White matter hyperintensity patterns: associations with comorbidities, amyloid, and cognition.

BACKGROUND: White matter hyperintensities (WMHs) are often measured globally, but spatial patterns of WMHs could underlie different risk factors and neuropathological and clinical correlates. We investigated the spatial heterogeneity of WMHs and their association with comorbidities, Alzheimer's disease (AD) risk factors, and cognition. METHODS: In this cross-sectional study, we studied 171 cognitively unimpaired (CU; median age: 65 years, range: 50 to 89) and 51 mildly cognitively impaired (MCI; median age: 72, range: 53 to 89) individuals with available amyloid (18F-flutementamol) PET and FLAIR-weighted images. Comorbidities were assessed using the Cumulative Illness Rating Scale (CIRS). Each participant's white matter was segmented into 38 parcels, and WMH volume was calculated in each parcel. Correlated principal component analysis was applied to the parceled WMH data to determine patterns of WMH covariation. Adjusted and unadjusted linear regression models were used to investigate associations of component scores with comorbidities and AD-related factors. Using multiple linear regression, we tested whether WMH component scores predicted cognitive performance. RESULTS: Principal component analysis identified four WMH components that broadly describe FLAIR signal hyperintensities in posterior, periventricular, and deep white matter regions, as well as basal ganglia and thalamic structures. In CU individuals, hypertension was associated with all patterns except the periventricular component. MCI individuals showed more diverse associations. The posterior and deep components were associated with renal disorders, the periventricular component was associated with increased amyloid, and the subcortical gray matter structures was associated with sleep disorders, endocrine/metabolic disorders, and increased amyloid. In the combined sample (CU + MCI), the main effects of WMH components were not associated with cognition but predicted poorer episodic memory performance in the presence of increased amyloid. No interaction between hypertension and the number of comorbidities on component scores was observed. CONCLUSION: Our study underscores the significance of understanding the regional distribution patterns of WMHs and the valuable insights that risk factors can offer regarding their underlying causes. Moreover, patterns of hyperintensities in periventricular regions and deep gray matter structures may have more pronounced cognitive implications, especially when amyloid pathology is also present.

Explaining variability in early stages of [18F]-flortaucipir tau-PET binding: Focus on sex differences.

INTRODUCTION: Female sex is associated with increased [18F]-flortaucipir signal, which may be affected by amyloid pathology, age, and off-target binding in skull and meninges. METHODS: In this cross-sectional study comprising 52 females and 52 matched males, we examined sex-related differences in regional tau-positron emission tomography (PET) with and without considering off-target binding. We assessed the respective contributions of sex, age, amyloid-PET burden, and off-target binding to tau-PET signal. We explored associations between age at menopause and hormone replacement therapy (HRT) use with regional tau-PET signals. RESULTS: Female sex was associated with increased regional tau both independently and interactively with amyloid, but amyloid-independent associations were largely reduced when controlling for off-target binding. Age but not age*sex interactions explained a small but significant amount of tau-PET signal in temporoparietal regions. Considering the sample size and limited range of amyloid-PET burden, no clear associations between regional tau-PET signals and age at menopause or HRT use could be found. DISCUSSION: Female sex is associated with increased [18F]-flortaucipir signal mainly through its interaction with amyloid.

Frequency and predictors of headache in the first 12 months after traumatic brain injury: results from CENTER-TBI.

BACKGROUND: Headache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury. METHODS: A large patient sample from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study was used. Patients were stratified based on their clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU) in the acute phase. Headache was assessed using a single item from the Rivermead Post-Concussion Symptoms Questionnaire measured at baseline, 3, 6 and 12 months after injury. Mixed-effect logistic regression analyses were applied to investigate changes in headache frequency and associated predictors. RESULTS: A total of 2,291 patients responded to the headache item at baseline. At study enrolment, 59.3% of patients reported acute headache, with similar frequencies across all strata. Female patients and those aged up to 40 years reported a higher frequency of headache at baseline compared to males and older adults. The frequency of severe headache was highest in patients admitted to the ICU. The frequency of headache in the ER stratum decreased substantially from baseline to 3 months and remained from 3 to 6 months. Similar trajectory trends were observed in the ICU and ADM strata across 12 months. Younger age, more severe TBI, fatigue, neck pain and vision problems were among the predictors of more severe headache over time. More than 25% of patients experienced headache at 12 months after injury. CONCLUSIONS: Headache is a common symptom after TBI, especially in female and younger patients. It typically decreases in the first 3 months before stabilising. However, more than a quarter of patients still experienced headache at 12 months after injury. Translational research is needed to advance the clinical decision-making process and improve targeted medical treatment for headache. TRIAL REGISTRATION: ClinicalTrials.gov NCT02210221.

Traumatic Encephalopathy Syndrome and Tauopathy in a 19-Year-Old With Child Abuse.

The majority of traumatic encephalopathy syndrome (TES) cases have been reported in former contact sport athletes. This is the first case with TES in a 19-year-old male patient with progressive cognitive decline after daily domestic physical violence through repeated hits to the head for 15 years. The patient presented with a moderate depressive episode and progressive cognitive decline. Tau positron emission tomography (PET) with 220 MBq of [18F]PI-2620 revealed increased focal signal at the frontal and parietal white/gray matter border. Brain magnetic resonance imaging (MRI) showed a cavum septum pellucidum, reduced left-sided hippocampal volume, and a left midbrain lesion. Cerebrospinal fluid results showed elevated total and p-tau. Neurocognitive testing at admission showed memory deficits clearly below average, and hampered dysfunctions according to the slow processing speed with a low mistake rate, indicating the acquired, thus secondary, attentional deficits. We diagnosed the patient with a TES suggestive of chronic traumatic encephalopathy and classified him as having subtle/mild functional limitation with a most likely transition to mild dementia within the TES criteria. This report underlines child abuse as a relevant criterion in diagnosing TES in cases with repetitive hits to the head. In addition to clinical markers, we show the relevance of fluid tau biomarkers and tau-PET to support the diagnosis of TES according to the recently published diagnosis criteria for TES.

Age-, sex-, and pathology-related variability in brain structure and cognition.

This work aimed to investigate potential pathways linking age and imaging measures to early age- and pathology-related changes in cognition. We used [18F]-Flutemetamol (amyloid) and [18F]-Flortaucipir (tau) positron emission tomography (PET), structural MRI, and neuropsychological assessment from 232 elderly individuals aged 50-89 years (46.1% women, 23% APOE-ε4 carrier, 23.3% MCI). Tau-PET was available for a subsample of 93 individuals. Structural equation models were used to evaluate cross-sectional pathways between age, amyloid and tau burden, grey matter thickness and volumes, white matter hyperintensity volume, lateral ventricle volume, and cognition. Our results show that age is associated with worse outcomes in most of the measures examined and had similar negative effects on episodic memory and executive functions. While increased lateral ventricle volume was consistently associated with executive function dysfunction, participants with mild cognitive impairment drove associations between structural measures and episodic memory. Both age and amyloid-PET could be associated with medial temporal lobe tau, depending on whether we used a continuous or a dichotomous amyloid variable. Tau burden in entorhinal cortex was related to worse episodic memory in individuals with increased amyloid burden (Centiloid >12) independently of medial temporal lobe atrophy. Testing models for sex differences revealed that amyloid burden was more strongly associated with regional atrophy in women compared with men. These associations were likely mediated by higher tau burden in women. These results indicate that influences of pathological pathways on cognition and sex-specific vulnerabilities are dissociable already in early stages of neuropathology and cognitive impairment.

Sensitivity of outcome instruments in a priori selected patient groups after traumatic brain injury: Results from the CENTER-TBI study.

Traumatic brain injury (TBI) can negatively impact patients' lives on many dimensions. Multiple instruments are available for evaluating TBI outcomes, but it is still unclear which instruments are the most sensitive for that purpose. This study examines the sensitivity of nine outcome instruments in terms of their ability to discriminate within and between specific patient groups, selected a priori as identified from the literature, at three different time points within a year after TBI (i.e., 3, 6, and 12 months post injury). The sensitivity of the instruments to sociodemographic (sex, age, education), premorbid (psychological health status), and injury-related (clinical care pathways, TBI and extracranial injury severity) factors was assessed by means of cross-sectional multivariate Wei-Lachin analyses. The Glasgow Outcome Scale Extended (GOSE)-the standard in the field of TBI for measuring functional recovery-demonstrated the highest sensitivity in most group comparisons. However, as single functional scale, it may not be able to reflect the multidimensional nature of the outcome. Therefore, the GOSE was used as a reference for further sensitivity analyses on more specific outcome scales, addressing further potential deficits following TBI. The physical component summary score (PCS) of the generic health-related quality of life (HRQOL) instruments (SF-36v2/-12v2) and the TBI-specific HRQOL instruments (QOLIBRI/-OS) were most sensitive in distinguishing recovery after TBI across all time points and patient groups, followed by the RPQ assessing post-concussion symptoms and the PHQ-9 measuring depression. The SF-36v2/-12v2 mental component summary score and the GAD-7 measuring anxiety were less sensitive in several group comparisons. The assessment of the functional recovery status combined with generic HRQOL (the PCS of the SF-12v2), disease-specific HRQOL (QOLIBRI-OS), and post-concussion symptoms (RPQ) can provide a sensitive, comprehensive, yet time-efficient evaluation of the health status of individuals after TBI in different patient groups.

Relationship Between Time of Admission, Help-Seeking Behavior, and Psychiatric Outcomes: "From Dusk Till Dawn".

Introduction: Day and time of admission influence treatment outcomes and prognosis in several medical specialties; this seems related to resources' ability. It is largely unknown whether this also applies to mental health services. We investigate the relationship between time of admission, patients' demographic and clinical profile, and treatment outcomes. Methods: Demographic and clinical profiles of admitted and discharged patients to a general psychiatric ward between January 1st, 2013 and December 31st, 2020, were analyzed. In addition, we used the last year (i.e., 2020) to monitor rehospitalization. Time of admission was defined as weekdays (working day, weekend) and dayshifts (daytime, dusk, and dawn). Results: During the study period, 12,449 patient admissions occurred. The mean age of the sample was 48.05 ± 20.90 years, with 49.32% (n = 6,140) females. Most admissions (n = 10,542, 84%) occurred on working days. Two-fifths of admissions (39.7%, n = 4,950) were compulsory, with a higher rate outside daytime hours. Patients had slight differences in the clinical profile, resulting from evaluating the different items of the Health of Nation Outcome Scale (HoNOS). Patients admitted on night shifts, weekends, and holidays showed a shorter length of stay; patients compulsorily admitted during daytime (disregarding the day of the week) had a longer length of stay. All patient groups achieved a robust clinical improvement (i.e., an HoNOS score reduction of around 50%), with similar readmission rates. Discussion: The main finding of our study is the relationship between "daytime hours" and fewer compulsory admissions, a result of the interplay between demographics, clinical characteristics, and out-of-clinic service availability (such as ambulatory psychiatric- psychological praxis; day-clinic; home-treatment). The differing clinical profile, in turn, determines differences in treatment selection, with patients admitted after office hours experiencing a higher rate of coercive measures. The shorter length of stay for out-of-office admissions might result from the hospitalization as an intervention. These results should encourage the implementation of outpatient crisis-intervention services, available from dusk till dawn.

Lifestyle Affects Amyloid Burden and Cognition Differently in Men and Women.

OBJECTIVE: Evidence on associations of lifestyle factors with Alzheimer's pathology and cognition are ambiguous, potentially because they rarely addressed inter-relationships of factors and sex effects. While considering these aspects, we examined the relationships of lifestyle factors with brain amyloid burden and cognition. METHODS: We studied 178 cognitively normal individuals (women, 49%; 65.0 [7.6] years) and 54 individuals with mild cognitive impairment (women, 35%; 71.3 [8.3] years) enrolled in a prospective study of volunteers who completed 18 F-Flutemetamol amyloid positron emission tomography. Using structural equation modeling, we examined associations between latent constructs representing metabolic/vascular risk, physical activity, and cognitive activity with global amyloid burden and cognitive performance. Furthermore, we investigated the influence of sex in this model. RESULTS: Overall, higher cognitive activity was associated with better cognitive performance and higher physical activity was associated with lower amyloid burden. The latter association was weakened to a nonsignificant level after excluding multivariate outliers. Examination of the moderating effect of sex in the model revealed an inverse association of metabolic/vascular risk with cognition in men, whereas in women metabolic/vascular risk trended toward increased amyloid burden. Furthermore, a significant inverse association between physical activity and amyloid burden was found only in men. Inheritance of an APOE4 allele was associated with higher amyloid burden only in women. INTERPRETATION: Sex modifies effects of certain lifestyle-related factors on amyloid burden and cognition. Notably, our results suggest that the negative impact of metabolic/vascular risk influences the risk of cognitive decline and Alzheimer's disease through distinct paths in women and men. ANN NEUROL 2022;92:451-463.

Heart-brain interactions in cardiac and brain diseases: why sex matters.

Cardiovascular disease and brain disorders, such as depression and cognitive dysfunction, are highly prevalent conditions and are among the leading causes limiting patient's quality of life. A growing body of evidence has shown an intimate crosstalk between the heart and the brain, resulting from a complex network of several physiological and neurohumoral circuits. From a pathophysiological perspective, both organs share common risk factors, such as hypertension, diabetes, smoking or dyslipidaemia, and are similarly affected by systemic inflammation, atherosclerosis, and dysfunction of the neuroendocrine system. In addition, there is an increasing awareness that physiological interactions between the two organs play important roles in potentiating disease and that sex- and gender-related differences modify those interactions between the heart and the brain over the entire lifespan. The present review summarizes contemporary evidence of the effect of sex on heart-brain interactions and how these influence pathogenesis, clinical manifestation, and treatment responses of specific heart and brain diseases.

Influence of footwear on postural sway: A systematic review and meta-analysis on barefoot and shod bipedal static posturography in patients and healthy subjects.

BACKGROUND: Bipedal static posturography is widely used to assess postural control. However, standardized methods and evidence on the influence of footwear on balance in comparison to barefoot stance is sparse. RESEARCH QUESTIONS: Is bipedal static posturography applied in a standardized way with respect to demographics and the experimental set-up (systematic review)? Does habitual footwear influence postural control in comparison to barefoot condition during bipedal static posturography in adult patients and healthy subjects (meta-analysis)? METHODS: For this systematic review and meta-analysis, a comprehensive follow-up literature search was conducted from March 2009 until January 2020 according to the PRISMA guidelines. Original, research articles reporting on bipedal, unsupported, static posturography in adults (≥18 years) were included according to inclusion criteria (age, sex, height, weight, duration, repetitions, visual/foot condition, sampling frequency). Studies comparing habitual footwear with barefoot condition during bipedal static posturography were included for the meta-analysis. Center of pressure parameters (sway velocity, range, root mean square, paths lengths) with subjects having eyes closed (EC) or open (EO) were analyzed using random effects models. RESULTS: For this systematic review and meta-analysis, 207 and eight out of 5189 studies with 12'341 and 156 subjects, respectively, were eligible. Most studies (89%) reported barefoot, 5% shod, and 6% barefoot and shod measurements. Less than half of studies (44%) included patients of which the minority (13%) suffered from neurological disease. Sway velocity in the anterior-posterior direction was higher in habitual shoes compared to barefoot with EC (SMD: 1.08; 95% CI: 0.68-1.48; p < 0.01; I2 = 0%), with EO (SMD: 0.68; 95% CI: 0.11-1.26; p = 0.02; I2 = 1%), and in the medio-lateral direction with EC (SMD: 1.30; 95% CI: 0.76-1.85, p < 0.01; I2 = 37%). SIGNIFICANCE: Methodical heterogeneity of bipedal static posturography hampers studies' comparability. Thus, we provide a standardized approach to increase knowledge whether habitual footwear decrease postural control in comparison to barefoot stance.

Longitudinal Analyses of the Reciprocity of Depression and Anxiety after Traumatic Brain Injury and Its Clinical Implications.

Depression and anxiety are common following traumatic brain injury (TBI). Understanding their prevalence and interplay within the first year after TBI with differing severities may improve patients' outcomes after TBI. Individuals with a clinical diagnosis of TBI recruited for the large European collaborative longitudinal study CENTER-TBI were screened for patient-reported major depression (MD) and generalized anxiety disorder (GAD) at three, six, and twelve months post-injury (N = 1683). Data were analyzed using autoregressive cross-lagged models. Sociodemographic, premorbid and injury-related factors were examined as risk factors. 14.1-15.5% of TBI patients reported moderate to severe MD at three to twelve months after TBI, 7.9-9.5% reported GAD. Depression and anxiety after TBI presented high within-domain persistency and cross-domain concurrent associations. MD at three months post-TBI had a significant impact on GAD at six months post-TBI, while both acted bidirectionally at six to twelve months post-TBI. Being more severely disabled, having experienced major extracranial injuries, an intensive care unit stay, and being female were risk factors for more severe MD and GAD. Major trauma and the level of consciousness after TBI were additionally associated with more severe MD, whereas being younger was related to more severe GAD. Individuals after TBI should be screened and treated for MD and GAD early on, as both psychiatric disturbances are highly persistent and bi-directional in their impact. More severely disabled patients are particularly vulnerable, and thus warrant timely screening and intensive follow-up treatment.

[Recommendations for the Diagnosis and Therapy of Psychotic Disorders in the Elderly]. / Empfehlungen für die Diagnostik und Therapie psychotischer Erkrankungen im Alter.

Recommendations for the Diagnosis and Therapy of Psychotic Disorders in the Elderly Abstract. Psychotic disorders in the elderly cover a wide range of causes and manifestations. They often occur as part of a depression, dementia, substance abuse or delirium. While psychosis can occur with a first manifestation in advanced age, many patients with chronic psychotic disorders reach a high age. Many elderly individuals are also affected by cognitive impairment and somatic conditions, making a third-party history most relevant. The associated changes in life and the complexity of the individual situation needs to be integrated into the diagnosis and treatment. The presented recommendations have been developed under the lead of the Swiss Society of Old Age Psychiatry (SGAP) in collaboration with the Swiss Association of Nurses (SBK) and the subcommittees for gerontological and psychiatric nursing of the association of nursing science (VFP) as well as further professional societies. We aim to make current knowledge concerning diagnosis and treatment available to the interprofessional teams working in in- and outpatients' settings.

Reference Values and Psychometric Properties of the Quality of Life After Traumatic Brain Injury-Overall Scale in Italy, The Netherlands, and the United Kingdom.

OBJECTIVES: The Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS) is a short screening instrument for assessing disease-specific health-related quality of life (HRQoL) after traumatic brain injury. To date, no reference values are available for the QOLIBRI-OS in general populations. Thus, this study aimed to establish reference values for the QOLIBRI-OS in general population samples from Italy, The Netherlands, and the United Kingdom. METHODS: Data were collected using an online survey. The total sample comprised 11759 participants, consisting of 3549 Italian, 3564 Dutch, and 4646 British subjects. In this sample, 49% of the total sample did not report any health complaints, whereas 51% had at least 1 chronic health condition. Reference values were deduced for the QOLIBRI-OS for health-condition-related samples and total general population samples per country. To ensure the comparability of these values, measurement invariance was assessed using a multigroup confirmatory factor analysis. Covariates characterizing the reference values were selected with the help of regression analyses. RESULTS: The confirmatory factor analysis confirmed that the QOLIBRI-OS scores measured the same traumatic brain injury-specific HRQoL construct across the 3 countries. Healthy individuals reported significantly higher HRQoL than individuals with at least 1 chronic health condition. Older age and higher education levels were significantly associated with higher HRQoL. CONCLUSIONS: Because the reference values displayed differences in terms of age and education level across the 3 countries, we recommend using country-specific reference values stratified by sociodemographic and health status in research and clinical practice.

Translation and Linguistic Validation of Outcome Instruments for Traumatic Brain Injury Research and Clinical Practice: A Step-by-Step Approach within the Observational CENTER-TBI Study.

Assessing outcomes in multinational studies on traumatic brain injury (TBI) poses major challenges and requires relevant instruments in languages other than English. Of the 19 outcome instruments selected for use in the observational Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, 17 measures lacked translations in at least one target language. To fill this gap, we aimed to develop well-translated linguistically and psychometrically validated instruments. We performed translations and linguistic validations of patient-reported measures (PROMs), clinician-reported (ClinRO), and performance-based (PerfO) outcome instruments, using forward and backward translations, reconciliations, cognitive debriefings with up to 10 participants, iterative revisions, and international harmonization with input from over 150 international collaborators. In total, 237 translations and 211 linguistic validations were carried out in up to 20 languages. Translations were evaluated at the linguistic and cultural level by coding changes when the original versions are compared with subsequent translation steps, using the output of cognitive debriefings, and using comprehension rates. The average comprehension rate per instrument varied from 88% to 98%, indicating a good quality of the translations. These outcome instruments provide a solid basis for future TBI research and clinical practice and allow the aggregation and analysis of data across different countries and languages.

Psychopathological Symptom Load and Distinguishable Cerebral Blood Flow Velocity Patterns in Patients With Schizophrenia and Healthy Controls: A Functional Transcranial Doppler Study.

Introduction: Schizophrenia is a severe psychiatric disorder, with executive dysfunction and impaired processing speed playing a pivotal role in the course of the disease. In patients with schizophrenia, neurocognitive deficits appear to be related to alterations in cerebral hemodynamics. It is not fully understood if psychopathological symptom load (i.e., presence and severity of symptoms) is also related to alterations in cerebral hemodynamics. We aim to study the relationship between psychopathological symptom load and cerebral hemodynamics in the Middle Cerebral Artery (MCA) during a cognitive task in patients with schizophrenia and healthy controls. Methodology: Cerebral hemodynamics in the MCA were examined in 30 patients with schizophrenia and 15 healthy controls using functional Transcranial Doppler (fTCD) during the Trail Making Test (TMT). Psychopathological symptoms were measured using the Brief Psychiatric Rating Scale (BPRS). Patients were dichotomized according to BPRS scores: mild-moderate (BPRS < 41, n = 15) or marked-severe (BPRS ≧ 41, n = 15). Mean blood flow velocity (MFV) in the MCA and processing speed of the TMT were analyzed. Cerebral hemodynamics were analyzed using the general additional model (GAM) with a covariate analysis of variance (ANCOVA) for group comparisons. Results: Patients and healthy controls were comparable regarding demographics. Patients had a slower processing speed for the TMT-A (patients-severe: 52s, patients-moderate: 40s, healthy-controls: 32s, p = 0.019) and TMT-B [patients-severe: 111s, patients-moderate: 76s, healthy-controls: 66s, p < 0.001)]. Patients demonstrated differing hemodynamic profiles in both TMTs: TMT- A [F (6, 1,792) = 17, p < 0.000); TMT-B [F (6, 2,692) = 61.93, p < 0.000], with a delay in increase in MFV and a failure to return to baseline values. Conclusions: Patients with schizophrenia demonstrated slower speeds of processing during both the TMT-A and TMT-B. The speed of processing deteriorated with increasing psychopathological symptom load, additionally a distinct cerebral hemodynamic pattern in the MCA was observed. Our results further support the view that severity of schizophrenia, particularly psychopathological symptom load, influences performance in neurocognitive tasks and is related to distinct patterns of brain hemodynamics.

Psychometric Characteristics of the Patient-Reported Outcome Measures Applied in the CENTER-TBI Study.

Traumatic brain injury (TBI) may lead to impairments in various outcome domains. Since most instruments assessing these are only available in a limited number of languages, psychometrically validated translations are important for research and clinical practice. Thus, our aim was to investigate the psychometric properties of the patient-reported outcome measures (PROM) applied in the CENTER-TBI study. The study sample comprised individuals who filled in the six-months assessments (GAD-7, PHQ-9, PCL-5, RPQ, QOLIBRI/-OS, SF-36v2/-12v2). Classical psychometric characteristics were investigated and compared with those of the original English versions. The reliability was satisfactory to excellent; the instruments were comparable to each other and to the original versions. Validity analyses demonstrated medium to high correlations with well-established measures. The original factor structure was replicated by all the translations, except for the RPQ, SF-36v2/-12v2 and some language samples for the PCL-5, most probably due to the factor structure of the original instruments. The translation of one to two items of the PHQ-9, RPQ, PCL-5, and QOLIBRI in three languages could be improved in the future to enhance scoring and application at the individual level. Researchers and clinicians now have access to reliable and valid instruments to improve outcome assessment after TBI in national and international health care.

Interfering with fear memories by eye movement desensitization and reprocessing.

OBJECTIVE: Pharmacologic and behavioral interventions that block reconsolidation of reactivated fear memory have demonstrated only limited success in modifying stronger and long-standing fear memories. Given the efficacy of Eye Movement Desensitization and Reprocessing (EMDR) in treating PTSD, pursuit eye movements are a promising and novel intervention for studies of human memory reconsolidation. Here, we examined the efficacy of pursuit eye movements in interfering with reconsolidation of conditioned fear memories. METHODS: We conducted a 3-day differential Pavlovian fear conditioning procedure in healthy adults, using videos of biologically prepared stimuli (tarantulas), partly reinforced with electrical shocks while recording skin conductance response (SCR) as a measure of autonomic conditioned responses. Fear conditioning was performed on Day 1. On Day 2, 38 participants were randomized into groups performing pursuit eye movements either immediately after fear memory reactivation, when the fear memory was stable, or 10 min later, when the fear memory was assumed to be more labile. On Day 3, fear memory strength was assessed by SCR to both reactivated and nonreactivated fear memories. RESULTS: Strong differential conditioning to the spider stimuli were observed during both fear acquisition and fear memory reactivation. Reactivated fear memory conditioned responses of participants performing pursuit eye movements after a 10-min delay were significantly smaller in the reinstatement phase (0.16 µS; 95% CI [0.02, 0.31]). CONCLUSIONS: Pursuit eye movements were effective in reducing fear-conditioned SCR in reinstatement. This result supports the theoretical proposition that EMDR can interfere with reactivated fear memory reconsolidation.

[Consequences of the COVID-19 pandemic for people with schizophrenia, dementia and substance use disorders]. / Folgen der COVID-19-Pandemie für Menschen mit Schizophrenie, Demenz und Abhängigkeitserkrankungen.

The coronavirus disease 2019 (COVID-19) pandemic poses unexpected challenges to social and healthcare systems worldwide. The direct and indirect medical consequences of infection with the novel coronavirus bring healthcare systems to their limits of their capabilities in many places. The neurotropic effects of COVID-19 can result not only in neurological but also in acute and long-term psychological sequelae. In the psychiatric context, the psychological and psychosocial consequences of contact restrictions and lockdowns as well as the effects of daily reports in the media on people with mental disorders must also be taken into consideration. In this article the consequences of the COVID-19 pandemic for people with mental illnesses, especially those with schizophrenia, dementia, and addictive diseases are discussed.

Persistent postconcussive symptoms in children and adolescents with mild traumatic brain injury receiving initial head computed tomography.

OBJECTIVE: The aim of this paper was to evaluate the prevalence of postconcussive symptoms and their relation to health-related quality of life (HRQOL) in pediatric and adolescent patients with mild traumatic brain injury (mTBI) who received head CT imaging during initial assessment. METHODS: Patients aged between 5 and 21 years with mTBI (Glasgow Coma Scale scores 13-15) and available Rivermead Post Concussion Questionnaire (RPQ) at 6 months of follow-up in the multicenter, prospectively collected CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) study were included. The prevalence of postconcussive symptoms was assessed, and the occurrence of postconcussive syndrome (PSC) based on the ICD-10 criteria, was analyzed. HRQOL was compared in patients with and without PCS using the Quality of Life after Brain Injury (QOLIBRI) questionnaire. RESULTS: A total of 196 adolescent or pediatric mTBI patients requiring head CT imaging were included. High-energy trauma was prevalent in more than half of cases (54%), abnormalities on head CT scans were detected in 41%, and admission to the regular ward or intensive care unit was necessary in 78%. Six months postinjury, 36% of included patients had experienced at least one moderate or severe symptom on the RPQ. PCS was present in 13% of adolescents and children when considering symptoms of at least moderate severity, and those patients had significantly lower QOLIBRI total scores, indicating lower HRQOL, compared with young patients without PCS (57 vs 83 points, p < 0.001). CONCLUSIONS: Adolescent and pediatric mTBI patients requiring head CT imaging show signs of increased trauma severity. Postconcussive symptoms are present in up to one-third of those patients, and PCS can be diagnosed in 13% 6 months after injury. Moreover, PCS is significantly associated with decreased HRQOL.

Quality of life after traumatic brain injury: a cross-sectional analysis uncovers age- and sex-related differences over the adult life span.

Traumatic brain injury (TBI) is the leading cause of disability in the working population and becomes increasingly prevalent in the elderly. Thus, TBI is a major global health burden. However, age- and sex-related long-term outcome regarding patient's health-related quality of life (HRQoL) is yet not clarified. In this cross-sectional study, we present age- and sex-related demographics and HRQoL up to 10 years after TBI using the Quality of Life after Brain Injury (QOLIBRI) instrument. The QOLIBRI total score ranges from zero to 100 indicating good (≥ 60), moderate (40-59) or unfavorable (< 40) HRQoL. Two-thirds of the entire chronic TBI cohort (102 males; 33 females) aged 18-85 years reported good HRQoL up to 10 years after TBI. TBI etiology differed between sexes with females suffering more often from traffic- than fall-related TBI (p = 0.01) with increasing prevalence during aging (p = < 0.001). HRQoL (good/moderate/unfavorable) differed between sexes (p < 0.0001) with 17% more females reporting moderate outcome (p = 0.01). Specifically, older females (54-76-years at TBI) were affected, while males constantly reported good HRQoL (p = 0.017). Cognition (p = 0.014), self-perception (p = 0.009), and emotions (p = 0.016) rather than physical problems (p = 0.1) constrained older females' HRQoL after TBI. Experiencing TBI during aging does not influence HRQoL outcome in males but females suggesting that female brains cope less well with a traumatic injury during aging. Therefore, older females need long-term follow-ups after TBI to detect neuropsychiatric sequels that restrict their quality of life. Further investigations are necessary to uncover the mechanisms of this so far unknown phenomenon.