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Zusammenfassung. Psychotische Erkrankungen im Alter umfassen ein grosses Spektrum an Ursachen und Manifestationen. Häufig treten sie im Rahmen einer Depression, einer demenziellen Entwicklung, eines Substanz- und Medikamentenmissbrauchs oder eines Delirs auf. Während im Alter neue Erkrankungen auftreten können, erreichen zunehmend auch mehr Personen mit langjährig bestehenden, chronisch psychotischen Störungen das höhere Lebensalter. Neben psychotischen Störungen sind im Alter kognitive und somatische Beeinträchtigungen häufig, weshalb eine Fremdanamnese unverzichtbar ist. Die krankheitsbedingt veränderten Lebensumstände, die Komplexität und die jeweils individuelle Situation gilt es bei der Diagnostik und Therapie zu integrieren. Die vorliegenden Empfehlungen sind unter der Federführung der Schweizerischen Gesellschaft für Alterspsychiatrie und -psychotherapie (SGAP) in Zusammenarbeit mit den akademischen Fachgesellschaften für gerontologische und psychiatrische Pflege des Vereins für Pflegewissenschaft und weiteren Fachverbänden entstanden. Ziel ist es, den aktuellen Stand des Wissens über die psychotischen Erkrankungen im Alter sowie über die Möglichkeiten der Diagnostik und Therapie zusammenzufassen und den interprofessionellen, klinischen Teams in der stationären und ambulanten Versorgung zur Verfügung zu stellen.

In old age, the chronic use of substances such as alcohol and sedatives, and more recently opioids, is a major public health and personal problem. Despite this, relatively little attention has been paid to the disorders associated with the use of these substances. These recommendations have been formulated by the Swiss Society for Elderly Psychiatry and Psychotherapy (SPPA) in collaboration with the Swiss Nurses' Association (SNA) and the Swiss Society for Addiction Medicine (SSAM). They provide a summary of the knowledge about addiction disorders in old age for the benefit of those working with patients, with the aim of strengthening prevention, early detection and appropriate interventions.À l’âge avancé, la consommation chronique de substances comme l’alcool et les sédatifs, et plus récemment les opioïdes, représente un important problème pour les personnes concernées et de santé publique. Malgré cela, relativement peu d’attention a été accordée aux troubles associés à la consommation de ces substances. Les présentes recommandations ont été formulées par la Société suisse de psychiatrie et psychothérapie de la personne âgée (SPPA) en collaboration avec l’Association suisse des infirmières et infirmiers (ASI) et la Société suisse de médecine de l’addiction (SSMA). Elles mettent à la disposition des intervenants auprès des patients un résumé des connaissances au sujet des troubles addictifs à l’âge avancé, avec comme objectif de renforcer la prévention et le dépistage précoce, et des interventions adaptées.

Background: The identification of people at risk of cognitive impairment is essential for improving recruitment in secondary prevention trials of Alzheimer's disease. We aimed to test and qualify a biomarker risk assignment algorithm (BRAA) to identify participants at risk of developing mild cognitive impairment due to Alzheimer's disease within 5 years, and to evaluate the safety and efficacy of low-dose pioglitazone to delay onset of mild cognitive impairment in these at-risk participants. Methods: In this phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled cognitively healthy, community living participants aged 65–83 years from 57 academic affiliated and private research clinics in Australia, Germany, Switzerland, the UK, and the USA. By use of the BRAA, participants were grouped as high risk or low risk. Participants at high risk were randomly assigned 1:1 to receive oral pioglitazone (0·8 mg/day sustained release) or placebo, and all low-risk participants received placebo. Study investigators, site staff, sponsor personnel, and study participants were masked to genotype, risk assignment, and treatment assignment. The planned study duration was the time to accumulate 202 events of mild cognitive impairment due to Alzheimer's disease in White participants who were at high risk (the population on whom the genetic analyses that informed the BRAA development was done). Primary endpoints were time-to-event comparisons between participants at high risk and low risk given placebo (for the BRAA objective), and between participants at high risk given pioglitazone or placebo (for the efficacy objective). The primary analysis included all participants who were randomly assigned, received at least one dose of study drug, and had at least one valid post-baseline visit, with significance set at p=0·01. The safety analysis included all participants who were randomly assigned and received at least one dose of study medication. An efficacy futility analysis was planned for when approximately 33% of the anticipated events occurred in the high-risk, White, non-Hispanic or Latino group. This trial is registered with ClinicalTrials.gov, NCT01931566. Findings: Between Aug 28, 2013, and Dec 21, 2015, we enrolled 3494 participants (3061 at high risk and 433 at low risk). Of those participants, 1545 were randomly assigned to pioglitazone and 1516 to placebo. 1104 participants discontinued treatment (464 assigned to the pioglitazone group, 501 in the placebo high risk group, and 139 in the placebo low risk group). 3399 participants had at least one dose of study drug or placebo and at least one post-baseline follow-up visit, and were included in the efficacy analysis. 3465 participants were included in the safety analysis (1531 assigned to the pioglitazone group, 1507 in the placebo high risk group, and 427 in the placebo low risk group). In the full analysis set, 46 (3·3%) of 1406 participants at high risk given placebo had mild cognitive impairment due to Alzheimer's disease, versus four (1·0%) of 402 participants at low risk given placebo (hazard ratio 3·26, 99% CI 0·85–12·45; p=0·023). 39 (2·7%) of 1430 participants at high risk given pioglitazone had mild cognitive impairment, versus 46 (3·3%) of 1406 participants at high risk given placebo (hazard ratio 0·80, 99% CI 0·45–1·40; p=0·307). In the safety analysis set, seven (0·5%) of 1531 participants at high risk given pioglitazone died versus 21 (1·4%) of 1507 participants at high risk given placebo. There were no other notable differences in adverse events between groups. The study was terminated in January, 2018, after failing to meet the non-futility threshold. Interpretation: Pioglitazone did not delay the onset of mild cognitive impairment. The biomarker algorithm demonstrated a 3 times enrichment of events in the high risk placebo group compared with the low risk placebo group, but did not reach the pre-specified significance threshold. Because we did not complete the study as planned, findings can only be considered exploratory. The conduct of this study could prove useful to future clinical development strategies for Alzheimer's disease prevention studies. Funding: Takeda and Zinfandel.

Recommendations for the Diagnosis and Therapy of Psychotic Disorders in the Elderly

The present document represents the position of Swiss health-care associations, clinical and research centers, research-supporting foundations, and the association Alzheimer Switzerland regarding the care of persons with dementia and Alzheimer’s disease. We claim that dementia is not part of normal aging but a disease developing more frequently in old age; early diagnosis and treatment of dementia is paramount; all patients with dementia have the right to receive state-of-the-art treatments; more intense information, education, and counseling on dementia are necessary; media should provide balanced and fair reporting of scientific discoveries on Alzheimer’s and dementia; all patients with dementia have the right to be treated; anti-dementia drugs should be used and accompanied by listening, compassion, and understanding.

Recommendations for the Prevention, Diagnostics and Therapy of Addiction Disorders in the Elderly

Obwohl der chronische Konsum einzelner Substanzen wie z.B. Alkohol und Sedativa, sowie zunehmend auch Opioide, im Alter ein grosses Problem mit erheblichen Folgeschäden für die Betroffenen darstellt, ist den entsprechenden Störungsbildern bisher wenig Beachtung geschenkt worden. Die vorliegenden Empfehlungen sind unter der Federführung der Schweizerischen Gesellschaft für Alterspsychiatrie- und Psychotherapie (SGAP) in Zusammenarbeit mit dem Schweizer Berufsverband für Pflegefachpersonal (SBK) und der Schweizerischen Gesellschaft für Suchtmedizin (SSAM) entstanden, mit dem Ziel, den aktuellen Stand des Wissens über die Abhängigkeitserkrankungen im Alter sowie über die Möglichkeiten der Diagnostik und Therapie zusammenzufassen und den interprofessionellen, klinischen Teams zur Verfügung zu stellen. Sie sollen helfen, die Prävention und Frühdiagnostik zu stärken, und stellen bewusst die Psychotherapie und pflegerischen Interventionsmöglichkeiten in den Vordergrund., Although the chronic consumption of alcohol and sedatives, and increasingly opioids, represents a major problem in old age with consequential damage for those affected, little attention has been paid to the substance abuse disorders in old age. The aim of the present recommendations, a collaboration work of the Swiss Society for Geriatric Psychiatry and Psychotherapy (SGAP), Swiss Nurses Association (SBK) and Swiss Society of Addiction Medicine (SSAM), is to summarize the current state of knowledge in prevention, diagnostics and therapy of substance abuse disorders in old age for an interprofessional clinical team. They are intended to help strengthen prevention and early diagnosis, and consciously emphasize psychotherapy and nursing intervention options., La consommation chronique à l’âge avancé de substances comme l’alcool et les sédativfs, et plus récemment d’opioïdes, représente un important problème avec des conséquences à court et à long terme. Malgré cela, peu d’attention a été accordée aux troubles associés à la consommation de ces produits. Les présentes recommandations ont été formulées par la Société Suisse de Psychiatrie et Psychothérapie de la Personne Agée (SPPA) en collaboration avec l’Association suisse des infirmières et infirmiers (ASI) et la Société Suisse de Médedine de l’Addicition (SSMA). Elles ont comme objectif de mettre à la disposition des intervenants des connaissances au sujet des troubles addictifs à l’âge avancé et les options préventives, diagnostiques et thérapeutiques. Elles sont sensées renforcer la prévention et le dépistage précoce et mettent en avant les interventions psychothérapeutiques et les soins.

Decision-making capacity (DMC) in aging adults has become increasingly salient as the number of older adults, life expectancy, and the amount of wealth to be transferred from older generations have all increased. The accurate and reliable determination of older adults’ DMC is a particularly important topic given its implication in legal, financial, and health decisions. Based upon the four-ability DMC model promulgated by Appelbaum and Grisso in the 1980’s, a number of MacArthur Competence Assessment Tools have been developed and widely utilized. However, these tools do not include cognitive testing or other sources of objective data and have limited validity in a medico-legal setting, necessitating additional options for the evaluation of DMC. This is significant from the perspective of the patient because they have a vested interest in accurate and objective assessment of their DMC across domains.Given the disparities in the assessment of DMC, the authors propose, through this debate article, that the evaluation of DMC in the aging adult population utilize a combination of traditional interview and domain specific instruments and neuropsychological testing. To achieve a consensus on the issue, medical experts in a number of fields related to capacity evaluation, including psychiatry, neurology, neuropsychology, and general medicine were consulted and recruited as authors. Experts in Swiss law and ethics were also consulted and provided input.A tendency to focus on a single capacity, and in particular, the ability to consent to medical treatment, arose in the literature. Similarly, there are many instruments purporting to evaluate a single capacity (e.g., consenting to medical treatment, managing finances), while other areas important to the evaluation of DMC received little attention (e.g., activities of daily living, the ability to live independently, to marry, to resist undue influence, and to make a will or advanced care directive). Medical and legal experts in the multidisciplinary group agreed that there is a clear need for more consistency across evaluation of DMC domains and that a combined approach of traditional methods and neuropsychological testing provides a more thorough evaluation and better serves the patient.

In October 2019, a Swiss panel of experts met for the Dementia Summit in Brunnen, Switzerland, to discuss the latest scientific findings on basic and clinical research, as well as practical and political approaches to the challenges of dementia disorders in Switzerland. Here, we present the conference summary. To study pathophysiological changes, as well as the underlying mechanism of fluid biomarker changes, excellent experimental approaches, including transgenic mouse models, are available. Current knowledge about presymptomatic disease progression is largely derived from the longitudinal study of individuals with autosomal dominant mutations (Dominantly Inherited Alzheimer Network). Importantly, more than one third of identified dementia risk factors can be modified. For example, sleep disturbances are not only associated with dementia and neurodegeneration in specific brain regions, but also precede cognitive decline and contribute to the development of brain pathology. Regarding the neuropsychological examination of dementia disorders, standardised tests of social cognition, one of the six cognitive domains that must be assessed according to the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders, are missing, but now under development. The most important new therapeutic approach in the treatment of Alzheimer’s disease is the current attempt to prevent β-amyloid accumulation. While until now clinical studies have failed because of side effects or insufficient clinical effectiveness, Biogen recently announced positive results of high doses of aducanumab, a monoclonal antibody against β-amyloid. Other approaches also show promise. In China, sodium oligomannate has been approved to treat Alzheimer's disease. The substance suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression. Assistive technologies for dementia patients can help identify relevant information for care and nursing, as well as measurements for clinical interventions. Dementia patients have a high risk of developing delirium, even in the home environment. Therefore, it is necessary to use and further develop multi-disciplinary and systematic detection and prevention strategies. Homecare models for dementia patients with multidisciplinary teams have been established and evaluated and should be expanded. Dementia is the third-leading cause of death in Switzerland. In palliative care for severe dementia, the improvement of quality of life is of primary importance. The goals of the National Dementia Strategy, to increase the quality of life in those affected and to reduce taboos surrounding the disease, are still unrealised. The need for further national and regional engagement in order to implement the different findings of the strategy has largely been acknowledged, and these implementations have become the core tasks of a national dementia platform.

Zusammenfassung. Die Alzheimer-Krankheit ist die häufigste neurodegenerative Erkrankung und die häufigste Demenzursache. Die heutige Routinediagnostik basiert auf der klinischen Untersuchung, einer kraniellen Bildgebung sowie Laboruntersuchungen zum Ausschluss anderer behandelbarer Ursachen. Je nach Befundkonstellation können ergänzend eine Lumbalpunktion mit Bestimmung von Amyloid-β-, Tau- und phospo-Tau-Proteinen, eine PET-Bildgebung sowie ggfs. weitere Untersuchungen erfolgen. Als symptomatische Therapien stehen verschiedene Acetylcholinesterasehemmer sowie der NMDA-Rezeptor-Antagonist Memantine zur Verfügung. Neue, kurative Therapieansätze sind in der Entwicklung. Führend sind aktuell Immuntherapien, welche gegen Amyloid-β- und Tau-Proteine gerichtet sind. Nach initial enttäuschenden klinischen Resultaten von Amyloid-β Immuntherapien zeigen sich nun bei Therapiebeginn im Frühstadium der Erkrankung erste positive Resultate dieses Ansatzes. Zudem erreichen die ersten Tau-orientierten Immuntherapien die klinischen Phasen 2 und 3, nachdem positive Signale auch bezüglich des kognitiven Verlaufes in Phase 1 vermeldet wurden. Weiter werden über 70 nicht-immunbasierte Therapieansätze in klinischen Studien geprüft. Auch zeigen sich Fortschritte in der Diagnostik. Mit Hilfe spezifischer Liganden können Amyloid-β und Tau im PET dargestellt werden, was wiederum die Differenzierung von Patienten in den Studien zur Therapieentwicklung erleichtert. Nebst technischen Verbesserungen der Liquordiagnostik werden erste blut-basierte Tests entwickelt, welche in Studien bereits eine gute Korrelation mit Liquor- und PET-Befunden erreichen.

In old age, depression is often associated with cognitive impairment, dementia is associated with depressive symptoms, depressive symptoms can precede a dementia syndrome, and depression and dementia can occur together. In addition, depressive disorders increase the risk for the later development of dementia. The current evidence for the benefit of clinical findings, and neuropsychological, neurochemical and imaging biomarkers for the differentiation of dementia and depression, as well as for the prognosis of depression with regard to the risk of dementia is presented. In addition, current pharmacotherapy and psychotherapy of depression in demented patients is summarised. There is an urgent need for research to elucidate clinical and biological features in older people with depressive disorders who are at an increased risk of developing dementia.

Zusammenfassung. Diese Empfehlungen sollen dazu dienen, Fachpersonen das Wissen über die aktuelle Evidenz von Diagnostik und Therapie der Depression im Alter zur Verfügung zu stellen und damit zur frühzeitigen Erkennung und evidenzbasierten Behandlung beizutragen. Da für einige Behandlungsansätze nur rudimentär kontrollierte Studien vorliegen, wird auch das klinische Expertenwissen in die Beurteilung einbezogen. Im diagnostischen Vorgehen wird die besondere Symptomatik der Depression im Alter beleuchtet, auf die Suizidalität eingegangen und werden die häufig vorkommenden somatischen Komorbiditäten hervorgehoben. Auch Hypothesen zur Pathogenese, wie Neuroendokrinologie, Neurodegeneration und vaskuläre Faktoren, werden erläutert. In der Behandlung gilt heute ein integrierter biopsychosozialer Ansatz mit gezielten psychosozialen Interventionen, spezifischer Psychotherapie und einer antidepressiven Pharmakotherapie bei schweren Depressionen als sinnvoll. Daneben kommen auch chronobiologische oder Neurostimulationsverfahren zum Einsatz.

Background Nutrition is an important modifiable risk factor in Alzheimer's disease. Previous trials of the multinutrient Fortasyn Connect showed benefits in mild Alzheimer's disease dementia. LipiDiDiet investigated the effects of Fortasyn Connect on cognition and related measures in prodromal Alzheimer's disease. Here, we report the 24-month results of the trial. Methods LipiDiDiet was a 24-month randomised, controlled, double-blind, parallel-group, multicentre trial (11 sites in Finland, Germany, the Netherlands, and Sweden), with optional 12-month double-blind extensions. The trial enrolled individuals with prodromal Alzheimer's disease, defined according to the International Working Group (IWG)-1 criteria. Participants were randomly assigned (1:1) to active product (125 mL once-a-day drink containing Fortasyn Connect) or control product. Randomisation was computer-generated centrally in blocks of four, stratified by site. All study personnel and participants were masked to treatment assignment. The primary endpoint was change in a neuropsychological test battery (NTB) score. Analysis was by modified intention to treat. Safety analyses included all participants who consumed at least one study product dose. This trial is registered with the Dutch Trial Register, number NTR1705. Findings Between April 20, 2009, and July 3, 2013, 311 of 382 participants screened were randomly assigned to the active group (n=153) or control group (n=158). Mean change in NTB primary endpoint was −0·028 (SD 0·453) in the active group and −0·108 (0·528) in the control group; estimated mean treatment difference was 0·098 (95% CI −0·041 to 0·237; p=0·166). The decline in the control group was less than the prestudy estimate of −0·4 during 24 months. 66 (21%) participants dropped out of the study. Serious adverse events occurred in 34 (22%) participants in the active group and 30 (19%) in control group (p=0·487), none of which were regarded as related to the study intervention. Interpretation The intervention had no significant effect on the NTB primary endpoint over 2 years in prodromal Alzheimer's disease. However, cognitive decline in this population was much lower than expected, rendering the primary endpoint inadequately powered. Group differences on secondary endpoints of disease progression measuring cognition and function and hippocampal atrophy were observed. Further study of nutritional approaches with larger sample sizes, longer duration, or a primary endpoint more sensitive in this pre-dementia population, is needed., published version, peerReviewed

The hippocampus plays an indispensable role in episodic memory, particularly during the consolidation process. However, its precise role in retrieval of episodic memory is still ambiguous. In this study, we investigated the correlation of hippocampal morphometry and the performance in an autobiographical memory task in 27 healthy controls and 24 patients suffering from Alzheimer's disease (AD). Most importantly, correlations were defined separately and comparatively for memory contents with different retrieval frequency in the past. In healthy subjects, memory performance for seldom retrieved autobiographical events was significantly associated with gray matter density in the bilateral hippocampus, whereas this correlation was not present for events with high retrieval frequency. This pattern of findings confirms that retrieval frequency plays a critical role in the consolidation of episodic autobiographical memories, thereby making them more independent of the hippocampal system. In AD patients, on the other hand, successful memory retrieval appeared to be related to hippocampal morphometry irrespective of the contents' retrieval frequency, comprising events with high retrieval frequency, too. The observed differences between patients and control subjects suggest that AD-related neurodegeneration not only impairs the function, but also decreases the functional specialization of the hippocampal memory system, which, thus, may be considered as marker for AD.

Alzheimer's disease - State of the art, and emerging diagnostics and therapeutics Abstract. Alzheimer's disease (AD) constitutes the most prevalent neurodegenerative disorder, and the most frequent cause of dementia. Current diagnostics include a clinical examination, brain imaging, as well as laboratory testing in order to exclude other treatable disorders. Depending on the findings constellation a lumbar puncture with determination of amyloid-β-, tau- and phospho-tau-proteins, PET imaging and if necessary further investigations are performed. Acetylcholineesteraseinhibitors as well as the NMDA-antagonist mematine allow symptomatic treatment of AD. The development of novel curative drugs is now showing considerable progress. After initially frustrating results, immunotherapies addressing amyloid-β pathology are now showing first positive effects when administered early in the disease course. First immunotherapies targeting tau pathology are furthermore reaching phase 2 and 3 trials, after hints of positive clinical effects in phase 1 trials. An additional set of more than 70 trials investigates non-immune mediated treatment strategies. Diagnostic advances include the development of amyloid-PET imaging, where after the amyloid-β-PET, tau-PET imaging is now reaching clinical implementation. In parallel to the technical advances in cerebrospinal fluid diagnostics, first blood-based biomarkers for AD are being developed.Zusammenfassung. Die Alzheimer-Krankheit ist die häufigste neurodegenerative Erkrankung und die häufigste Demenzursache. Die heutige Routinediagnostik basiert auf der klinischen Untersuchung, einer kraniellen Bildgebung sowie Laboruntersuchungen zum Ausschluss anderer behandelbarer Ursachen. Je nach Befundkonstellation können ergänzend eine Lumbalpunktion mit Bestimmung von Amyloid-β-, Tau- und phospo-Tau-Proteinen, eine PET-Bildgebung sowie ggfs. weitere Untersuchungen erfolgen. Als symptomatische Therapien stehen verschiedene Acetylcholinesterasehemmer sowie der NMDA-Rezeptor-Antagonist Memantine zur Verfügung. Neue, kurative Therapieansätze sind in der Entwicklung. Führend sind aktuell Immuntherapien, welche gegen Amyloid-β- und Tau-Proteine gerichtet sind. Nach initial enttäuschenden klinischen Resultaten von Amyloid-β Immuntherapien zeigen sich nun bei Therapiebeginn im Frühstadium der Erkrankung erste positive Resultate dieses Ansatzes. Zudem erreichen die ersten Tau-orientierten Immuntherapien die klinischen Phasen 2 und 3, nachdem positive Signale auch bezüglich des kognitiven Verlaufes in Phase 1 vermeldet wurden. Weiter werden über 70 nicht-immunbasierte Therapieansätze in klinischen Studien geprüft. Auch zeigen sich Fortschritte in der Diagnostik. Mit Hilfe spezifischer Liganden können Amyloid-β und Tau im PET dargestellt werden, was wiederum die Differenzierung von Patienten in den Studien zur Therapieentwicklung erleichtert. Nebst technischen Verbesserungen der Liquordiagnostik werden erste blut-basierte Tests entwickelt, welche in Studien bereits eine gute Korrelation mit Liquor- und PET-Befunden erreichen.

Elderly patients with depression often exhibit severe cognitive impairment. Neuropsychological tests and psychiatric exploration may not differentiate between reversible cognitive deficits due to depression and persistent cognitive impairment due to dementia. Neurofilament light chain (NfL) level in the interstitial fluid following axonal damage is known to be reflected in the easily accessible serum and predestinates this parameter for clinical investigations in search for a biomarker of cognitive deficits. Sixteen depressive patients aged ≥ 60 years were recruited. For comparison, nine cognitively healthy individuals and eight patients with dementia were included in the study. At baseline, venous blood draws were performed in all participants and serum NfL measurements were carried-out. NfL was able to predict a consecutive dementia diagnosis after remission of depressive symptoms. Despite the relatively small number of patients included in this study, we found statistically significant changes in serum NfL levels between the groups that speak in favor of this - admittedly unspecific - biomarker. The fact that serum NfL changes could predict a consecutive dementia diagnosis after remission of depressive symptoms is of clinical importance: It facilitates an earlier diagnosis and more targeted therapy for the patients with affective and cognitive deficits.

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.

Delirium is a frequent condition in patients in a palliative care situation and most often associated with substantial burden or even danger for the persons concerned as well as caregivers and health-care-professionals. Despite the lack of randomized-controlled-trials (RCTs) benzodiazepines and neuroleptic agents are used extensively in palliative care for the pharmacological management of delirium. A focused review for RCTs assessing pharmacotherapy with benzodiazepines and neuroleptics for the treatment of delirium in patients treated in a palliative care or hospice setting published in 2017 was performed in PubMed. A narrative summary of the findings of the RCTs and practical recommendation are presented. Of 42 publications, two RCTs could be included. One trial assessed the use of lorazepam (in addition to haloperidol) in case of agitation, the other placebo or risperidone or haloperidol in delirious palliative care patients. Neither risperidone nor haloperidol were superior compared to placebo, but were associated with higher mortality and morbidity. Lorazepam (along with haloperidol) reduced agitation in patients with delirium compared to placebo (along with haloperidol), but was unable to reduce the severity and incidence of delirium. It is of importance to note that psychopharmacotherapy with antipsychotics is mainly indicated for the hyperactive form of delirium and psychotic symptoms (e.g., delusions or hallucinations) in the hyper- and hypoactive delirium. Severe agitation and aggressivity can be an indication for neuroleptics, when non-pharmacological interventions fail, whereas the use of benzodiazepines has to be limited to critical situations where neuroleptics cannot be applied and cases of delirium due to alcohol withdrawal. Both substances can aggravate, precipitate or mask delirium, result adverse events with substantial distress or unfavorable survival outcomes for the patients. Thus, they should only be used in severely symptomatic patients and the duration of the medication has to be limited in time. When delirium symptoms decay the psychopharmacotherapy has to be tapered. More important than psychopharmacotherapy, the thorough investigation and treatment of potentially reversible causes of delirium (e.g., pharmacotherapy, infection) and the routine identification of patients at risk for delirium along with prophylactic measures are essential. The recently published landmarks RCTs provide moderate evidence to adopt recommendations from other medical specialties (i.e., intensive care, geriatrics) to the field of palliative care.

Objectives Since the advent of imaging techniques, the role of the neuropsychological assessment has changed. Questions concerning everyday functionality became primarily important and, thus, ecologically valid neuropsychological assessments are mandatory. Virtual reality (VR) environments might provide a way of implementing immersive cognitive assessments with a higher degree of everyday-life-related cognitive demands. Method We report on a VR-based episodic memory examination in N = 30 young and N = 18 healthy older adults (HOA) using a kitchen scene. The test procedure was designed to be structurally comparable to clinically used California Verbal Learning Test (CVLT) in terms of repeated learning trials as well as short and long delayed recall measures. Results The results showed that age-related learning and performance decrements were mainly evident in the CVLT but not in the VR-memory examination. Conclusions The ecologically valid VR-memory examination might provide a more accurate "age-fair" estimation of everyday-life-related memory demands in HOA than the frequently and clinically used CVLT. We concluded this from our finding of context-related automatic and effortless activations of deeply experience based encoding and retrieval strategies with regard to everyday-life-related objects in the HOA, which might not be paralleled by learning arbitrary word associations. (PsycINFO Database Record

Zusammenfassung. Die Suizidrate in der Schweiz nimmt im höheren Lebensalter zu. Gerade in dieser Altersgruppe ist die Dunkelzifferproblematik bedeutsam. Suizid im Alter ist ein komplexes und multifaktorielles Geschehen. Besonders gefährdet sind vereinsamte alte Menschen. Hauptrisikofaktor für einen Suizid ist eine Depression, welche sich im Alter oft atypisch präsentiert, als normaler Prozess des Alterns fehlinterpretiert und nicht adäquat behandelt wird. Der konsequenten Erkennung, Prävention und Behandlung dieser Risikofaktoren kommt im Hinblick auf die Suizidprävention im Alter eine besondere Bedeutung zu.

Die bei der psychotherapeutischen ­Behandlung von Depressionen in fruheren Lebensphasen etablierten Verfahren und Techniken konnen prinzipiell fur den Altersbereich ubernommen werden, mussen jedoch grundsatzlich auf notwendige Anpassungen uberpruft werden.

Alzheimer's disease (AD) is characterized by retrograde memory deficits primarily caused by dysfunction of the hippocampal complex. Unresolved questions exist concerning the time course of hippocampal involvement in conscious recollection of declarative knowledge, as reports of temporal gradients of retrograde amnesia have been inconclusive. The aim of this study was to examine whether the extent and severity of retrograde amnesia is mediated by retrieval frequency or, in contrast, whether it depends on the age of the memory according to the assumptions of the main current theories of memory formation. We compared recall of past public events in patients with AD and healthy control (HC) individuals using the Historic Events Test (HET). The HET assesses knowledge about famous public events of the past 60 years divided into four time segments and consists of subjective memory rating, dating accuracy, and contextual memory tasks. Although memory for public events was impaired in AD patients, there was a strong effect of retrieval frequency across all time segments and both groups. As AD and HC groups derived similar benefits from greater retrieval frequency, cortical structures other than the hippocampal complex may mediate memory retrieval. These findings suggest that more frequently retrieved events and facts become more independent of the hippocampal complex and thus better protected against early damage of AD. This could explain why cognitive activity may delay the onset of memory decline in persons who develop AD.

Background Alzheimer's disease (AD) has been linked to a state of cerebral and systemic inflammation. The objective of the present study was to determine whether singular markers or a set of inflammatory biomarkers in peripheral blood allow discrimination between AD patients and healthy controls at the individual level. Methods Using bead based multiplexed sandwich immunoassays, 25 inflammatory biomarkers were measured in 164 serum samples from individuals with early AD and age-matched cognitively healthy elderly controls. The data set was randomly split into a training set for feature selection and classification training and a test set for class prediction of blinded samples (1 : 1 ratio) to evaluate the chosen predictors and parameters. Multivariate data analysis was performed with use of a support vector machine (SVM). Results After selection of sTNF-R1 as most discriminative parameter in the training set, the application of SVM to the independent test dataset resulted in a 90.0% correct classification for individual AD and control subjects. Conclusions We identified sTNF-R1 from a marker set consisting of 25 inflammatory biomarkers, which allowed SVM-based discrimination of AD patients from healthy controls on a single-subject classification level comparably well as biomarker panels with a clinically relevant accuracy and validity. Although larger sample populations will be needed to confirm this diagnostic accuracy, our study suggests that sTNF-R1 in serum-either as singular marker or incorporated into a biomarker panel-could be a powerful new biomarker for detection of AD. In addition, selective inhibition of TNF-R1 function may represent a new therapeutic approach in AD.

Alzheimer's disease (AD) is becoming a growing global problem, and there is an urgent need to identify reliable blood biomarkers of the risk and progression of this condition. A potential candidate is the brain-derived neurotrophic factor (BDNF), which modulates major trophic effects in the brain. However, findings are apparently inconsistent regarding peripheral blood BDNF levels in AD patients vs. healthy people. We thus performed a systematic review and meta-analysis of the studies that have examined peripheral BDNF levels in patients with AD or mild cognitive impairment (MCI) and healthy controls. We searched articles through PubMed, EMBASE, and hand searching. Over a total pool of 2061 potential articles, 26 met all inclusion criteria (including a total of 1584 AD patients, 556 MCI patients, and 1294 controls). A meta-analysis of BDNF levels between early AD and controls showed statistically significantly higher levels (SMD [95 % CI]: 0.72 [0.31, 1.13]) with no heterogeneity. AD patients with a low (

Background Increased beta-secretase 1 (BACE1) activity has consistently been detected in brain tissue and cerebrospinal fluid of subjects with mild cognitive impairment (MCI) and probable Alzheimer's disease (AD) compared with control subjects. The collection of cerebrospinal fluid by lumbar puncture is invasive. We sought to identify the presence of plasma BACE1 activity and determine potential alterations in subjects with MCI with clinical follow-up examinations for 3 years using patients with diagnosed probable AD dementia compared with healthy control subjects. Methods Seventy-five patients with probable AD, 96 individuals with MCI, and 53 age-matched and sex-matched healthy control subjects were recruited from three independent international academic memory clinics and AD research expert centers. Plasma BACE1 activity was measured by a synthetic fluorescence substrate enzyme-linked immunosorbent assay. BACE1 protein expression was assessed by Western blotting using three different antibodies that recognize the epitopes of the N-terminus, C-terminus, and full-length BACE1. Results Compared with healthy control subjects, plasma BACE1 activity (V max ) significantly increased by 53.2% in subjects with MCI and by 68.9% in patients with probable AD. Subjects with MCI who converted to probable AD dementia at follow-up examinations exhibited significantly higher BACE1 activity compared with cognitively stable MCI nonconverters and showed higher levels of BACE1 activity than patients with AD. Conclusions Plasma BACE1 activity is significantly increased in MCI converters and patients with probable AD. The sensitivities and specificities of BACE1 activity for the patients were 84% and 88%, respectively. Our results indicate that plasma BACE1 activity may be a biomarker for AD risk and could predict progression from prodromal to probable AD dementia.

Late-life depression is frequently associated with cognitive impairment. Depressive symptoms are often associated with or even precede a dementia syndrome. Moreover, depressive disorders increase the risk of persistence for mild cognitive impairment and dementia. Here, we present both the current state of evidence and future perspectives regarding the integration and value of clinical assessments, neuropsychological, neurochemical, and neuroimaging biomarkers for the etiological classification of the dementia versus the depression syndrome and for the prognosis of depression relating to dementia risk. Finally, we summarize the existing evidence for both pharmacotherapy and psychotherapy of depression in demented patients. There is an urgent need for large-scale collaborative research to elucidate the role and interplay of clinical and biological features in elderly individuals with depressive disorders who are at elevated risk for developing dementia. To overcome barriers for successful drug development, we propose the introduction of the precision medicine paradigm to this research field.

Alzheimer's disease (AD) is characterized by memory disturbances primarily caused by pathogenic mechanisms affecting medial temporal lobe structures. As proposed by current theories of memory formation, this decrease is mediated by the age of the acquired knowledge. However, they cannot fully explain specific patterns of retrograde amnesia in AD. In the current study we examined an alternative approach and investigated whether the extent and severity of retrograde amnesia in AD is mediated by the frequency of memory retrieval or whether it depends on the mere age of knowledge. We compared recall of autobiographical incidents from three life periods in patients with amnestic mild cognitive impairment (aMCI), patients with early dementia of Alzheimer type (eDAT), and healthy control (HC) individuals using the Autobiographical Memory Interview. Retrieval frequency was operationalized by a paired comparison analysis. In contrast to HC individuals, recall of autobiographical incidents was impaired in patients with aMCI and eDAT following Ribot's gradient, with a reduced memory loss for remote compared to more recent life events. However, there was a strong effect of retrieval frequency on memory performance with frequently retrieved incidents memorized in more detail than less frequently retrieved episodes. Remote memories were recalled more often than recent ones. These findings suggest that more frequently retrieved autobiographical memories generally become more independent of the hippocampal complex and might thus be better protected against early hippocampal damage related to AD. Hence, the extent of retrograde amnesia in AD appears mainly mediated by the frequency of memory retrieval, which could plausibly explain why cognitive activity can effectively delay the onset of memory decline in AD.

Previous studies suggest impairments of physical, mental, and psychic well-being in patients with Hashimoto's thyroiditis (HT), but these impairments have been shown to be independent of thyroid dysfunction. In 64 euthyroid patients with HT, symptomatic distress was assessed with the Symptom Checklist-90-Revised (SCL-90-R), a 90-item multidimensional self-report symptom inventory using a 5-point rating scale. In a subgroup of patients, endocrine testing 3 years prior to the current investigation was available. Anti-thyroid peroxidase antibodies (TPO-Abs) were associated with the three SCL-90-R global indices Global Severity Index (GSI), Positive Symptom Distress Index (PSDI), and Positive Symptom Total (PST) as well as with somatization and obsessive-compulsive symptoms after adjustment for age, gender, and thyroid function as assessed by TSH levels (all p0.05). HT patients positive for TPO-Abs showed poorer results in the three SCL-90-R global indices as well as in the three domains: somatization, obsessive-compulsive symptoms, and depression (all p≤0.02), though the aforementioned associations did not withstand sequential Bonferroni correction for multiple testing. In contrast, TPO-Abs positivity, defined as TPO-Abs100 IU/l, significantly predicted poorer psychosocial well-being in all of the three SCL-90-R global indices after three years, even after correction (all p≤0.02). In conclusion, high TPO-Abs are associated with poor physical and psychological well-being and appear to predict future health perception in HT patients.

Background/Aims: Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain impairment by common neuropsychological testing. Methods: We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer’s disease (EAD). Results: The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Conclusions: Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD.

Pituitary adenomas, even after successful treatment, are associated with cognitive impairments. It is unclear whether these deficits are a consequence of unspecific factors associated with having a chronic illness and whether the cognitive dysfunctions exceed those of other chronically ill patients. Thirty-eight patients with transsphenoidal surgery for pituitary adenomas and 38 patients undergoing L-thyroxine replacement therapy after thyroid surgery were studied neuropsychologically with established tests. Executive function was examined with the Trail-Making Test A and B, working memory with the digit span test, attention with the digit symbol test, verbal memory with the German version of the Auditory Verbal Learning and Memory Test, and general verbal intelligence by a vocabulary test. Attention (p = .007), attentional speed (p = .0004), executive control (p = .04), and working memory (p = .01), were significantly reduced in patients with pituitary adenomas compared with other chronically ill patients. In contrast, no differences were found between the groups for verbal memory (all subtests: p ≥ .06). Patients with successful surgery for pituitary adenomas show also in comparison with other chronically ill patients an increased risk for deficits in certain aspects of cognitive function, including attention and working memory, supporting the relevance of the brain lesion and its treatment for these dysfunctions. (JINS, 2011, 17, 369–375)

The neurotrophin brain-derived neurotrophic factor (BDNF) plays a critical role in neuronal survival, synaptic plasticity, and memory. Several recent studies have demonstrated altered BDNF serum levels in Alzheimer's disease (AD) patients. However, the association of BDNF serum levels with the rate of cognitive decline in AD patients is still unclear. We demonstrate that BDNF serum levels are significantly decreased in AD patients with fast cognitive decline [decrease of Mini-Mental State Examination (MMSE) score >4/yr; n=12] compared to AD patients with slow cognitive decline (decrease of MMSE score ≤4/yr, n=28) and show a significant correlation with the rate of cognitive decline during 1 yr follow-up. These results suggest that higher BDNF serum levels are associated with a slower rate of cognitive decline in AD patients. Further longitudinal studies are necessary to elucidate the kinetics and the potential role of serum BDNF as a surrogate marker of disease progression in AD patients.