Loss of TREM2 rescues hyperactivation of microglia, but not lysosomal deficits and neurotoxicity in models of progranulin deficiency.

Haploinsufficiency of the progranulin (PGRN)-encoding gene (GRN) causes frontotemporal lobar degeneration (GRN-FTLD) and results in microglial hyperactivation, TREM2 activation, lysosomal dysfunction, and TDP-43 deposition. To understand the contribution of microglial hyperactivation to pathology, we used genetic and pharmacological approaches to suppress TREM2-dependent transition of microglia from a homeostatic to a disease-associated state. Trem2 deficiency in Grn KO mice reduced microglia hyperactivation. To explore antibody-mediated pharmacological modulation of TREM2-dependent microglial states, we identified antagonistic TREM2 antibodies. Treatment of macrophages from GRN-FTLD patients with these antibodies led to reduced TREM2 signaling due to its enhanced shedding. Furthermore, TREM2 antibody-treated PGRN-deficient microglia derived from human-induced pluripotent stem cells showed reduced microglial hyperactivation, TREM2 signaling, and phagocytic activity, but lysosomal dysfunction was not rescued. Similarly, lysosomal dysfunction, lipid dysregulation, and glucose hypometabolism of Grn KO mice were not rescued by TREM2 ablation. Synaptic loss and neurofilament light-chain (NfL) levels, a biomarker for neurodegeneration, were further elevated in the Grn/Trem2 KO cerebrospinal fluid (CSF). These findings suggest that TREM2-dependent microglia hyperactivation in models of GRN deficiency does not promote neurotoxicity, but rather neuroprotection.

[Development of a Return-to-work Intervention for Psychiatric Inpatients]. / Entwicklung einer Intervention zur Unterstützung von stationär-psychiatrisch behandelten Patienten bei der Rückkehr an den Arbeitsplatz im Rahmen der RETURN-Studie.

OBJECTIVE: Patients with mental illnesses often face difficulties when returning to workplace after an episode of inpatient treatment. Available resources intended to support the return-to-work process are often not used. It was the aim of the present study to develop an intervention that facilitates the implementation of patient support at the interface of in- and outpatient care. METHODS: We used a structured development process for the establishment of a return-to-work intervention for psychiatric inpatients. RESULTS: The intervention consisted of the use of return-to-work experts who worked on the basis of a manual. In clearly defined modules, patients were given information on social law basics and details of the return process. Difficult situations (e. g., dealing with the disclosure of the diagnosis, return interview) were discussed and rehearsed. After discharge, further care took place, above all with regard to experiences on the first working day, accompaniment to discussions with the employer and support with any other upcoming difficulties. CONCLUSION: The results of the ongoing study will show whether the chosen approach actually yields the expected results, namely an improvement of the return-to-work process.

Inappropriate Involvement? Presenting Empirical Insight into the Preparation Phase of Advance Directives of Persons Living with Dementia Under German Legislation.

The scholarly debate on advance directives (ADs) in the context of dementia is mainly built around ethical arguments. Empirical studies that shed light into the realities of ADs of persons living with dementia are few and far between and too little is known about the effect of national AD legislation on such realities. This paper offers insight into the preparation phase of ADs according to German legislation in the context of dementia. It presents results from a document analysis of 100 ADs and from 25 episodic interviews with family members. Findings show that drafting an AD involves family members and different professionals in addition to the signatory, whose cognitive impairment differed considerably at the time of preparing the AD. The involvement of family members and professionals is at times problematic, which prompts the question of how much and what kind of involvement of others turns an AD of a person living with dementia into an AD about a person living with dementia. The results invite policy makers to critically review legislation on ADs from the perspective of cognitively impaired persons, who might find it difficult to protect themselves from inappropriate involvement when completing an AD.

Utility of the Repeat and Point Test for Subtyping Patients With Primary Progressive Aphasia.

BACKGROUND: Primary progressive aphasia (PPA) may present with three distinct clinical sybtypes: semantic variant PPA (svPPA), nonfluent/agrammatic variant PPA (nfvPPA), and logopenic variant PPA (lvPPA). OBJECTIVE: The aim was to examine the utility of the German version of the Repeat and Point (R&P) Test for subtyping patients with PPA. METHOD: During the R&P Test, the examiner reads out aloud a noun and the participants are asked to repeat the word and subsequently point to the corresponding picture. Data from 204 patients (68 svPPA, 85 nfvPPA, and 51 lvPPA) and 33 healthy controls were analyzed. RESULTS: Controls completed both tasks with >90% accuracy. Patients with svPPA had high scores in repetition (mean=9.2±1.32) but low scores in pointing (mean=6±2.52). In contrast, patients with nfvPPA and lvPPA performed comparably in both tasks with lower scores in repetition (mean=7.4±2.7 for nfvPPA and 8.2±2.34 for lvPPA) but higher scores in pointing (mean=8.9±1.41 for nfvPPA and 8.6±1.62 for lvPPA). The R&P Test had high accuracy discriminating svPPA from nfvPPA (83% accuracy) and lvPPA (79% accuracy). However, there was low accuracy discriminating nfvPPA from lvPPA (<60%). CONCLUSION: The R&P Test helps to differentiate svPPA from 2 nonsemantic variants (nfvPPA and lvPPA). However, additional tests are required for the differentiation of nfvPPA and lvPPA.

A bitter pill to swallow - Polypharmacy and psychotropic treatment in people with advanced dementia.

BACKGROUND: Polypharmacy is common in people with dementia. The use of psychotropic drugs (PDs) and other, potentially inappropriate medications is high. The aims of this cross-sectional study were 1) to investigate the use of drugs in people with advanced dementia (PWAD), living at home or in long term care (LTC); 2) to focus on PD use; and 3) to identify determinants of PD use. METHODS: The study was performed in the context of EPYLOGE (IssuEs in Palliative care for people in advanced and terminal stages of YOD and LOD in Germany). 191 PWAD were included. All drugs that were administered at the date of the examination were recorded. Multiple logistic regression analysis identified determinants of PD use. RESULTS: 96% of PWAD received medication with a median number of four drugs. 49.7% received five or more drugs. According to the Beers Criteria 39% of PWAD ≥ 65 years received at least one potentially inappropriate medication. 79% of PWAD were treated with PDs. Older PWAD and PWAD living in LTC facilities received significantly more drugs than younger PWAD, and PWAD living at home, respectively. Dementia etiology was significantly associated with the use of antipsychotics, antidepressants and sedative substances. Place of living was associated with the use of pain medication. Behavioral disturbances were associated with the use of antipsychotics and sedative substances. CONCLUSIONS: To mitigate the dangers of polypharmacy and medication related harm, critical examination is required, whether a drug is indicated or not. Also, the deprescribing of drugs should be considered on a regular basis. TRIAL REGISTRATION: Clinicaltrial.gov, NCT03364179 . Registered 6 December 2017.

[Deprescribing of antipsychotic drugs for dementia : Recommendations for action on dose reduction and discontinuation attempts]. / "Deprescribing" von Antipsychotika bei Demenz : Handlungsempfehlungen zu Dosisreduktion und Absetzversuchen.

BACKGROUND: Guidelines for the treatment of behavioral and psychological symptoms of dementia (BPSD) recommend that if antipsychotics are necessary, these should be used only for a limited time and with the lowest possible dose. OBJECTIVE: In order to raise awareness of the risks of antipsychotic treatment in patients with dementia and the resulting need for time-limited and as low-dose antipsychotic treatment as possible, recommendations for deprescribing of antipsychotics in people with dementia have been developed. MATERIAL AND METHODS: The recommendations were developed in a multistage process: 1. Literature search with special appreciation of agreed guideline recommendations and results of an intervention study (READY study) 2. Discussion and consensus in a panel of experts, 3. Online survey of medical dementia experts working in Germany. RESULTS: From the 51 statements that were initially drafted 32 statements on antipsychotic deprescribing were formulated after the discussion in the multiprofessional expert panel. Of the 32 statements 25 were finally implemented after agreement by the experts in the online survey. DISCUSSION: In Germany, there are so far no specific recommendations for the reduction and discontinuation of antipsychotics used to treat BPSD in people with dementia. The article is intended as recommendations for general practitioners and specialists. The recommendations are not guidelines and do not replace personal responsibility. The individual approach always depends on the individual treatment situation.

Return-to-work-experts for inpatient treatment of patients with mental illnesses- a proof-of-concept-study (RETURN): the study protocol.

BACKGROUND: Patients with mental illnesses often have massive difficulties returning to work after inpatient treatment at a psychiatric clinic and are often at risk of losing their jobs. The psychosocial support for this patient group at the interface of clinic/outpatient care is often insufficient. METHODS/DESIGN: The RETURN-study prospectively assesses and surveys 200 patients with mental disorders in a cluster randomized intervention study, i.e. treatment teams and patients from intervention wards receive a return-to-work (RTW) intervention. Patients in control wards obtain treatment as usual (TAU). Pairs of comparable wards (similar patient population, similar staff density) have been identified and then randomized for control and intervention (n = 14 for each condition). On intervention wards return-to-work experts (RTW experts) who focus treatment on the workplace-related needs of patients with mental illnesses have been established. These RTW experts ensure the use of available resources within the framework of work-related discharge management and should lead to a more successful return to the workplace. The days at work in the year after release will be evaluated in a mixed methods approach as well as the return rate in the year after release, disability days in the year after return, relapse rate after 12 months, cost-benefit ratio of the intervention, analysis of the predictors / barriers for a successful return to the workplace (e.g. psychopathology, cognition, stigma, social-psychiatric support, company support, etc.), possibilities to implement the concept of RTW experts in standard psychiatric care (TAU - treatment as usual), the impact of the RTW experts' approach on the treatment process in standard psychiatric care. DISCUSSION: This approach is already internationally established in the field of somatic rehabilitation and supported employment [Am J Psychiatry 171:1183-90, 2014; Lancet 370:1146-52, 2007; Cochrane Database Syst Rev, doi:10.1002/14651858.CD006237.pub3, 2014]; the innovative aspect of this project is to implement and evaluate it in standard psychiatric care in Germany. This project requires no new interventions to be developed and tested, as the techniques of the case manager/job coach is applied to the field of return to work. TRIAL REGISTRATION: The study was registered in Deutsches Register Klinische Studien searchable via its Meta-registry (http://apps.who.int/trialsearch/), Trial registration number: DRKS00016037, Date of registration: 21/12/2018, URL of trial registry record.

Development and testing of an informative guide about palliative care for family caregivers of people with advanced dementia.

BACKGROUND: Since people with advanced dementia are usually not able to make complex decisions, it is usually the family caregivers, as proxies, who have to decide on treatments and their termination. However, these decisions are difficult for the caregivers to make, as they are often inadequately informed and cannot properly assess the consequences; moreover, they are concerned about harming the sick person. We aimed to first develop an informative booklet about palliative care issues for caregivers of people with advanced dementia. Secondly, we aimed to investigate a change in family caregivers' knowledge regarding palliative care issues and caregivers' involvement in medical and care decisions before and after studying this booklet. METHODS: A first version of the booklet was drafted by an experienced psychiatrist and palliative care specialist based on existing booklets and guidelines; necessary cultural adaptions were taken into consideration. A nominal group process was conducted to develop the informative guide. In order to investigate the acceptance of the booklet and the possibility to implement it, 38 patient-caregiver dyads were recruited, and caregivers were interviewed both before receiving the booklet and after 3 months of receiving the booklet. RESULTS: Experts from various disciplines collaborated on a German booklet for family caregivers of people with advanced dementia as an information aid regarding issues of palliative care. The subsequent test showed that all caregivers had experienced a personal benefit from the booklet. Caregivers had a significant gain of knowledge after provision of the booklet. A large proportion of caregivers who had not previously considered and/or discussed medical topics reported that they had done so within 3 months after obtaining the booklet, or planned to do so in the near future. CONCLUSIONS: The caregivers valued the comprehensible, concise and well-structured information guide on palliative care issues in advanced dementia. They agreed it increases knowledge and prompts decision making and therefore should be developed in many languages and disseminated among family caregivers of people with dementia. TRIAL REGISTRATION: clinicaltrial.gov, NCT03548142. Retrospectively registered 7 June 2018.

Sex Differences in Neuropsychological Test Performance in Alzheimer's Disease and the Influence of the ApoE Genotype.

BACKGROUND: Only few studies exist reporting sex differences in the Alzheimer disease (AD) patients regarding cognitive profile, brain damage, and risk factors. The present study investigated the influence of sex in combination with the Alzheimer risk allele, ε4-allele of apolipoprotein E, on cognitive performance. MATERIALS AND METHODS: We examined the effect of sex and ApoE genotype on a range of neuropsychological markers from the German version of the Consortium to Establish a Registry in Alzheimer's Disease Neuropsychological Battery in a monocentric study of 399 AD patients. RESULTS: Male patients had significantly more years of school and occupational education compared with women. Male AD patients outperformed female patients in tasks of object naming, constructional praxis, and constructional praxis recall. There was no statistically significant interaction effect between sex and ε4-allele of apolipoprotein E for any of the examined variables. CONCLUSIONS: The superiority of healthy men compared with women in tasks of object naming, constructional praxis, and visual memory seems to remain stable when people develop AD, indicating larger cognitive reserves in men. In contrast, findings that cognitively healthy women outperform men in tests of verbal memory and verbal fluency are not stable in AD. Further studies are needed to gain insight in the reasons for sex differences.

IssuEs in Palliative care for people in advanced and terminal stages of Young-onset and Late-Onset dementia in GErmany (EPYLOGE): the study protocol.

BACKGROUND: Scientific research on palliative care in dementia is still underdeveloped. In particular, there are no research studies at all on palliative care issues in young onset dementia (YOD), although significant differences compared to late onset dementia (LOD) are expected. Most studies have focused on persons with dementia in long term care (LTC) facilities but have neglected persons that are cared for at home. We hypothesize that unmet care needs exist in advanced and terminal stages of YOD and LOD and that they differ between YOD and LOD. METHODS/DESIGN: The EPYLOGE-study (IssuEs in Palliative care for people in advanced and terminal stages of Young-onset and Late-Onset dementia in GErmany) aims to prospectively assess and survey 200 persons with YOD and LOD in advanced stages who are cared for in LTC facilities and at home. Furthermore, EPYLOGE aims to investigate the circumstances of death of 100 persons with YOD and LOD. This includes 1) describing symptoms and management, health care utilization, palliative care provision, quality of life and death, elements of advance care planning, family caregivers' needs and satisfaction; 2) comparing YOD and LOD regarding these factors; 3) developing expert-consensus recommendations derived from the study results for the improvement and implementation of strategies and interventions for palliative care provision; 4) and communicating the recommendations nationally and internationally in order to improve and adapt guidelines, to change current practice and to give a basis and perspectives for future research projects. The results will also be communicated to patients and their families in order to counsel and support them in their decision making processes and their dialogue with professional caregivers and physicians. DISCUSSION: EPYLOGE is the first study in Germany that assesses palliative care and end-of-life issues in dementia. Furthermore, it is the first study internationally that focuses on the specific palliative care situation of persons with YOD and their families. EPYLOGE serves as a basis for the improvement of palliative care in dementia. TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov ( NCT03364179 ; Registered: 6. December 2017.

Dissociation in Rating Negative Facial Emotions between Behavioral Variant Frontotemporal Dementia and Major Depressive Disorder.

OBJECTIVE: Features of behavioral variant frontotemporal dementia (bvFTD) such as executive dysfunction, apathy, and impaired empathic abilities are also observed in major depressive disorder (MDD). This may contribute to the reason why early stage bvFTD is often misdiagnosed as MDD. New assessment tools are thus needed to improve early diagnosis of bvFTD. Although emotion processing is affected in bvFTD and MDD, growing evidence indicates that the pattern of emotion processing deficits varies between the two disorders. As such, emotion processing paradigms have substantial potentials to distinguish bvFTD from MDD. DESIGN AND PARTICIPANTS: The current study compared 25 patients with bvFTD, 21 patients with MDD, 21 patients with Alzheimer disease (AD) dementia, and 31 healthy participants on a novel facial emotion intensity rating task. Stimuli comprised morphed faces from the Ekman and Friesen stimulus set containing faces of each sex with two different degrees of emotion intensity for each of the six basic emotions. MEASUREMENTS AND RESULTS: Analyses of covariance uncovered a significant dissociation between bvFTD and MDD patients in rating the intensity of negative emotions overall (i.e., bvFTD patients underrated negative emotions overall, whereas MDD patients overrated negative emotions overall compared with healthy participants). In contrast, AD dementia patients rated negative emotions similarly to healthy participants, suggesting no impact of cognitive deficits on rating facial emotions. CONCLUSIONS: By strongly differentiating bvFTD and MDDpatients through negative facial emotions, this sensitive and short rating task might help improve the early diagnosis of bvFTD.

Trends of patient referral to a memory clinic and towards earlier diagnosis from 1985-2009.

BACKGROUND: It may be assumed that increased public awareness of dementia due to Alzheimer's disease (AD) together with the availability of efficacious treatment will result in diagnostic evaluation at earlier stages of cognitive decline and diagnosis of dementia due to AD at earlier stages. METHODS: All persons that were examined at a university based memory clinic, in Germany, between 1985 and 2009 were included. RESULTS: In the 3,951 persons identified, linear regression analysis revealed a positive association between Mini Mental State Examination (MMSE) score and year of initial examination (yearIE) (ß = 0.266; p < 0.001). In the 1,821 patients diagnosed with dementia due to AD, a positive association between MMSE score and yearIE (ß = 0.230; p < 0.001) was revealed. MMSE scores were higher (ß = 0.195; p < 0.001) after the introduction of cholinesterase inhibitors in Germany in 1997. CONCLUSIONS: Diagnostic evaluation of individuals occurred at progressively earlier stages of cognitive decline. Dementia due to AD was diagnosed at progressively earlier stages, and this trend was associated with the availability of efficacious treatment. This is the first study on changes in patient referral and diagnosis based on a continuous 25 years period.

Irrelevant Interests? A Qualitative Study Into How German Family Surrogates of Persons Living With Dementia Fulfill Their Legal Role as Advocates of an Advance Directive.

BACKGROUND AND OBJECTIVES: German legislation establishes advance directives (ADs) as legally binding instruments that all involved parties need to adhere to. This applies also to family members who have been authorized as official surrogates of the AD's author. As surrogates, they are expected to make sure that the AD is being implemented. Our study aims at uncovering how family members experience their legally assigned role as an advocate of an AD. RESEARCH DESIGN AND METHODS: We conducted 25 episodic interviews with family surrogates of persons living with dementia and used thematic analysis to make sense of our interview data. RESULTS: Family surrogates expressed scepticism toward ADs as instruments for planning end-of-life care. They did not necessarily follow the decisions expressed in the AD. We found cases in which family surrogates intentionally refrained from bringing the ADs to the attention of health care providers as well as cases in which the ADs conflicted with self-related interests of family surrogates. DISCUSSION AND IMPLICATIONS: Our findings lead us to critique the legal construction of family surrogates as advocates of the AD. Family members are directly and enduringly affected by the end-of-life care decisions that the AD sets out and are thus no neutral agents who have no stake in the matter. Expecting them to simply transmit decisions formulated in the AD means expecting them to render their own interests irrelevant-which, arguably, might be too much to ask.

Rationale and Design of the "DIagnostic and Prognostic Precision Algorithm for behavioral variant Frontotemporal Dementia" (DIPPA-FTD) Study: A Study Aiming to Distinguish Early Stage Sporadic FTD from Late-Onset Primary Psychiatric Disorders.

BACKGROUND: The behavioral variant of frontotemporal dementia (bvFTD) is very heterogeneous in pathology, genetics, and disease course. Unlike Alzheimer's disease, reliable biomarkers are lacking and sporadic bvFTD is often misdiagnosed as a primary psychiatric disorder (PPD) due to overlapping clinical features. Current efforts to characterize and improve diagnostics are centered on the minority of genetic cases. OBJECTIVE: The multi-center study DIPPA-FTD aims to develop diagnostic and prognostic algorithms to help distinguish sporadic bvFTD from late-onset PPD in its earliest stages. METHODS: The prospective DIPPA-FTD study recruits participants with late-life behavioral changes, suspect for bvFTD or late-onset PPD diagnosis with a negative family history for FTD and/or amyotrophic lateral sclerosis. Subjects are invited to participate after diagnostic screening at participating memory clinics or recruited by referrals from psychiatric departments. At baseline visit, participants undergo neurological and psychiatric examination, questionnaires, neuropsychological tests, and brain imaging. Blood is obtained to investigate biomarkers. Patients are informed about brain donation programs. Follow-up takes place 10-14 months after baseline visit where all examinations are repeated. Results from the DIPPA-FTD study will be integrated in a data-driven approach to develop diagnostic and prognostic models. CONCLUSIONS: DIPPA-FTD will make an important contribution to early sporadic bvFTD identification. By recruiting subjects with ambiguous or prodromal diagnoses, our research strategy will allow the characterization of early disease stages that are not covered in current sporadic FTD research. Results will hopefully increase the ability to diagnose sporadic bvFTD in the early stage and predict progression rate, which is pivotal for patient stratification and trial design.

Caregiver burden and needs in frontotemporal dementia.

BACKGROUND: It is well known that burden among caregivers of patients with frontotemporal dementia (FTD) is high. However, little is known about the specific problems, the factors that contribute to caregiver burden, and the needs of the FTD caregivers-particularly those needs that are accessible by external support strategies. OBJECTIVE: We developed a standardized questionnaire that addressed burdens, problems, and the actual needs of FTD caregivers. A total of 94 caregivers were interviewed. RESULTS: It appears that changes in the patients' behavior and in the interpersonal relations between caregivers and patients are associated with caregiver depression. The most important needs and requests of the caregivers included information and psychosocial support through educated staff, financial support as well as the education of medical staff about the disease. CONCLUSIONS: Support strategies should focus on information and psychosocial support. Given the low prevalence of FTD, internet- and telephone-based strategies appear suitable.

[Return-to-Work - The Transition after Psychiatric Inpatient Treatment]. / Return-to-Work ­ Übergangsprozesse nach Behandlung in einem psychiatrischen Akutkrankenhaus.

OBJECTIVES: Workers on sick-leave due to a mental illness have enormous problems to return to work. The main objective of the present study is to examine, how individuals experience the transition from the mental health system to their workplace. METHODS: A qualitative research design guided by a grounded theory approach was used. Narrative interviews with ten workers on sick leave and four semi-structured interviews with return-to-work-experts were conducted. RESULTS: Relevant for returning to work is the interplay between the involved persons. Essential is the interpretation of the transition and as a result, which calls for action are made to the participants. CONCLUSION: Clinical interventions for returning to work should focus the support on the expectations of the participants and stimulate a common interpretation.

The cost-utility of a return-to-work intervention in comparison to routine care for patients with mental disorders in Germany: Results from the RETURN project.

BACKGROUND: Only two-thirds of patients admitted to psychiatric wards return to their previous jobs. Return-to-work interventions in Germany are investigated for their effectiveness, but information regarding cost-effectiveness is lacking. This study investigates the cost-utility of a return-to-work intervention for patients with mental disorders compared to treatment as usual (TAU). METHODS: We used data from a cluster-randomised controlled trial including 166 patients from 28 inpatient psychiatric wards providing data at 6- and 12-month follow-ups. Health and social care service use was measured with the Client Sociodemographic and Service Receipt Inventory. Quality of life was measured with the EQ-5D-3L questionnaire. Cost-utility analysis was performed by calculating additional costs per one additional QALY (Quality-Adjusted Life Years) gained by receiving the support of return-to-work experts, in comparison to TAU. RESULTS: No significant cost or QALY difference between the intervention and control groups has been detected. The return-to-work intervention cannot be identified as cost-effective in comparison to TAU. CONCLUSIONS: The employment of return-to-work experts could not reach the threshold of providing good value for money. TAU, therefore, seems to be sufficient support for the target group.

How do employees currently admitted to acute psychiatric inpatient units rate their psychosocial working conditions with the COPSOQ (Copenhagen Psychosocial Questionnaire).

BACKGROUND: In recent years it could be shown that psychosocial working conditions and mental health of employees are closely correlated. One well-established instrument to measure psychosocial stress at work is the COPSOQ (Copenhagen Psychosocial Questionnaire, German Standard Version). It is an 84 item self-rating instrument addressing several domains of psychosocial working conditions and is generally used for risk assessments in companies. AIMS: To examine associations between COPSOQ ratings with clinical features and symptoms of employees who currently suffer from an episode of a mental illness requiring inpatient treatment. METHOD: For 265 inpatients with mental disorders who participated in a cluster randomized trial (RETURN-study) COPSOQ-data were available as part of the baseline data acquisition. These data were compared with the German COPSOQ validation sample of the Freiburg research center for occupational sciences (FFAW; approximately 250,000 participants). For subdomains of the COPSOQ that showed major and significant differences between the two samples regression analyses were done to predict COPSOQ scores within the RETURN-sample. RESULTS: Psychiatric inpatients did not assess their working conditions significantly different compared to the population based FFAW sample. However, with regard to the effects of working conditions (general health, burnout, presenteeism, and intention to leave the job) there were major differences between the two samples with the clinical sample expressing more negative views. In the RETURN sample these were predicted by a greater expression of depressive symptoms. CONCLUSIONS: The linkage between work and mental wellbeing is complex. Mental illness is not necessarily a result of poor working conditions, while good working conditions may not in every case prevent symptoms of bad health, even if such associations exist.

Speech Motor Profiles in Primary Progressive Aphasia.

PURPOSE: Previous research on motor speech disorders (MSDs) in primary progressive aphasia (PPA) has largely focused on patients with the nonfluent/agrammatic variant of PPA (nfvPPA), with few systematic descriptions of MSDs in variants other than nfvPPA. There has also been an emphasis on studying apraxia of speech, whereas less is known about dysarthria or other forms of MSDs. This study aimed to examine the qualitative and quantitative characteristics of MSDs in a prospective sample of individuals with PPA independent of subtype. METHOD: We included 38 participants with a root diagnosis of PPA according to current consensus criteria, including one case with primary progressive apraxia of speech. Speech tasks comprised various speech modalities and levels of complexity. Expert raters used a novel protocol for auditory speech analyses covering all major dimensions of speech. RESULTS: Of the participants, 47.4% presented with some form of MSD. Individual speech motor profiles varied widely with respect to the different speech dimensions. Besides apraxia of speech, we observed different dysarthria syndromes, special forms of MSDs (e.g., neurogenic stuttering), and mixed forms. Degrees of severity ranged from mild to severe. We also observed MSDs in patients whose speech and language profiles were incompatible with nfvPPA. CONCLUSIONS: The results confirm that MSDs are common in PPA and can manifest in different syndromes. The findings emphasize that future studies of MSDs in PPA should be extended to all clinical variants and should take into account the qualitative characteristics of motor speech dysfunction across speech dimensions. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22555534.

Supporting return to work after psychiatric hospitalization-A cluster randomized study (RETURN-study).

BACKGROUND: If people with episodic mental-health conditions lose their job due to an episode of their mental illness, they often experience personal negative consequences. Therefore, reintegration after sick leave is critical to avoid unfavorable courses of disease, longer inability to work, long payment of sickness benefits, and unemployment. Existing return-to-work (RTW) programs have mainly focused on "common mental disorders" and often used very elaborate and costly interventions without yielding convincing effects. It was the aim of the RETURN study to evaluate an easy-to-implement RTW intervention specifically addressing persons with mental illnesses being so severe that they require inpatient treatment. METHODS: The RETURN study was a multi-center, cluster-randomized controlled trial in acute psychiatric wards addressing inpatients suffering from a psychiatric disorder. In intervention wards, case managers (RTW experts) were introduced who supported patients in their RTW process, while in control wards treatment, as usual, was continued. RESULTS: A total of 268 patients were recruited for the trial. Patients in the intervention group had more often returned to their workplace at 6 and 12 months, which was also mirrored in more days at work. These group differences were statistically significant at 6 months. However, for the main outcome (days at work at 12 months), differences were no longer statistically significant (p = 0.14). Intervention patients returned to their workplace earlier than patients in the control group (p = 0.040). CONCLUSIONS: The RETURN intervention has shown the potential of case-management interventions when addressing RTW. Further analyses, especially the qualitative ones, may help to better understand limitations and potential areas for improvement.