Background In the event of a COVID-19-related absence from an outpatient treatment program, patients suffering from dementia and their caregivers were offered support from a distance. The aim was to examine the extent of the participants' burden as well as how the offer was accepted and evaluated. Material and methods All participants (n = 63) were offered supportive telephone contact over a period of 8 weeks at varying frequencies (weekly, fortnightly). In addition patients received cognitive and physical tasks by mail every 2 weeks. In order to examine the acceptance of the support, data collected from clinical routine were included in a treatment observation. Additionally, all participants were asked to evaluate the support retrospectively. Results Out of 63 contacted participants, 45 were included in the treatment observation. The telephone support was very well accepted and a tendency towards higher agreement could be ascertained by caregivers. The experience of burden remained stable at a moderate level for all participants; however, caregivers were significantly more burdened. Conclusion The present treatment observation shows the acceptance of a location-independent psychosocial treatment program for dementia for future pandemics or treatment failure as well as for the routine care, e.g. for patients with restricted mobility or those living in rural areas without direct hospital connection. In particular, our data strengthen the importance of programs for caregivers in order to alleviate their burden.

Zusammenfassung Hintergrund Bei COVID-19 bedingtem Ausfall eines ambulanten Behandlungsprogramms im Rahmen demenzieller Erkrankungen wurden Patient:innen und deren Angehörigen Überbrückungsmaßnahmen auf Distanz angeboten. Ziel war es zu untersuchen, in welchem Maß die Teilnehmer:innen (TN) belastet waren, und wie die Angebote angenommen und bewertet wurden. Material und Methoden Allen TN ( n = 63) wurden über den Zeitraum von 8 Wochen regelmäßige Telefonkontakte in unterschiedlicher Frequenz (wöchentlich, 14-tägig) sowie die Zusendung kognitiver und körperlicher Trainingsaufgaben im Abstand von 2 Wochen angeboten. Um die Akzeptanz der Maßnahmen sowie das Belastungserleben der TN zu erfassen, wurden aus der klinischen Routine erhobene Daten sowie retrospektiv eine schriftliche Befragung der TN in eine Behandlungsbeobachtung einbezogen. Ergebnisse Von 63 kontaktierten TN wurden die Daten von 45 TN eingeschlossen. Die Überbrückungsmaßnahmen wurden durchwegs positiv bewertet, wobei eine tendenziell höhere Zustimmung vonseiten der Angehörigen zu ermitteln war. Bei allen TN blieb das Belastungserleben stabil auf geringem Niveau; Angehörige waren signifikant stärker belastet. Diskussion Die Ergebnisse der vorliegenden Behandlungsbeobachtung sprechen für eine gut durchführbare und ortsunabhängige psychosoziale Behandlungsform im Rahmen demenzieller Erkrankungen. Diese kann sowohl als Überbrückungsmaßnahme für zukünftige pandemiebedingte Behandlungsausfälle als auch für die Routineversorgung (z. B. für mobilitätseingeschränkte oder im ländlichen Raum ohne direkte Klinikanbindung lebende Betroffene) geeignet sein. Daneben zeigt die Studie, wie notwendig es ist, für Angehörige ebenfalls Maßnahmen zu prüfen, um die Belastung zu reduzieren.

Die hohe Zahl populationsbezogener Alternskohortenstudien in Deutschland hat für die Spezifizierung von Risikofaktoren und Prädiktoren für häufige psychische Erkrankungen im Alter, insbesondere für demenzielle Erkrankungen und depressive Störungen, wertvolle Beiträge geleistet. Die Ergebnisse dieser Kohorten bieten die Möglichkeit, spezifische Mechanismen der Entstehung psychischer Erkrankungen im Alter darzustellen und Präventionsansätze für häufige psychische Erkrankungen im Alter zu präzisieren. Demgegenüber steht aber ein relativer Mangel an klinischen Kohortenstudien zur Verlaufsprädiktion und möglichen Markern für individualisierte Therapieinterventionen bei häufigen psychischen Erkrankungen im Alter. Wir stellen ausgewählte Ergebnisse der Kohortenforschung zu psychischen Erkrankungen im Alter vor und diskutieren neuartige Ansätze zur Integration und Harmonisierung populationsbezogener und klinischer Kohortenansätze.

Diagnostic and therapeutic measures in patients with bipolar disorders are significantly different depending on the age of those affected. Given the demographic changes and the fact that approximately one quarter of patients with bipolar disease are in old age, it is important for geriatricians to be aware of the specific aspects of bipolar disease. This review article presents the diagnostics of bipolar disorders in old people. Interactions with somatic comorbidities, which may lead to the occurrence of secondary mania, just to mention one of the characteristics of old age, are elaborated. Furthermore, age-specific differences also necessitate altered or adjusted therapy regimens, which deviate from those of younger patients.

Introduction: The outpatient clinic for geropsychiatric diseases of LVR-University Hospital Essen cooperates with 22 nursing homes and is responsible for their patients with geropsychiatric diseases on-site at these nursing homes. In 2012 four new nursing homes were introduced into this treatment. Methods: The study was accomplished in a pre-post-design covering 256 patients living in nursing homes in Essen. At the beginning of the cooperation demographic data, diagnosis, the psychopharmacological medication, interactions of this medication and the quantity of inappropriate medications for elderly patients were recorded. After six months of supplying by the physicians of the outpatient clinic the data – again – was analyzed. In this survey the two data collecting time points were compared. Results: The supply by the psychiatric physicians of the outpatient clinic led overall to secure the psychiatric diagnoses or to revise non-appropriate diagnoses. The analysis of the interaction risk using the web-based program MediQ shows that the psychiatric care has contributed to an explicit reduction of risk regarding psychopharmacological interaction. Conclusion: The results of the study can demonstrate that the diagnosis is essential for the adequate treatment can thereby affect medication interaction risks and therefore may reduce adverse drug reactions.

Even if more extensively investigated in affective disorders, the serotonergic system is likely to be also implicated in modulating the pathogenesis of schizophrenia, where it closely interacts with the dopaminergic and glutamatergic system. To substantiate this notion, we studied the intensity and dynamics of cellular Ca(2+) responses to serotonin (5-hydoxytryptamine, 5-HT) in peripheral lymphocytes taken from currently non-psychotic schizophrenic patients. To this aim, peripheral lymphocytes were freshly obtained from healthy controls and a naturalistic collective of patients with schizophrenia in remission. Intracellular Ca(2+) responses were recorded in real-time by ratiometric fluorometry after 5-HT or phythaemagglutinin (PHA) stimulation, which served as an internal reference for Ca(2+) responsivity to non-specific stimulation. The intracellular Ca(2+) peak early after applying the 5-HT trigger was significantly elevated in schizophrenic patients. No significant differences of Ca(2+) peak levels were seen in response to stimulation with the mitogenic agent PHA, although responses to 5-HT and PHA were positively correlated in individual patients or controls. In conclusion, the serotonergic response patterns in peripheral lymphocytes from schizophrenic patients seem to be elevated, if employing sensitive tools like determination of intracellular Ca(2+) responses. Our observations suggest that the participation of serotonergic neurotransmitter system in the pathogenesis of schizophrenia may deserve more interest, even if it should only act as a modulator on the main pathology in the dopaminergic and glutamatergic systems. We hope that this pilot study will prompt further studies with larger patient collectives to revisit this question.

A 64-year-old right-handed Caucasian presented with a four-year history of word-finding deficits and otherwise fluent speech production. Neurological examination remained unremarkable apart from the word finding impairment. Likewise, neuropsychological evaluation confirmed significantly reduced semantic word fluency. While brain MRI depicted only discrete anterior temporal atrophy, 18-fluorodeoxyglucose PET showed clear hypometabolism of the anterior temporal pole bilaterally with left predominance. An imaging-supported diagnosis of the semantic variant of primary progressive aphasia was established in close accordance to recently published diagnostic criteria.The PET findings can be regarded as typical for this condition and PET imaging proved helpful to delineate other variants (non-fluent and logopenic) of primary progressive aphasia.

For decades treatment of schizophrenia was restricted to drugs, which mainly target positive symptoms by interfering with the dopaminergic neurotransmission. Since a large body of experimental and clinical data implicate that schizophrenia may primarily be a consequence of an imbalance in the glutamatergic system, specifically the networks containing GABAergic interneurons (γ-amino butyric acid), new drugs modulating glutamatergic neurotransmission are being developed. Targeting this dysfunction may follow different strategies, including application of direct or indirect NMDA (N-methyl-D-aspartate) receptor agonists or drugs modulating the function of metabotropic glutamate receptors. Meanwhile, the first substances have proven to be effective in animal models of schizophrenia and now enter the stage of clinical trials. The most promising data have been obtained in studies employing agonists of the metabotropic glutamate receptor. A choice of these substances is presented in this review.

Due to the demographic developments, diagnosis and treatment, dementia constitutes an increasing medical challenge and is likely to have an increasing socioeconomic impact. Dementia does not reflect a single disease but encompasses a variety of underlying conditions, heterogeneous clinical courses and therapeutic approaches, among which Alzheimer's disease represents the most common cause. Therefore, a thorough differential diagnosis of dementia is of major importance. To date the current diagnosis of dementia according to ICD-10/DMS-IV is based on clinical criteria. In addition, the concept of mild cognitive impairment comprises early cognitive dysfunction without clinically apparent dementia. Alzheimer's disease is more and more conceptualized as a disease continuum with mild cognitive impairment as an early and manifest dementia as the later stage of the disease. This review gives an overview on the current diagnostic approaches and the proposed revisions of diagnostic and research criteria for Alzheimer's disease.

Demenzerkrankungen haben vor dem Hintergrund der demographischen Entwicklung eine zunehmende medizinische wie auch sozioökonomische Bedeutung.

In light of the dramatically increasing prevalence of Alzheimer's disease (AD) to be expected in the future, the development of novel therapeutics, improved differential and early diagnostics, and means for the identification of individuals at risk are urgently needed. At present, instruments for a reliable differential diagnosis in clinical dementia, mild cognitive impairment, or prodromal stages have direct practical implications for differentiating secondary dementias from neurodegenerative conditions and for treatment decisions. It may also be reasonable to enforce the incorporation of biomarkers into clinical studies as surrogate outcome parameters and as an attempt to optimize recruitment criteria. Recently, revised research criteria increasingly rely on the interpretation of biomarker patterns, including neuroimaging and CSF-based neurochemical dementia diagnosis (NDD) in supporting the clinical diagnosis. Here, we review the performance of current core CSF biomarkers (Aβ(42) peptide, total tau protein and phosphorylated tau species) and try to define objectives for prospective markers, also considering blood-based tests, which would increase the acceptance and wide application of NDD. Moreover, we evaluate the role and the limitations of genotyping in the predictive diagnosis of AD.

INTRODUCTION:Here, we present a stem-cell based study on the de-novo generation of beta-III-tubulin-positive neurons after treatment with the classic antipsychotic drug haloperidol or after treatment with the second-generation antipsychotic (SGA) ziprasidone. METHODS:Adult neural stem cells (ANSC) dissociated from the adult mouse hippocampus were expanded in cell culture with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). ANSC differentiated upon withdrawal of EGF and bFGF. RESULTS AND DISCUSSION:Ziprasidone generated significantly more beta-III-tubulin-positive neurons than haloperidol during the differentiation of adult neural stem cells isolated from murine hippocampus (ANSC). We assume that this net increase in neurogenesis by ziprasidone relies on this drug's 5-HT1A receptor affinity, which is not present in the haloperidol molecule, since the inactivation by WAY100621 impeded this process. These data could possibly suggest a clinical relevance for studying antipsychotic drugs in the stem cell paradigm employed in this study.

Here we studied serotonin (5-HT) as key regulator of adult neural stem cell (ANSC) proliferation, since 5-HT and drugs increasing 5-HT have been linked to increased neurogenesis in the dentate gyrus of the hippocampus. In our in-vitro model, we cultured neurospheres derived from mouse hippocampus in serum-free medium containing epidermal (EGF) and type-2 fibroblast growth factor (FGF2). Under the given conditions ANSC express both isoforms of tryptophane-hydroxylase (TPH). Consequently, ANSC production of 5-HT was confirmed by high pressure liquid chromatography (HPLC). Blocking TPH function by para-chlorophenylalanine (PCPA), ANSC proliferation was significantly reduced, which was rescued by adding exogenous 5-HT. Further, 5-HT action was conveyed to the ANSC predominantly by the serotonin receptor subtype 5-HT 1A, as we have shown by antagonising this receptor with WAY100635, a highly selective inhibitor of 5-HT 1A function. To a lesser extent, 5-HT 2C receptor modulated ANSC proliferation as seen by SB206553 driven blockade of this receptor subtype in co-culture experiments. Finally, we proved chemotactic properties of 5-HT on ANSC migration. Taken together, we claim a meaningful serotonergic impact on proliferation, survival, and migration of ANSC, which is mainly mediated by 5-HT 1A receptor.

In a thought experiment we want to test how the emergence of adult neural stem cells could constitute an example for a scientific revolution in the sense of Thomas Kuhn. In his major work, “The structure of scientific revolutions, 3rd edn, University of Chicago Press, Chicago”, Thomas Kuhn, states that scientific progress is not a cumulative process, but new theories appear by a rather revolutionary sequence of events. Kuhn built his theory on landmark events taken from chemistry and physics, lacking examples from biology. Beginning with Ramon y Cajal's famous quote, “no new neurons after birth”, from the early years of the twentieth century, and Reynolds and Weiss's conflicting finding in 1992 of adult neural stem cells giving rise to new neurons, we will test how the finding of neural stem cells in the adult brain matches with Kuhn's theory. The pivotal problem of defining a paradigm will be our main focus, since the emergence of adult neural stem cells has been acclaimed by the scientific community as the rebuttal of Ramon y Cajal's paradigm.

There is evidence for a strong genetic component in the etiology of schizophrenia, as demonstrated by family, twin and adoption studies suggesting a heritability of about 80%. There are several approaches in the search for genetic risk factors such as linkage or association studies. Additionally, much effort was done in refining the phenotype including neuropsychology, neurophysiology, imaging or the generation of animal models. Genes becoming associated with schizophrenia have to be tested for functionality including e.g. metabolomics, transcriptomics, proteomics, generation of transgenic mice, analysis of protein-protein interactions, allele-specific RNA expression analysis, analysis of neuronal and stem cell cultures, as well as post mortem studies and behavioral studies in rodents. This amount of data requires complex data analysis. A system's perspective can help in the analysis of the structural and functional complexity of the brain. New tools will be needed for a more complex and systemic view. The systems biology approach could be a pivotal tool in understanding of complex behavior and diseases in future.

Serotonin (5-HT) is a regulator of morphogenetic activities during early brain development and neurogenesis, including cell proliferation, migration, differentiation, and synaptogenesis. The 5-HT transporter (5-HTT, SLC6A4) mediates high-affinity reuptake of 5-HT into presynaptic terminals and thereby fine-tunes serotonergic neurotransmission. Inactivation of the 5-HTT gene in mice reduces 5-HT clearance resulting in persistently increased concentrations of synaptic 5-HT. In the present study, we investigated the effects of elevated 5-HT levels on adult neurogenesis in the hippocampus of 5-HTT deficient mice, including stem cell proliferation, survival, and differentiation. Using an in vivo approach, we showed an increase in proliferative capacity of hippocampal adult neural stem cells in aged 5-HTT knockout mice (∼14.5 months) compared to wildtype controls. In contrast, in vivo and additional in vitro analyses of younger adult 5-HTT knockout mice (∼7 weeks and ∼3.0 months) did not reveal significant changes in proliferation of neural stem cells or survival of newborn cells. We showed that the cellular fate of newly generated cells in 5-HTT knockout mice is not different with respect to the total number and percentage of neurons or glial cells from wildtype controls. Our findings indicate that elevated synaptic 5-HT concentration throughout early development and later life of 5-HTT deficient mice does not induce adult neurogenesis in adult mice, but that elevated 5-HT levels in aged mice influence stem cell proliferation.