Systematic analysis of nonfatal suicide attempts and further diagnostic of secondary injury in strangulation survivors: A retrospective cross-sectional study.

Background and Aims: Data on nonfatal suicide attempts in Germany are sparse. The study aimed to analyze data on nonfatal suicide attempts and consecutive diagnostic steps to identify secondary injuries after strangulation. Methods: All admissions after nonfatal suicide attempt in a large Bavarian psychiatric hospital between 2014 and 2018 were reviewed and the methods were analyzed. Results: A total of 2125 verified cases out of 2801 registered cases of nonfatal suicide attempts were included in further analysis. The most common methods were intoxication (n = 1101, 51.8%), cutting (n = 461, 21.7%), and strangulation (n = 183, 8.6%). Among survivors of strangulation with external neck compression (n = 99, 54.1%), no diagnostic steps were performed in 36 (36.4%) patients and insufficient imaging in 13 (20.6%) patients. Carotid artery dissection was detected in two (4.0%) of 50 patients with adequate neuroimaging. Conclusions: This study provides details on nonfatal suicide attempts in Germany. Slightly more than half of the patients with strangulation underwent adequate diagnostic work-up, with 4.0% being diagnosed with dissection. Further studies with systematic screening for dissection after strangulation in psychiatric hospitals are recommended to reduce possible under-reporting.

Elecsys Cerebrospinal Fluid Immunoassays Accurately Detect Alzheimer's Disease Regardless of Concomitant Small Vessel Disease.

BACKGROUND: Differentiating dementia due to small vessel disease (SVD) from dementia due to Alzheimer's disease (AD) with concomitant SVD is challenging in clinical practice. Accurate and early diagnosis of AD is critical to delivering stratified patient care. OBJECTIVE: We characterized the results of Elecsys® cerebrospinal fluid (CSF) immunoassays (Roche Diagnostics International Ltd) in patients with early AD, diagnosed using core clinical criteria, with varying extent of SVD. METHODS: Frozen CSF samples (n = 84) were measured using Elecsys ß-Amyloid(1-42) (Aß42), Phospho-Tau (181P) (pTau181), and Total-Tau (tTau) CSF immunoassays, adapted for use on the cobas® e 411 analyzer (Roche Diagnostics International Ltd), and a robust prototype ß-Amyloid(1-40) (Aß40) CSF immunoassay. SVD was assessed by extent of white matter hyperintensities (WMH) using the lesion segmentation tool. Interrelations between WMH, biomarkers, fluorodeoxyglucose F18-positron emission tomography (FDG-PET), and other parameters (including age and Mini-Mental State examinations [MMSE]) were assessed using Spearman's correlation, sensitivity/specificity, and logistic/linear regression analyses. RESULTS: The extent of WMH showed significant correlation with Aß42/Aß40 ratio (Rho=-0.250; p = 0.040), tTau (Rho = 0.292; p = 0.016), tTau/Aß42 ratio (Rho = 0.247; p = 0.042), age (Rho = 0.373; p = 0.002), and MMSE (Rho=-0.410; p = 0.001). Sensitivity/specificity point estimates for Elecsys CSF immunoassays versus FDG-PET positivity for underlying AD pathophysiology were mostly comparable or greater in patients with high versus low WMH. WMH were not a significant predictor and did not interact with CSF biomarker positivity but modified the association between pTau181 and tTau. CONCLUSION: Elecsys CSF immunoassays detect AD pathophysiology regardless of concomitant SVD and may help to identify patients with early dementia with underlying AD pathophysiology.

[Insomniac symptoms and suicidality-link and management]. / Insomnische Symptome und Suizidalität ­ Zusammenhänge und Management.

BACKGROUND: A link between insomniac symptoms and suicidality has long been suspected and deserves specific attention. OBJECTIVE: We examine the current evidence for this relationship from epidemiology and neurobiology in order to propose a targeted management. MATERIAL AND METHOD: Clinical example and selective Medline-literature research for insomnia symptoms and suicidality. RESULTS: Epidemiological data and statistical analysis show that symptoms of insomnia are independent risk factors for suicidality. Neurobiological factors associated with combined insomnia symptoms and suicidality are: serotonergic dysfunction and circadian rhythm disorder leading to hypofrontality with reduced problem solving capacity and impaired emotional and impulse-control. Social isolation, recurrent rumination, comorbid psychiatric disorders, access to potentially lethal drugs or weapons need urgent evaluation in patients with a combination of suicidality and symptoms of insomnia. CONCLUSION: patients with insomnia and further risk factors for suicide need to be treated resolutely and at an early stage. Modern sleep-promoting antidepressants with low toxicity and antipsychotics must be preferred in the treatment of patients with insomniac sleep disorders and suicidality. Multimodal anti-insomnia and anti-depressive therapy adapted to the circadian rhythm can exert a favorable influence both on depressive-suicidal and insomnia symptoms and their inherent risks.

[Richard Semon (1859-1918): expeditions, engrams and epigenetics]. / Richard Semon (1859­1918): Expeditionen, Engramme und Epigenetik.

Richard Semon (1859-1918) was a student of Ernst Haeckel and began his career as a zoologist with work on sea urchins, starfish, chicken and lung fish, which he collected at the Mediterranean Sea and in Australia. After his return to Germany he was forced to leave Jena and the university due to private reasons, and settled in Munich, where Semon devoted most of his time to the more philosophical aspects of biology, developed the theory of "mneme" (1904), which he extended towards the inheritance of acquired characteristics (1912). Semon's concept of memory reached far beyond the brain and the individual person. In 1918 he took his life, despondent because of a surmised lack of scientific appreciation, the death of his beloved wife, the political turmoil at the end of WWI, and his-the memory researcher's-suspected loss of memory. Eight years later, the experimental biologist Paul Kammerer (1880-1926) from Vienna, Semon's must trusted source for the inheritance of acquired characteristics, also shot himself. Serious doubts increasingly overshadowed his work on salamanders and midwife toads. Epigenetics, the nature of memory, the fear of cognitive impairment, depression, the impact of private and political matters on scientific work, suspected scientific errors, fraud and a scientists' suicides are condensed in Semon's life and death.

Herpes simplex virus alters Alzheimer's disease biomarkers - A hypothesis paper.

INTRODUCTION: Human herpes simplex virus 1 (HSV1) is discussed to induce amyloid-ß (Aß) accumulation and neurofibrillary tangles of hyperphosphorylated tau (pTau) in Alzheimer's disease (AD) in cell culture and animal models. Aß appears to be virostatic. We investigated the association between intrathecal antibodies against HSV or cytomegalovirus (CMV) and cerebrospinal fluid (CSF) AD biomarkers. METHODS: Aß42 /Aß40 ratio, pTau, and tTau were measured in CSF of 117 patients with early AD positive for amyloid pathology (A+) and 30 healthy controls (A-). CSF-to-serum anti-HSV1/2-IgG antibody indices (AI-IgGHSV1/2 ) and CMV (AI-IgGCMV ) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Exclusively in HSV1-seropositive AD, pTau was positively and significantly predicted by AI-IgGHSV1/2 and negatively by the Aß42 /Aß40 ratio in both univariate and multivariate regression analyses. Furthermore, a significant and negative interaction between the AI-IgGHSV1/2 and Aß42 /Aß40 ratio on pTau was found. DISCUSSION: The results support the hypothesis that HSV infection contributes to AD. HIGHLIGHTS: HSV antibody index is positively associated with tau pathology in patients with AD. HSV antibody index is negatively associated with cerebral FDG metabolism. Amyloid modulates the association of HSV antibody index with CSF-pTau. HSV in AD offers a pathophysiological model connecting tau and amyloid.

[Mild cognitive impairment in geriatric practice: patient orientation, diagnostics, treatment and ethics]. / Leichte kognitive Beeinträchtigung (MCI) in der altersmedizinischen Praxis: Patientenorientierung, Diagnostik, Behandlung und Ethik.

Mild cognitive impairment (MCI) is a common problem in old people, which can be distressing for patients and their families. The main feature of MCI is a decrease in cognitive performance with activities of daily living still unimpaired. The identification of treatable risk factors, recognition of early cognitive changes and a timely differential diagnosis, comprehensive information and counselling are important tasks in geriatric medicine. The aim of this article is to present practical recommendations to support physicians working with geriatric patients in recognizing cognitive deficits at an early stage, provide high-quality care focusing on counselling, treatment, and comorbidity management and to maximize the potential of the available treatment options.

[Mathilde Ludendorff (1877-1966): specialist for nervous and mental diseases and Germanic philosopher]. / Mathilde Ludendorff (1877­1966): Nervenärztin und völkische Philosophin.

Mathilde Ludendorff (nee Spiess, widowed von Kemnitz, divorced Kleine) was one of the first women who studied medicine in Imperial Germany. She wrote a feminist doctoral thesis, refuted Sigmund Freud's psychoanalysis early in her career, detected the fraud of Albert von Schrenck-Notzing's spiritualist research, became a specialist for nervous and mental diseases after only 17 months of training with Emil Kraepelin, as his-according to her own words-best pupil, treated General Ludendorff's first wife and soon became his second, developed a Germanic philosophy too radical for Adolf Hitler's taste, was considered as a primary culprit after a first denazification trial in 1949 and contested the expert opinion of her colleague Professor Georg Stertz about her own mental state. Her books are still in print and her Alliance for God Cognizance (Ludendorff) still exists and is monitored by the National Intelligence Agency.

Eduard Gamper (1887-1938): cases and accidents.

Eduard Gamper (1887-1938) was Head of the Department of Neuropsychiatry at the Charles University's German Faculty of Medicine in Prague. He had trained in Innsbruck, where he undertook groundbreaking work on the midbrain in an anencephalic child and in a series of patients who had died from Wernicke's encephalopathy. Gamper identified the mamillary bodies as key in the performance of declarative memory. Considered an expert in memory disorders, he was chosen by the Medical Faculty in Innsbruck to provide expert opinion on the notorious case of Philipp Halsmann, who was suspected of murdering his father. Details of the case remained unresolved and Gamper's opinion caused both professional and political controversy. When in Prague, Gamper made great efforts to improve patient care and clinical services, establishing a special ward for patients with neurological conditions. This task was not nearly completed, when he and his wife died after their car drove over a cliff into the Walchensee in Bavaria. Rumours surrounded his death: that Gamper had just examined Adolf Hitler; that he was a political victim; that the Gestapo were behind the accident. After an investigation of the available evidence, we can report that an unusual 22 cm of snow fell in the area of the Walchensee on April 20, 1938, the day of the Gampers' deaths. We were unable to find any evidence for foul play in what appears to have been a tragic accident.

[Excited Delirium Syndrome (ExDS): emergence and emergency management]. / Erregungssturm ­ Entstehung und Notfallbehandlung.

The Excited Delirium Syndrome (ExDS) is a state of maximum psychophysiological excitation far beyond mental agitation. Patients themselves are at an acute risk and put others at a high risk. We present data from eleven patients and a short literature review. Results: 9 of 11 patients were acutely intoxicated (alcohol, magic mushrooms, THC, ecstacy, or "flakka"). Eight had a history of substance abuse and 4 of other mental illness. None of the patients responded to attempts at verbal de-escalation. Seven had significant injuries at the time of admission to the hospital. The aggressive "psychiatric" presentation of ExDS can lead to vital risks being overlooked (hyperexcitation, acidosis, rhabdomyolysis, hypoxemia, and cardiovascular decompensation), which may even be increased by severe methods of restraint (hogtie; positional asphyxia). Early recognition of ExDS and its risks, comprehensive management and the prevention of inappropriate treatment will help to reduce fatal outcomes.

[The "Fourth Wave"? COVID-19 and consecutive cognitive impairment]. / Die "vierte Welle"? COVID-19 und konsekutive kognitive Störungen.

The COVID-19 pandemic poses new challenges for the healthcare systems world-wide which will go beyond prevention, acute and intensive care treatment of patients with severe illness. A large proportion of "COVID-survivors" - and not only elderly patients - suffers from "post-COVID-syndrome". Risk factors are preexisting somatic multimorbidity, cognitive and cerebral changes together with pneumonia and hypoxemia, intensive care treatment and confusional states during the acute phase of illness. Post-COVID cognitive deficits usually manifest as a frontal dysexecutive syndrome combined with fatigue and dysphoria and/or with attentional and memory deficits. Several pathogenetic mechanisms of COVID encephalopathy are understood, but no specific treatment strategies have been established so far. We assume that general practitioners, psychiatrists, neurologists and social workers will need to take care of the activation, reintegration and expert appraisals of patients with post-COVID fatigue and cognitive deficits during the years to come.

[Old and depressed and/or demented? - Pseudodepression vs. pseudodementia]. / Alt und depressiv oder dement? ­ Pseudodepression vs. Pseudodemenz.

Many elderly patients suffer from both, depressive symptoms and cognitive deficits. Clinically, it oftentimes appears unclear whether the affective or the cognitive problems are primary or secondary. Modern molecular and imaging markers contribute to a more efficient distinction between depression and incipient dementia due to neurodegenerative, vascular, and other diseases. A careful history and clinical investigations are necessary to identify the underlying diseases, but they do not always offer sufficient therapeutic guidance. If in doubt, the condition should always be considered as potentially reversible and treated emphatically (but with age-appropriate caution).

[Catatonic walks with Emil Kraepelin, Aloys Alzheimer, Henry Aloysius Cotton and others]. / Katatones Wandern mit Emil Kraepelin, Aloys Alzheimer, Henry Aloysius Cotton und anderen.

Staff outings of Emil Kraepelin's Royal Department of Psychiatry were known as "catatonic walks". A remarkable number of important German and international visitors participated in 1906, Nicolas Achucarro, Henry Cotton, Eduard Flatau, Smith Ely Jelliffe, Gaetano Perusini, Edward Scripture, Maurycy Urstein and others. Many of Kraepelin's collaborators were inspired by his ideas and driven by scientific enthusiasm which contributed to significant scientific advances, but also took them to very different ends from dental and bowel surgery to psychoanalysis and eventually evidence-based medicine; from racial hygiene and nationalism to the presidency of communist Romania.

[The COVID - Conspiracy: Theory and Practice]. / Die COVID-19-Verschwörung in Theorie und Praxis.

Conspiracy theories are a most elaborate form of gossip. They have a long tradition and arise preferably during times of drawn out crises, as for example the Corona-pandemic. Hard-wired anxiety, personal powerlessness, palpable socioeconomic consequences, complex causes and insufficient solutions, disconcerting leadership and modern means of communication form fertile ground for conspiracy theories. They are much more than a peculiar marginal phenomenon as they undermine concerted action and distort open discussions, spreading germs and doubts, increasing risks and costs. This paper describes individual, social and communicative mechanisms underlying conspiracy theories and their inclusive ("we, who know"), conclusive (cognitive closure versus inconclusive facts) and exclusive effects ("we versus the establishment and the ignorants").

Regional Cerebral Associations Between Psychometric Tests and Imaging Biomarkers in Alzheimer's Disease.

Recently, imaging biomarkers have gained importance for the characterization of patients with Alzheimer's disease; however, the relationship between regional biomarker expression and cognitive function remains unclear. In our study, we investigated associations between scores on CERAD neuropsychological assessment battery (CERAD-NAB) subtests with regional glucose metabolism, cortical thickness and amyloid deposition in patients with early Alzheimer's disease (AD) using [18F]-fluorodeoxyglucose (FDG), structural MRI, and 11C-Pittsburgh Compound B (PiB) positron emission tomography (PET), respectively. A total of 76 patients (mean age 68.4 ± 8.5 years, 57.9% male) with early AD (median global clinical dementia rating (CDR) score = 0.5, range: 0.5-2.0) were studied. Associations were investigated by correlation and multiple regression analyses. Scores on cognitive subtests were most closely predicted by regional glucose metabolism with explained variance up to a corrected R² of 0.518, followed by cortical thickness and amyloid deposition. Prediction of cognitive subtest performance was increased up to a corrected R² of 0.622 for Word List-Delayed Recall, when biomarker information from multiple regions and multiple modalities were included. For verbal, visuoconstructive and mnestic domains the closest associations with FDG-PET imaging were found in the left lateral temporal lobe, right parietal lobe, and posterior cingulate cortex, respectively. Decreased cortical thickness in parietal regions was most predictive of impaired subtest performance. Remarkably, cerebral amyloid deposition significantly predicted cognitive function in about half of the subtests but with smaller extent of variance explained (corrected R² ≤ 0.220). We conclude that brain metabolism and atrophy affect cognitive performance in a regionally distinct way. Significant predictions of cognitive function by PiB-PET in half of CERAD-NAB subtests suggest functional relevance even in symptomatic patients with AD, challenging the concept of plateauing cortical amyloid deposition early in the disease course. Our results underscore the complex spatial relationship between different imaging biomarkers.

Therapeutic Drug Monitoring of Rivastigmine and Donepezil Under Consideration of CYP2D6 Genotype-Dependent Metabolism of Donepezil.

BACKGROUND: The efficacy of acetylcholinesterase inhibitors (AChE-I) might depend on blood concentration. While rivastigmine metabolism is independent of the cytochrome P450 system, its isoenzymes, especially CYP2D6, metabolize donepezil. CYP2D6 polymorphisms can cause altered enzyme activity resulting in lower or higher than expected drug concentrations of donepezil. OBJECTIVE: We investigated correlations between clinical efficacy and serum concentrations of rivastigmine and donepezil under special consideration of CYP 2D6 genotype or gene dose-dependent metabolism of donepezil. METHODS: Serum concentrations of donepezil and rivastigmine were measured by liquid chromatography - tandem mass spectrometry (LC-MS/MS). Real-time quantitative polymerase chain reaction (PCR) and allele-specific PCR were performed to assess CYP2D6 genotype and gene dose. RESULTS: Patients treated with rivastigmine (n=28) or donepezil (n=48) were included in the study. Both gene dose and metabolism type significantly predicted the level of donepezil serum concentration (p=0.019 and p=0.013, respectively). In the rivastigmine group, changes of the word list delayed recall subtest before treatment and under stable medication were significantly associated with rivastigmine serum levels (ß=0.465; p=0.018). Drug serum concentrations were outside the recommended range in a substantial percentage of participants, which might have contributed to poor correlations between changes in cognitive measures and drug concentrations. Donepezil serum concentrations significantly depended on CYP2D6 gene dose. CONCLUSION: Testing AChE-I serum concentration should be considered in patients without clinical response to treatment or those with severe side effects. Patients with donepezil drug levels outside the recommended range might additionally profit from CYP2D6 genotyping or treatment with an AChE-I independent of CYP metabolism.

Aging Heads of State: The Politics of Dementia and Geriatric Cognitive Disorders.

BACKGROUND: Increasing life expectancy may explain why more elderly candidates appear to be running for office. This raises general questions regarding the specific risks of old age and frailty in demanding political positions. Therefore, I tried to give important contemporary examples of elderly leaders, study the mean age of leading political figures over the last 3 decades and present historical examples of heads of state with age-associated brain diseases and cognitive deficits. I reviewed the literature on mental illness and politics and analyzed the ages of international political leaders in 1990, 2000, 2010 and 2020. SUMMARY: There are several impressive contemporary examples of elderly politicians. The mean age of political leaders has not increased significantly in most parts of the world over the last 3 decades with the exception of the Gulf States and sub-Saharan Africa. Health problems of heads of state in earlier centuries had not been primarily age associated. After 1900, dementia but also mild cognitive and mild behavioral impairment became important issues in politically critical situations, for example international peace negotiations, the rise of Nazi Germany, the breakup of communism, the Arab Spring and others. Key Messages: This paper collects anecdotal evidence of cognitive frailty in ageing politicians; it is not an in-depth analysis of political history. Observations confirm that a very long time in power may obviously increase the risk of age-associated problems; dynamic revolutionary or entrepreneurial idols may be misled to rely on their irreplaceable charisma for too long. However, caution must be exercised against ageism on one side versus silent acquiescence towards leaders with failing mental powers on the other, who may become victims of obscure parties and their decompensating personality disorders.