsequent depression. Our study highlights the relevance of RTW for young stroke survivors' PSD, beyond the influence of established risk factors. Further assessments examining to what extent fostering RTW contributes to mental well-being after stroke might be promising for PSD prevention, next to evident beneficial economic effects.

Too Much and Too Little: Antidepressant Treatment in Stroke Survivors during the First Year.

BACKGROUND: Post-stroke depression (PSD) is the most frequent mental illness after stroke, affecting about 30% of stroke survivors and hampering rehabilitation outcome. While current guidelines recommend monitored antidepressant treatment (ADT) in PSD, the limited precision between the use and need of ADT in clinical practice remains underassessed and poorly understood. METHODS: Depression according to DSM criteria and ADT was assessed in n = 294 stroke survivors from two German rehabilitation centers about one, six, and twelve months after stroke. At each measurement occasion, PSD and current use of ADT was assessed, leading to four subgroups: PSD (yes/no) and ADT (yes/no). Frequencies of ADT and PSD were examined and analyzed with regard to depression severity (minor/major). Intra-individual trajectories were used to assess the persistence in ADT over- and undertreatment from a longitudinal perspective. RESULTS: After one, 6 and 12 months, 36.7%, 31.1% and 25.5% of stroke survivors fulfilled the criteria for depression. Across all measurement occasions, 53% of depressed stroke survivors did not receive ADT, while 12% of the non-depressed did. ADT between stroke survivors with major or minor depression differed at baseline but not thereafter. Between 15-40% of the depressed without ADT experienced persisting undertreatment and 25-50% the non-depressed with ADT had not fulfilled depression criteria at an earlier time point. CONCLUSIONS: Depression occurred in one in three stroke survivors. Among these, only one in two received ADT, irrespective of PSD severity after discharge. In contrast, one in eight stroke survivors without depressive disorder received ADT, about half of them in the absence of earlier PSD. In conclusion, we found evidence of both under- and overtreatment of PSD with ADT, which emphasizes the need for a more stringent implementation of current PSD guideline recommendations.

The Post-Stroke Depression Risk Scale (PoStDeRiS): Development of an Acute-Phase Prediction Model for Depression 6 Months After Stroke.

BACKGROUND: Depression after stroke is common but often undertreated as increasing depression prevalence and decreasing health care contacts diverge after the event. OBJECTIVE: To develop an acute-phase prediction scale for prognosis of depression 6 months after stroke. METHODS: Participants (N = 226) were consecutively recruited and assessed within the first week after ischemic stroke for history of depression, stroke severity (National Institutes of Health Stroke Scale), and functional independence (Barthel Index). Early depressive symptoms were self-reported via the Patient Health Questionnaire-2 and external-rated by nurses via the Signs of Depression Scale. Six months later, 183 participants were assessed for Diagnostic and Statistical Manual of Mental Disorders, 5th edition diagnosis of depression. Significant predictors of depression were identified in multivariate logistic regression analysis and their coefficients transformed into a risk scale. Measurement precision was identified using receiver operating characteristic curve analysis. RESULTS: Depression was diagnosed in 32 (17.5%) participants 6 months after stroke. History of depression, the Barthel Index, and the Patient Health Questionnaire-2 were significant predictors of depression. Transformation of the coefficients yielded the Post-Stroke Depression Risk Scale that demonstrated good discrimination (area under the receiver operating characteristic curve = 0.84; 95% confidence interval = 0.78/0.90). The optimum cutoff showed a sensitivity of 0.81, a specificity of 0.72, a positive predictive value of 0.38, and a negative predictive value of 0.95. CONCLUSIONS: The Post-Stroke Depression Risk Scale accurately identifies people in the acute phase with low risk of depression 6 months later. While the sensitivity indicates that recognition of people with later depression is adequate, positive results in the acute phase show low predictivity. Clinical and methodological reasons for these results as well as implications for future research to increase case-finding ability are discussed.

Determinants of Antidepressant Treatment and Outpatient Rehabilitation Within the First Year After Stroke.

This study aims to identify individual determinants of antidepressant treatment and outpatient rehabilitation after stroke. People with ischemic stroke (N = 303) recruited at 2 inpatient rehabilitation clinics were included into a prospective longitudinal study with follow-up telephone interviews 6 and 12 months later. Participants reported on their use of antidepressant medication and psychotherapy as well as physical, occupational, speech, and neuropsychological therapy. The use of antidepressants at discharge (n = 65, 23.8%) was predicted by the severity of depressive symptoms, severity of stroke, history of depression, and use of antidepressants at admission (all p < .05, R2= .55). The number of outpatient rehabilitation services used at follow-ups was predicted by higher functional and cognitive impairment, higher education, younger age, severity of depressive symptoms, and lower self-efficacy (all p < .05; R26M = .24, R212M = .49). The relevance of identified determinants for the improvement of treatment rates after stroke is discussed.

Gender differences in post-stroke depression: A longitudinal analysis of prevalence, persistence and predictive value of known risk factors.

Post-stroke depression (PSD) is the most frequent psychiatric condition after stroke with a prevalence of approximately 33%. In the general population, depression is consistently reported to be more frequent in women than in men. Evidence about gender differences in PSD remains inconclusive and it is unknown if established risk factors exert gender-specific influence. The authors examined gender differences in PSD prevalence, persistence and influence of established risk factors using χ 2- and Welch's t-tests and continuous-time structural equation modelling (CT-SEM). Patients (N = 301) from the longitudinal Berlin-PSD-study were assessed six weeks (baseline), and up to four times during the first 2.5 years post-stroke using DSM-5 depression criteria and the Geriatric Depression Scale (GDS). Established risk factors were assessed at baseline. Women showed higher PSD prevalence and severity at baseline (p < .01) but not thereafter (p ≥ .43). CT-SEM analysis revealed that known risk factors predicted depression, yet predictive value and persistence did not differ between genders. Our results showed that established PSD risk factors influence both genders to a similar extent and that in contrast to depression in the general population, gender differences in PSD prevalence and severity disappeared within six months post-stroke. Thus, for reasons yet to be deciphered, gender differences in PSD appear to be time-dependent after stroke.

Managing depressive symptoms in people with mild cognitive impairment and mild dementia with a multicomponent psychotherapy intervention: a randomized controlled trial.

OBJECTIVE: To evaluate the feasibility and effectiveness of the CORDIAL program, a psychosocial intervention consisting of cognitive behavioral therapy (CBT), cognitive rehabilitation, and reminiscence to manage depressive symptoms for people with mild cognitive impairment (MCI) or dementia. DESIGN: We conducted a randomized controlled trial, based on a two-group (intervention and control), pre-/post-intervention design. SETTING: Participants were recruited from five different old age psychiatry and memory clinics at outpatients' hospitals. PARTICIPANTS: Hundred and ninety-eight people with MCI or early-stage dementia were included. INTERVENTION: The intervention group (n = 100) received 11 individual weekly sessions of the CORDIAL program. This intervention includes elements from CBT, cognitive rehabilitation, and reminiscence therapy. The control group (n = 98) received treatment-as-usual. MEASUREMENTS: We assessed Montgomery-Åsberg Depression Rating Scale (MADRS) (main outcome), Neuropsychiatric Inventory Questionnaire, and Quality of Life in Alzheimer's disease (secondary outcomes) over the course of 4 months and at a 10-month follow-up visit. RESULTS: A linear mixed model demonstrated that the depressive symptoms assessed by MADRS were significantly more reduced in the intervention groups as compared to the control group (p < 0.001). The effect persisted for 6 months after the intervention. No significant differences between groups were found in neuropsychiatric symptoms or quality of life. CONCLUSION: Our multicomponent intervention, which comprised 11 individual sessions of CBT, cognitive rehabilitation, and reminiscence therapy, reduced depressive symptoms in people with MCI and dementia.

General self-efficacy as a driving factor of post-stroke depression: A longitudinal study.

Post-stroke depression (PSD) is the most common psychiatric condition after stroke, affecting one third of survivors. Despite identification of meaningful predictors, knowledge about the interplay between these factors remains fragmentary. General self-efficacy (GSE) is closely linked to PSD, yet direction and magnitude of this relationship remains unclear. The authors assessed the relationship between GSE and depression during the first two years post-stroke while controlling for stable inter-individual differences using continuous time (CT) structural equation modelling (SEM). Patients of two German rehabilitation centres (N = 294, mean age = 63.78 years, SD = 10.83) were assessed six weeks after ischemic stroke and at four follow-ups covering two years. GSE Scale and Geriatric Depression Scale (GDS) were used to assess GSE and depression. CT-analysis revealed significantly higher within-person cross-effects of GSE on GDS (a21 = -.29) than vice versa (a12 = -.17). Maximal cross-lagged effects emerged six months post-stroke. Our results show that decreasing GSE led to increasing depressiveness, and only to a smaller extent vice versa. This suggests that fostering GSE by strengthening perceived control after stroke can counter PSD emersion and exacerbation. Six months post-stroke, when patients face social re-integration, programmes focusing on GSE could potentially help to prevent later PSD.

Comparison of Treatment Rates of Depression After Stroke Versus Myocardial Infarction: A Systematic Review and Meta-Analysis of Observational Data.

OBJECTIVE: Depression after stroke and myocardial infarction (MI) is common but often assumed to be undertreated without reliable evidence being available. Thus, we aimed to determine treatment rates and investigate the application of guidelines in these conditions. METHODS: Databases MEDLINE, EMBASE, PsycInfo, Web of Science, CINAHL, and Scopus were systematically searched without language restriction from inception to June 30, 2017. Prospective observational studies with consecutive recruitment reporting any antidepressant treatment in adults with depression after stroke or MI were included. Random-effects models were used to calculate pooled estimates of treatment rates. RESULTS: Fifty-five studies reported 32 stroke cohorts (n = 8938; pooled frequency of depression = 34%, 95% confidence interval [CI] = 29%-38%) and 17 MI cohorts (n = 10,767; pooled frequency of depression = 24%, 95% CI = 20%-28%). In 29 stroke cohorts, 24% (95% CI = 20%-27%) of 2280 depressed people used antidepressant medication. In 15 MI cohorts, 14% (95% CI = 8%-19%) of 2381 depressed people used antidepressant medication indicating a lower treatment rate than in stroke. Two studies reported use of psychosocial interventions, indicating that less than 10% of participants were treated. CONCLUSIONS: Despite the high frequency of depression after stroke and MI and the existence of efficacious treatment strategies, people often remain untreated. Innovative strategies are needed to increase the use of effective antidepressive interventions in patients with cardiovascular disease.

The influence of early depressive symptoms, social support and decreasing self-efficacy on depression 6 months post-stroke.

BACKGROUND: Post-stroke depression (PSD) is the most frequent mental disorder after stroke, affecting about 30% of stroke survivors. Despite extensive research, little is known about the influence of general self-efficacy (GSE) on PSD. We investigated the effect of GSE on depression six months post-stroke while controlling for established risk factors. METHODS: Eighty-eight patients from two rehabilitation centers with first-ever ischemic stroke were assessed around 8 weeks and 6 months after stroke. Baseline assessment included demographic variables, GSE scale, physical disability (Barthel-Index), stroke severity (modified NIH Scale), pre-stroke mental illness, cognitive status (Mini-Mental-State-Test), social support (F-SozU Questionnaire) and depressiveness (Geriatric Depression Scale, GDS). Follow-up assessment included DSM-IV depression, GDS and GSE. The influence of each risk factor on PSD was analyzed by binary hierarchical regression. RESULTS: Baseline depressiveness (OR=1.41, p<.01) and social support (OR=.95, p=.03) predicted PSD. Decreasing GSE was associated with high baseline GSE (r=.51, p<.01) and influenced later PSD (OR=1.39, p<.01). LIMITATIONS: Patients' range of impairment may have been limited as sufficient speech comprehension and capacity for interview participation were required. Causal relationship between decreasing GSE and increasing GDS cannot be assumed based on correlations. DISCUSSION: Decreasing GSE was linked to PSD, especially in patients with high baseline GSE. This effect may be due to dissatisfaction with recovery following high expectations. Early depressive symptoms and low social support predicted PSD. Early screening for depressive symptoms and focusing on self-efficacy might help to prevent later depression.

ERP evidence for own-age effects on late stages of processing sad faces.

Faces convey important information on interaction partners, such as their emotional state and age. Faces of the same age are, according to recent research, preferentially processed. The aim of the present study was to investigate whether the neural processes underlying this own-age effect are influenced by the emotional expression of the face, and to explore possible explanations such as the frequency or quality of contact to own-age versus other-age groups. Event-related potentials were recorded while 19 younger (18-30 years) and 19 older (64-86 years) observers watched younger and older sad and happy faces. Sad but not happy faces elicited higher late positive potential amplitudes for own-age than for other-age faces. This own-age effect was significant for older, but not for younger, observers, and correlated with the quality of contact with the own-age versus the other-age group. This pattern suggests that sad own-age faces are motivationally more relevant.

Manual-based cognitive behavioral and cognitive rehabilitation therapy for young-onset dementia: a case report.

There is a growing attention worldwide to young-onset dementia (YOD) and this group's special challenges and needs. The literature on psychosocial interventions for this population is scarce, and little is known about the specific challenges and benefits of working therapeutically with this group of patients. The aim of this study was to explore if a manual-based structured cognitive behavioral/cognitive rehabilitation program would be beneficial for these patients. One case, a 63-year-old woman with YOD, is presented to illustrate how this intervention can be applied to individual patients to manage depressive symptoms in YOD.

Challenges With Manual-Based Multimodal Psychotherapy for People With Alzheimer's Disease: A Case Study.

Earlier detection of dementia requires increased knowledge of how to help people in the early stages of dementia. However, few studies have focused on how psychotherapy should be adapted to improve the outcome of therapy for people with Alzheimer's disease. The aims of the present study were to identify and to explore possible obstacles encountered during the use of manual-based psychotherapy for people with early-stage Alzheimer's disease. The study found that individual adaptations to the treatment manual were necessary, particularly the modification of memory aids in order to adapt them to patients' functional level and previous experience with modern technology. In addition, caregivers were essential for both treatment and homework completion, while reduced awareness constituted an obstacle for adherence to the manual.

Age-Related Response Bias in the Decoding of Sad Facial Expressions.

Recent studies have found that age is negatively associated with the accuracy of decoding emotional facial expressions; this effect of age was found for actors as well as for raters. Given that motivational differences and stereotypes may bias the attribution of emotion, the aim of the present study was to explore whether these age effects are due to response bias, that is, the unbalanced use of response categories. Thirty younger raters (19-30 years) and thirty older raters (65-81 years) viewed video clips of younger and older actors representing the same age ranges, and decoded their facial expressions. We computed both raw hit rates and bias-corrected hit rates to assess the influence of potential age-related response bias on decoding accuracy. Whereas raw hit rates indicated significant effects of both the actors' and the raters' ages on decoding accuracy for sadness, these age effects were no longer significant when response bias was corrected. Our results suggest that age effects on the accuracy of decoding facial expressions may be due, at least in part, to age-related response bias.

A Two-Phase Pathogenetic Model of Depression after Stroke.

Depression is among the major long-term complications of cerebral stroke. Occurring in about 30% of all stroke survivors, 'poststroke depression' (PSD) is known to be associated with prolonged recovery, reduced quality of life, and increased mortality. Research over the past 25 years has enlarged our knowledge about organic and psychosocial risk factors, but their interaction is still unclear. In this paper, we start by reviewing and discussing pathogenetic PSD models that were proposed in the 1980s and 1990s. Based on these earlier approaches and on longitudinal research published since that time, a biphasic model is proposed that reflects the current knowledge on the emergence of PSD. The model integrates premorbid, stroke-related and psychosocial risk factors contributing to the emergence of PSD within the first 2 years after stroke. The distinction between 'reactive' and 'organic' PSD has been dropped, and groups of well-documented predictors are recommended for future research. Finally, we will outline possible implications of the model for prevention and therapy.

Latent change score modeling as a method for analyzing the antidepressant effect of a psychosocial intervention in Alzheimer's disease.

BACKGROUND: Developing and evaluating interventions for patients with age-associated disorders is a rising field in psychotherapy research. Its methodological challenges include the high between-subject variability and the wealth of influencing factors associated with longer lifetime. Latent change score modeling (LCSM), a technique based on structural equation modeling, may be well suited to analyzing longitudinal data sets obtained in clinical trials. Here, we used LCSM to evaluate the antidepressant effect of a combined cognitive behavioral/cognitive rehabilitation (CB/CR) intervention in Alzheimer's disease (AD). METHODS: LCSM was applied to predict the change in depressive symptoms from baseline as an outcome of the CORDIAL study, a randomized controlled trial involving 201 patients with mild AD. The participants underwent either the CORDIAL CB/CR program or standard treatment. Using LCSM, the model best predicting changes in Geriatric Depression Scale scores was determined based on this data set. RESULTS: The best fit was achieved by a model predicting a decline in depressive symptoms between before and after testing. Assignment to the intervention group as well as female gender revealed significant effects in model fit indices, which remained stable at 6- and 12-month follow-up examinations. The pre-post effect was pronounced for patients with clinically relevant depressive symptoms at baseline. CONCLUSIONS: LCSM confirmed the antidepressant effect of the CORDIAL therapy program, which was limited to women. The effect was pronounced in patients with clinically relevant depressive symptoms at baseline. Methodologically, LCSM appears well suited to analyzing longitudinal data from clinical trials in aged populations, by accounting for the high between-subject variability and providing information on the differential indication of the probed intervention.

Psychosocial interventions in Alzheimer's disease and amnestic mild cognitive impairment: evidence for gender bias in clinical trials.

BACKGROUND: Alzheimer's disease (AD) affects twice as many women as men. Gender differences in symptom profile, living conditions, coping style and response might affect the outcome of psychosocial interventions (PSIs). OBJECTIVES: Our aim was to review gender differences in the available high-quality phase III trials on PSI in AD and amnestic mild cognitive impairment (aMCI) by considering the gender ratio in the investigated samples. DESIGN: Randomized controlled trials published in 2000-2012 were stepwise analyzed by statistically testing the representativeness of the gender ratio and examining reported gender differences. RESULTS: Forty-five studies (62% of 73 studies) reported gender ratios for each subsample and were included. In these studies, females were underrepresented in the control groups. In the 14 studies (19%) reporting analyses of gender differences, women were underrepresented in both intervention and control groups. However, in the six studies (8%) reporting significant gender differences in outcome, gender distribution was in accordance with prevalence rates. CONCLUSION: Current evidence is insufficient for reliable conclusions on gender differences in PSI outcome in AD and aMCI, as 81% of the available clinical trials either not reported the gender ratio of their samples, or underrepresent females. Further research is needed addressing gender differences, and clinical trials should routinely control for gender bias.