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Objective: This study investigates the functional health trajectories at the end-of-life in nursing home residents with no dementia, mild-to-moderate dementia, and severe dementia. Methods: 45803 deceased residents (mean age 87.49ys ± 7.14ys, 67.6% female, no dementia (N=18993), mild-to-moderate dementia (N=14687), and severe dementia (N=12123)) from 357 nursing homes across Switzerland were included in this retrospective cohort study. Activities of daily living (ADL) scores of the Resident Assessment Instrument - Minimum Dataset (RAI-MDS) were used to assess functional health. Multi-phase growth models spanning 24 months prior to death were calculated as a function of dementia status and severity. Results: The functional health trajectories follow a nonlinear pattern with a long period of mild decline with mean ADL score change of -0.118 points per months (95% CI -0.122 to -0.114) for the no dementia group, followed by a significant terminal drop (mean ADL change of -1.528, 95% CI -1.594 to -1.462) two to three months before death (transition point at -2.221, 95% CI -2.306 to -2.136). Residents with dementia had a steeper pre-terminal decline (-0.026, 95% CI -0.32 to -0.20 for mild-to-moderate dementia, - 0.056, 95% CI -0.062 to -0.051 for severe dementia) and less terminal decline (0.274, CI 0.211 to 0.337 for mild dementia, -0.230 to 0.336 for severe dementia). However, the transition point and the pattern of decline were similar across the dementia groups, though proceeding at different levels. Conclusions: The dynamics of terminal functional health decline in nursing home residents with and without dementia are similar.

BACKGROUND: The Mini Suffering State Examination (MSSE) has been explicitly recommended to assess suffering in dementia patients. This study aimed to develop a German version of the MSSE and assess its psychometric properties involving people with advanced dementia (PAD) in a nursing home setting. METHODS:The MSSE was translated into German, and 95 primary nurses administered it cross-sectionally to 124 PAD in Zurich, Switzerland. The psychometric properties of the German MSSE version were calculated for this population. RESULTS: The mean age of the PAD was 83.3 years (SD = 9.1, range = 55-102 years), and 98 of them (79.0%) were women. The Kuder-Richardson Formula 20 coefficient for the entire scale (0.58), the eight items relating to objective health conditions (0.39), and the professional and family estimation of the patient's suffering (0.64) indicated low internal consistency. A confirmatory factor analysis indicated an unsatisfactory fit to a one-factor structure, with a comparative fit index and root mean square error of approximation of 0.71 and 0.08, respectively, and a Tucker-Lewis index of 0.64. The MSSE total score was significantly but moderately correlated with the total scores of the Symptom Management-End-of-Life with Dementia (SM-EOLD) scale (Pearson's correlation coefficient (r) = -0.44; p < 0.05), the physical suffering scores (r = 0.41; p < 0.05), and the psychological suffering scores (r = 0.55; p < 0.05). CONCLUSIONS: The German version of the MSSE questionnaire did not perform well in the nursing home setting involving PAD. The instrument had low internal consistency, doubtful validity, and could not discriminate between suffering and other distressing symptoms. We do not recommend its use in this population.

Undergraduate psychiatric education is essential for the training of medical students and for their recruitment into psychiatry. A significant shortage of graduates choosing a career in psychiatry has been recently documented, and this trend might have many causes. When medical students have positive experiences of teaching, elective placements and exposure to psychiatric patients, their attitudes towards psychiatry are significantly better. Therefore, there is a need to improve the quality of undergraduate training courses in psychiatry. Innovative teaching strategies are suggested, including the use of movies, virtual reality, simulated patients and multiprofessional training wards.

Proteolytic processing of the amyloid precursor protein (APP) releases the APP intracellular domain (AICD) from the membrane. Bound to the APP adaptor protein Fe65 and the lysine acetyltransferase (KAT) Tip60, AICD translocates to the nucleus. Here, the complex forms spherical condensates at sites of endogenous target genes, termed AFT spots (AICD-Fe65-Tip60). We show that loss of Tip60 KAT activity prevents autoacetylation, reduces binding of Fe65 and abolishes Fe65-mediated stabilization of Tip60. Autoacetylation is a prerequisite for AFT spot formation, with KAT-deficient Tip60 retained together with Fe65 in speckles. We identify lysine residues 204 and 701 of Fe65 as acetylation targets of Tip60. We do not detect acetylation of AICD. Mutation of Fe65 K204 and K701 to glutamine, mimicking acetylation-induced charge neutralization, increases the transcriptional activity of Fe65 whereas Tip60 inhibition reduces it. The lysine deacetylase (KDAC) class III Sirt1 deacetylates Fe65 and pharmacological modulation of Sirt1 activity regulates Fe65 transcriptional activity. A second acetylation/deacetylation cycle, conducted by CBP and class I/II KDACs at different lysine residues, regulates stability of Fe65. This is the first report describing a role for acetylation in the regulation of Fe65 transcriptional activity, with Tip60 being the only KAT tested that supports AFT spot formation.

Cognitive impairment indicates disturbed brain physiology which can be due to various mechanisms including Alzheimer's pathology. Combined functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) recordings (EEG-fMRI) can assess the interplay between complementary measures of brain activity and EEG changes to be localized to specific brain regions. We used a two-step approach, where we first examined changes related to a syndrome of mild cognitive impairment irrespective of pathology and then studied the specific impact of amyloid pathology. After detailed clinical and neuropsychological characterization as well as a positron emission tomography (PET) scans with the tracer 11-[C]-Pittsburgh Compound B to estimate cerebral amyloid deposition, 14 subjects with mild cognitive impairment (MCI) (mean age 75.6 SD: 8.9) according to standard criteria and 21 cognitively healthy controls (HCS) (mean age 71.8 SD: 4.2) were assessed with EEG-fMRI. Thalamo-cortical alpha-fMRI signal coupling was only observed in HCS. Additional EEG-fMRI signal coupling differences between HCS and MCI were observed in parts of the default mode network, salience network, fronto-parietal network, and thalamus. Individuals with significant cerebral amyloid deposition (amyloid-positive MCI and HCS combined compared to amyloid-negative HCS) displayed abnormal EEG-fMRI signal coupling in visual, fronto-parietal regions but also in the parahippocampus, brain stem, and cerebellum. This finding was paralleled by stronger absolute fMRI signal in the parahippocampus and weaker absolute fMRI signal in the inferior frontal gyrus in amyloid-positive subjects. We conclude that the thalamocortical coupling in the alpha band in HCS more closely reflects previous findings observed in younger adults, while in MCI there is a clearly aberrant coupling in several networks dominated by an anticorrelation in the posterior cingulate cortex. While these findings may broadly indicate physiological cha

Background: Some psychiatric patients develop severe and persistent mental illness (SPMI), which, for a variety of reasons, can be therapy-refractory. Sometimes, treatment is not considered helpful by the patients themselves and does not improve their subjective quality of life. Furthermore, many SPMI patients experience compulsory interventions such as seclusion, restraint, or treatment against their will, which can cause harm. Methods: In a cross-sectional survey of 1,311 German-speaking psychiatrists in Switzerland, participants were asked about the care of SPMI patients in general, and about their attitudes with regard to compulsory interventions in particular, using three case vignettes of patients with severe and persistent anorexia nervosa, schizophrenia and depression. Results: Out of 1,311 contacted psychiatrists, 457 (34.9%) returned the completed survey. In general, 91.0% found it important or very important to respect SPMI patients' autonomy in decision making. However, based on three different clinical case vignettes, 36.8% of psychiatrists would act against the wishes of the patient with severe and persistent schizophrenia, 34.1% against the wishes of the patient with severe and persistent depression, and 21.1% against the wishes of the patient with severe and persistent anorexia nervosa, although all patients were stated to have preserved decision-making capacity. With regard to the case vignettes, 41.1% considered compulsory interventions leading to a temporary reduction of quality of life acceptable in the patient with severe and persistent schizophrenia, 39.4% in the patient with severe and persistent depression, and 25.6% in the patient with severe and persistent anorexia nervosa, although it was stated in all three case vignettes that two independent experts ascribed the patients decision-making capacity regarding their illness and further treatment. Conclusions: Many psychiatrists in our sample found themselves in an ethical dilemma between auto

The provision of palliative care in psychiatry and the use of coercion in palliative care are underexplored areas. We report the case of a 65-year-old woman with cerebral metastatic breast cancer who was compulsorily admitted from a specialized palliative care ward to a psychiatric inpatient ward in Zurich, Switzerland. While in specialized inpatient palliative care, the patient had resisted palliative care but was found to lack decision-making capacity for her treatment due to disordered thought process and paranoid delusions. Under our care, which involved coercive treatment in the form of concealed administration of an antipsychotic, the patient's psychiatric symptoms improved. She regained decision-making capacity, was granted discharge from hospital, and ended her life by assisted suicide on the day of discharge.

The majority of people with intellectual disabilities (ID) and psychiatric disorders access mainstream mental health services across Europe. However, only 56% of countries provide postgraduate psychiatric training in ID according to a survey across 42 European countries. We explore the challenges of ID training and make recommendations for education and health policymakers. Keywords: Community Mental Health Teams; education and training; intellectual disability; learning disability; specialty training