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Zusammenfassung Hintergrund In Leitlinien zur Behandlung von psychischen und Verhaltenssymptomen bei Demenz („Behavioral and Psychological Symptoms of Dementia“ [BPSD]) wird empfohlen, Antipsychotika im Falle einer notwendigen Therapie zeitlich begrenzt und in möglichst geringer Dosis einzusetzen. Fragestellung Um das Bewusstsein für die Risiken einer Antipsychotikabehandlung bei Patient:innen mit Demenz und die dadurch begründete Notwendigkeit einer zeitlich begrenzten und möglichst niedrig dosierten Antipsychotikabehandlung zu schärfen, wurden Handlungsempfehlungen zum Deprescribing von Antipsychotika bei Menschen mit Demenz entwickelt. Material und Methoden Die Entwicklung der Handlungsempfehlungen erfolgte in einem mehrstufigen Prozess: 1. Literaturrecherche unter besonderer Würdigung von konsentierten Leitlinienempfehlungen und Ergebnissen einer eigenen Interventionsstudie (READY-Studie), 2. Diskussion und Konsentierung in einem Expert:innengremium, 3. Onlineumfrage von in Deutschland tätigen ärztlichen Demenzexpert:innen. Ergebnisse Aus 51 im ersten Entwurf zusammengestellten Aussagen wurden nach der Diskussion im multiprofessionellen Expert:innengremium 32 Aussagen zum „Deprescribing“ (Reduktion und Ausschleichen) von Antipsychotika formuliert. 25 der 32 Aussagen wurden nach Konsentierung in einer Onlineumfrage durch ärztliche Demenzexpert:innen final übernommen. Diskussion In Deutschland gibt es bislang keine konkreten Empfehlungen zur Vorgehensweise bei Reduktion und Absetzen von Antipsychotika, die zur Behandlung von BPSD bei Menschen mit Demenz eingesetzt werden. Die vorgelegte Arbeit soll als Handlungsempfehlung für Haus- und Fachärzt:innen dienen. Bei den Empfehlungen handelt es sich um keine Leitlinien, sie ersetzen nicht die Eigenverantwortlichkeit der Behandelnden und das individuell notwendige Vorgehen in Abhängigkeit von der Behandlungssituation.

Mental illnesses are among the most common diseases worldwide. Cases of inability to work caused by mental illness are frequent and the related economic burden is immense. A successful reintegration into their work environment of those patients who were on sick leave due to a mental illness is an important prognostic factor for the further course of the disease and helps reducing financial consequences. It was the aim of the present review to give an overview of the status quo of return-to-work interventions in the international literature.Main themes of interventions addressing return to work of persons with mental illnesses are the provision of psychotherapeutic support with or without combining these approaches with work directed interventions. Personal contact of employees, mental healthcare staff and supervisors may be helpful with regard to facilitating return to work.Current return to work interventions are mostly elaborate, extensive and expensive without convincing results regarding work related outcome parameters. A variety of reasons might be responsible for this finding, including heterogeneity of outcomes, a poor definition of return-to-work-interventions and the complexity of the issue (involving multiple stakeholders).

Zusammenfassung Ziel der Studie Erwerbstätige mit einer psychischen Erkrankung haben nach einer psychischen Krise oft massive Schwierigkeiten, ihre Arbeit wiederaufzunehmen. Im Mittelpunkt der Studie steht die Frage, wie Menschen den Übergang zwischen akutpsychiatrischer Klinik und Arbeitsplatz erleben. Methodik Der Studie liegt ein qualitatives Forschungsdesign (Grounded Theory) zugrunde. Zehn narrative Interviews mit erkrankten Arbeitnehmern sowie vier Gruppeninterviews mit professionellen „Rückkehr-Begleitern“ (Return-to-Work-Experten) wurden geführt. Ergebnisse Die vorliegende Analyse zeigt, dass das Zusammenspiel der beteiligten Akteure von enormer Bedeutung ist. Wesentlich ist, wie die Beteiligten den Rückkehrprozess deuten und welche Handlungsaufforderungen infolge dessen an die Beteiligten adressiert werden. Schlussfolgerungen Ein arbeitsplatzbezogenes Entlassmanagement sollte Unterstützungsangebote vorhalten, die an den Erwartungshaltungen der Beteiligten ansetzen und einen gemeinschaftlichen Deutungsprozess fördern bzw. in Gang setzen.

Zusammenfassung Hintergrund Psychische Erkrankungen sind inzwischen die zweithäufigste Ursache für Krankschreibungen und die häufigste Ursache für krankheitsbedingte Verrentungen. Um Jobverluste zu vermeiden sind besondere Interventionen zur Rückkehr an den Arbeitsplatz erforderlich. Ein erfolgreicher Rückkehrprozess kann eine erneute Krankschreibung sowie Erwerbsunfähigkeit verhindern. Zudem kann eine gelingende Rückkehr in den Berufsalltag positiv auf den Genesungsprozess zurückwirken. Internationale Erfahrungen zeigen, dass Return-to-Work-Programme eine wirksame Handlungsoption sind, um Patienten nach längerer Erkrankung nachhaltig wieder ins Arbeitsleben zurückzuführen. Return-to-Work-Programme bilden hinreichende Unterstützungsangebote, um mangelnde Ressourcen (z. B. fehlende Wertschätzung) und Belastungen (z. B. zu hohes Arbeitsvolumen) zu bewältigen. Methode Für die Studie RETURN wurde ein Return-to-Work Konzept für stationär-psychiatrisch behandelte Patienten entwickelt. Ergebnisse Die Intervention besteht aus dem Einsatz von Return-to-Work- Experten, die auf Basis eines Handbuches arbeiten. In klar definierten Modulen werden mit den Patienten während des stationären Aufenthaltes u. a. sozialrechtliche Grundlagen und Einzelheiten des Rückkehrprozesses besprochen sowie schwierige Situationen (z. B. Umgang mit der Offenlegung der Diagnose, Rückkehrgespräch) vorbereitet. Nach Entlassung erfolgt die Weiterbetreuung v. a. im Hinblick auf Erfahrungen am ersten Arbeitstag, Begleitung zu Gesprächen des BEM (Betriebliches Eingliederungsmanagement) und Unterstützung bei etwaigen Schwierigkeiten. Schlussfolgerung Die Ergebnisse der noch laufenden Studie werden zeigen, ob der gewählte methodische Ansatz zu einer Verbesserung der Rückkehr an den Arbeitsplatz führt.

Background: Advanced stages of dementia are characterized by severe cognitive and physical impairment. It has not yet been investigated whether persons with young onset dementia (YOD) and late onset dementia (LOD) differ in advanced disease stages. Objectives: To compare quality of life (QoL) between persons with advanced YOD and LOD; to explore the determinants of QoL; to investigate whether YOD and LOD differ with regard to symptoms and care. Methods: The study was performed in the context of EPYLOGE (IssuEs in Palliative care for persons in advanced and terminal stages of YOD and LOD in Germany). Persons with advanced dementia (PWAD) were assessed and caregivers were interviewed. QoL was measured with the proxy rating Quality of Life in Late Stage Dementia (QUALID) scale. Results: 93 persons with YOD and 98 with LOD were included. No significant differences in QoL were detected. Determinants of QoL were similar in YOD and LOD. Behavioral and psychological symptoms of dementia (BPSD), suffering and other distressing symptoms were associated with a lower QoL. In YOD but not in LOD antipsychotic treatment was associated with low QoL. The group of persons who were younger than 65 years at the time of the study visit experienced significantly more distressing symptoms than older PWAD. Conclusion: Overall, persons with advanced YOD do not appear to be disadvantaged compared to old and oldest PWAD. Special attention, however, must be paid to the group of the very young persons who seem to be particularly vulnerable.

Background: Reported sex distributions differ between frontotemporal dementia (FTD) cohorts. Possible explanations are the evolving clinical criteria of FTD and its subtypes and the discovery of FTD causal genetic mutations that has resulted in varying demographics. Objective: Our aim was to determine the sex distribution of sporadic and genetic FTD cases and its subtypes in an international cohort. Methods: We included 910 patients with behavioral variant frontotemporal dementia (bvFTD; n = 654), non-fluent variant primary progressive aphasia (nfvPPA; n = 99), semantic variant primary progressive aphasia (svPPA; n = 117), and right temporal variant frontotemporal dementia (rtvFTD; n = 40). We compared sex distribution between genetic and sporadic FTD using χ2-tests. Results: The genetic FTD group consisted of 51.2% males, which did not differ from sporadic FTD (57.8% male, p = 0.08). In the sporadic bvFTD subgroup, males were predominant in contrast to genetic bvFTD (61.6% versus 52.9% males, p = 0.04). In the other clinical FTD subgroups, genetic cases were underrepresented and within the sporadic cases the sex distribution was somewhat equal. Conclusion: The higher male prevalence in sporadic bvFTD may provide important clues for its differential pathogenesis and warrants further research.

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.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.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.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.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.HINTERGRUND: In Leitlinien zur Behandlung von psychischen und Verhaltenssymptomen bei Demenz („Behavioral and Psychological Symptoms of Dementia“ [BPSD]) wird empfohlen, Antipsychotika im Falle einer notwendigen Therapie zeitlich begrenzt und in möglichst geringer Dosis einzusetzen.Um das Bewusstsein für die Risiken einer Antipsychotikabehandlung bei Patient:innen mit Demenz und die dadurch begründete Notwendigkeit einer zeitlich begrenzten und möglichst niedrig dosierten Antipsychotikabehandlung zu schärfen, wurden Handlungsempfehlungen zum Deprescribing von Antipsychotika bei Menschen mit Demenz entwickelt.Die Entwicklung der Handlungsempfehlungen erfolgte in einem mehrstufigen Prozess: 1. Literaturrecherche unter besonderer Würdigung von konsentierten Leitlinienempfehlungen und Ergebnissen einer eigenen Interventionsstudie (READY-Studie), 2. Diskussion und Konsentierung in einem Expert:innengremium, 3. Onlineumfrage von in Deutschland tätigen ärztlichen Demenzexpert:innen.Aus 51 im ersten Entwurf zusammengestellten Aussagen wurden nach der Diskussion im multiprofessionellen Expert:innengremium 32 Aussagen zum „Deprescribing“ (Reduktion und Ausschleichen) von Antipsychotika formuliert. 25 der 32 Aussagen wurden nach Konsentierung in einer Onlineumfrage durch ärztliche Demenzexpert:innen final übernommen.In Deutschland gibt es bislang keine konkreten Empfehlungen zur Vorgehensweise bei Reduktion und Absetzen von Antipsychotika, die zur Behandlung von BPSD bei Menschen mit Demenz eingesetzt werden. Die vorgelegte Arbeit soll als Handlungsempfehlung für Haus- und Fachärzt:innen dienen. Bei den Empfehlungen handelt es sich um keine Leitlinien, sie ersetzen nicht die Eigenverantwortlichkeit der Behandelnden und das individuell notwendige Vorgehen in Abhängigkeit von der Behandlungssituation.

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.

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.We used a structured development process for the establishment of a return-to-work intervention for psychiatric inpatients.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.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.Psychische Erkrankungen sind inzwischen die zweithäufigste Ursache für Krankschreibungen und die häufigste Ursache für krankheitsbedingte Verrentungen. Um Jobverluste zu vermeiden sind besondere Interventionen zur Rückkehr an den Arbeitsplatz erforderlich. Ein erfolgreicher Rückkehrprozess kann eine erneute Krankschreibung sowie Erwerbsunfähigkeit verhindern. Zudem kann eine gelingende Rückkehr in den Berufsalltag positiv auf den Genesungsprozess zurückwirken. Internationale Erfahrungen zeigen, dass Return-to-Work-Programme eine wirksame Handlungsoption sind, um Patienten nach längerer Erkrankung nachhaltig wieder ins Arbeitsleben zurückzuführen. Return-to-Work-Programme bilden hinreichende Unterstützungsangebote, um mangelnde Ressourcen (z. B. fehlende Wertschätzung) und Belastungen (z. B. zu hohes Arbeitsvolumen) zu bewältigen.Für die Studie RETURN wurde ein Return-to-Work Konzept für stationär-psychiatrisch behandelte Patienten entwickelt.Die Intervention besteht aus dem Einsatz von Return-to-Work- Experten, die auf Basis eines Handbuches arbeiten. In klar definierten Modulen werden mit den Patienten während des stationären Aufenthaltes u. a. sozialrechtliche Grundlagen und Einzelheiten des Rückkehrprozesses besprochen sowie schwierige Situationen (z. B. Umgang mit der Offenlegung der Diagnose, Rückkehrgespräch) vorbereitet. Nach Entlassung erfolgt die Weiterbetreuung v. a. im Hinblick auf Erfahrungen am ersten Arbeitstag, Begleitung zu Gesprächen des BEM (Betriebliches Eingliederungsmanagement) und Unterstützung bei etwaigen Schwierigkeiten.Die Ergebnisse der noch laufenden Studie werden zeigen, ob der gewählte methodische Ansatz zu einer Verbesserung der Rückkehr an den Arbeitsplatz führt.

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.

Background: End of life symptoms and symptom management as well as the quality of dying (QoD) of persons with advanced dementia (PWAD) have not yet been systematically studied in Germany. Objective: 1) To investigate symptoms, treatment and care at the end of life, advance care planning, and circumstances of death of recently deceased PWAD; 2) To determine whether there are differences between young and late onset dementia (YOD and LOD). Methods: The study was performed in the context of the project EPYLOGE (IssuEs in Palliative care for persons in advanced and terminal stages of Young-onset and Late-Onset dementia in Germany). Closest relatives of recently deceased patients with advanced YOD (N = 46) and LOD (N = 54) living at home or in long term care were interviewed. Results: Circumstances of death, symptoms, and treatment appeared to be similar between YOD and LOD, except that persons with LOD had significantly more somatic comorbidities and were admitted to hospital in the last three months of life more often than persons with LOD. At end of life, 60% of PWAD appeared to be “at peace”. Difficulty swallowing, gurgling, shortness of breath, and discomfort were observed most frequently. Large interindividual differences in suffering and QoD were present. Determinants of QoD were not identified. Conclusion: Our findings suggest that low QoD was caused by inadequate recognition and/or insufficient treatment of burdensome physical and emotional symptoms. PWADs’ needs should be assessed regularly, and strategies focusing on treatment and implementing support for both the patient and caregiver must be established.

GRN haploinsufficiency causes frontotemporal lobar degeneration and results in microglial hyperactivation, lysosomal dysfunction and TDP-43 deposition. To understand the contribution of microglial hyperactivation to pathology we evaluated genetic and pharmacological approaches suppressing TREM2 dependent transition of microglia from a homeostatic to a disease associated state. Trem2 deficiency in Grn KO mice led to a reduction of microglia activation. 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 allowed a complete rescue of elevated levels of TREM2 together with increased shedding and reduction of TREM2 signaling. Furthermore, antibody-treated PGRN deficient hiMGL showed dampened microglial hyperactivation, reduced TREM2 signaling and phagocytic activity, however, lack of rescue of lysosomal dysfunction. Similarly, lysosomal dysfunction, lipid dysregulation and glucose hypometabolism of Grn KO mice were not rescued by TREM2 ablation. Furthermore, NfL, a biomarker for neurodegeneration, was elevated in the Grn/Trem2 KO. These findings suggest that microglia hyperactivation is not necessarily contributing to neurotoxicity, and instead demonstrates that TREM2 exhibits neuroprotective potential in this model.

Objective: The aims of our study were to describe the clinical phenotype and to characterize the cerebral glucose metabolism patterns as measured with fluordesoxyglucose-positron emission tomography (FDG-PET) in symptomatic FTLD-patients with different GRN variants. Methods: For this study, data were included from all patients (n = 10) of a single-center FTLD registry study who had a pathogenic GRN variant and who had undergone a cerebral FDG-PET scan. Results: An overt variability of clinical phenotypes was identified with half of the cases being not unambiguously classifiable into one of the clinical FTLD subtypes. Furthermore, GRN + patients showed a considerable inter-individual variability of FDG uptake pattern. In half of the GRN + patients, metabolic changes expanded from frontal and temporal brain regions to parietal brain regions including the posterior cingulate cortex. Striking asymmetry without a preference for either hemisphere was overt in half of GRN + cases. Conclusion: We conclude that GRN mutations cause variable patterns of neurodegeneration that often exceed the anatomical boundaries of the frontotemporal brain regions and produce clinical syndromes that cannot clearly be classified into one of the subtypes as defined by the diagnostic criteria.

ZusammenfassungIm späteren Verlauf der Parkinson-Krankheit besteht ein hohes Risiko, neben der charakterisierenden motorischen Symptomatik beeinträchtigende kognitive Funktionsstörungen zu entwickeln. Dieser Störungskomplex kann maßgeblich den klinischen Verlauf bei Patienten in fortgeschrittenen Krankheitsstadien bestimmen. Der Artikel umschreibt knapp das pathophysiologische Konzept kognitiver Beeinträchtigungen bei Parkinson. Er benennt relevante Differenzierungen, die Wege zur Diagnose und aktuelle therapeutische Herangehensweisen.

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, e4-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 e4-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.

As a result of a literature-based expert process, this review provides an overview about the principles of palliative care for people with advanced dementia that are relevant for clinical practice. In particular, the indications, impact and aims of palliative care for advanced dementia are described. Life-prolonging measures and management of symptoms at the end of life are discussed. Furthermore, the overview focuses on the legal basis of decision making.

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.

Background: Primary progressive aphasia (PPA) is a rare disorder. Data on health care utilisation and care-relevant symptoms are scarce.Aims: The study aimed at finding out how patients with PPA are cared for, the extent of professional support utilised by family caregivers, and which care-relevant clinical symptoms and signs occur with advanced disease.Method & Procedures: Forty-three family caregivers of patients with PPA were interviewed with a standardised questionnaire.Outcomes & Results: A majority of caregivers cared for the patients at home without any support. More than 40% of the patients were treated with cholinesterase inhibitors or memantine. Only 9% of the patients received speech therapy. In advanced PPA, the majority of patients were unable to communicate and almost all needed 24-hr care. Other neurological symptoms appeared, and a considerable number of patients suffered from moderate or severe somatic illnesses.Conclusion: Future studies are necessary to investigate the reasons why the P...

Hypersomnie – ein übermäßiges Schlafbedürfnis – bedarf einer detaillierten schlafmedizinisch-neurologischen und psychiatrischen Abklärung. Oftmals überlagert das Auftreten vieler Einzelsymptome die Diagnose der Narkolepsie.

Primary progressive aphasia (PPA) is characterized by profound destruction of cortical language areas. Anatomical studies suggest an involvement of cholinergic basal forebrain (BF) in PPA syndromes, particularly in the area of the nucleus subputaminalis (NSP). Here we aimed to determine the pattern of atrophy and structural covariance as a proxy of structural connectivity of BF nuclei in PPA variants. We studied 62 prospectively recruited cases with the clinical diagnosis of PPA and 31 healthy older control participants from the cohort study of the German consortium for frontotemporal lobar degeneration (FTLD). We determined cortical and BF atrophy based on high-resolution magnetic resonance imaging (MRI) scans. Patterns of structural covariance of BF with cortical regions were determined using voxel-based partial least square analysis. We found significant atrophy of total BF and BF subregions in PPA patients compared with controls [F(1, 82) = 20.2, p < .001]. Atrophy was most pronounced in the NSP and the posterior BF, and most severe in the semantic variant and the nonfluent variant of PPA. Structural covariance analysis in healthy controls revealed associations of the BF nuclei, particularly the NSP, with left hemispheric predominant prefrontal, lateral temporal, and parietal cortical areas, including Broca's speech area (p < .001, permutation test). In contrast, the PPA patients showed preserved structural covariance of the BF nuclei mostly with right but not with left hemispheric cortical areas (p < .001, permutation test). Our findings agree with the neuroanatomically proposed involvement of the cholinergic BF, particularly the NSP, in PPA syndromes. We found a shift from a structural covariance of the BF with left hemispheric cortical areas in healthy aging towards right hemispheric cortical areas in PPA, possibly reflecting a consequence of the profound and early destruction of cortical language areas in PPA. peerReviewed

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) (β = 0.266; p < 0.001). In the 1,821 patients diagnosed with dementia due to AD, a positive association between MMSE score and yearIE (β = 0.230; p < 0.001) was revealed. MMSE scores were higher (β = 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.

Melatonin is secreted systemically from the pineal gland maximally at night but is also produced locally in many tissues. Its chronobiological function is mainly exerted by pineal melatonin. It is a feedback regulator of the main circadian pacemaker in the hypothalamic suprachiasmatic nuclei and of many peripheral oscillators. Although exogenous melatonin is approved for circadian rhythm sleep disorders and old-age insomnia, research on endogenous melatonin in humans is hindered by the great interindividual variability of its amount and circadian rhythm. Single case studies on pinealectomized patients report on disrupted but also hypersomnic sleep. This is the first systematic prospective report on sleep with respect to pinealectomy due to pinealocytoma World Health Organization grade I without chemo- or radiotherapy. Before and after pinealectomy, 8 patients completed questionnaires on sleep quality and circadian rhythm (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Morningness-Eveningness Questionnaire), 2 nights of polysomnography, salivary evening melatonin profiles, and qualitative assessment of 2 weeks of actigraphy and sleep logs. Six patients were assessed retrospectively up to 4 years after pinealectomy. Before pinealectomy, all but 1 patient showed an evening melatonin rise typical for indifferent chronotypes. After pinealectomy, evening saliva melatonin was markedly diminished, mostly below the detection limit of the assay (0.09 pg/mL). No systematic change in subjective sleep quality or standard measures of polysomnography was found. Mean pre- and postoperative sleep efficiency was 94% and 95%, and mean sleep-onset latency was 21 and 17 min, respectively. Sleep-wake rhythm during normal daily life did not change. Retrospective patients had a reduced sleep efficiency (90%) and more stage changes, although this was not significantly different from prospective patients. In conclusion, melatonin does seem to have a modulatory, not a regulatory, effect on standard measures of sleep. Study output is limited by small sample size and because only evening melatonin profiles were assessed.

The term frontotemporal lobar degeneration (FTLD) refers to a group of progressive brain diseases, which preferentially involve the frontal and temporal lobes. Depending on the primary site of atrophy, the clinical manifestation is dominated by behavior alterations or impairment of language. The onset of symptoms usually occurs before the age of 60 years, and the mean survival from diagnosis varies between 3 and 10 years. The prevalence is estimated at 15 per 100,000 in the population aged between 45 and 65 years, which is similar to the prevalence of Alzheimer's disease in this age group. There are two major clinical subtypes, behavioral-variant frontotemporal dementia and primary progressive aphasia. The neuropathology underlying the clinical syndromes is also heterogeneous. A common feature is the accumulation of certain neuronal proteins. Of these, the microtubule-associated protein tau (MAPT), the transactive response DNA-binding protein, and the fused in sarcoma protein are most important. Approximately 10% to 30% of FTLD shows an autosomal dominant pattern of inheritance, with mutations in the genes for MAPT, progranulin (GRN), and in the chromosome 9 open reading frame 72 (C9orf72) accounting for more than 80% of familial cases. Although significant advances have been made in recent years regarding diagnostic criteria, clinical assessment instruments, neuropsychological tests, cerebrospinal fluid biomarkers, and brain imaging techniques, the clinical diagnosis remains a challenge. To date, there is no specific pharmacological treatment for FTLD. Some evidence has been provided for serotonin reuptake inhibitors to reduce behavioral disturbances. No large-scale or high-quality studies have been conducted to determine the efficacy of non-pharmacological treatment approaches in FTLD. In view of the limited treatment options, caregiver education and support is currently the most important component of the clinical management.

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.