Psychometric Evaluation and Misophonic Experience in a Portuguese-Speaking Sample.

Misophonia, a disorder characterised by an extreme sensitivity to certain sounds, is increasingly being studied in cross-cultural settings. The S-Five scale is a multidimensional psychometric tool initially developed to measure the severity of misophonia in English-speaking populations. The scale has been validated in several languages, and the present study aimed to validate the European Portuguese S-Five scale in a Portuguese-speaking sample. The scale was translated into Portuguese using a forward-backwards translation method. The psychometric properties of the S-Five scale were evaluated in a sample of 491 Portuguese-speaking adults. Confirmatory factor analysis supported a five-factor structure consistent with previous versions of the S-Five scale. The five factors were as follows: (1) internalising appraisals, (2) externalising appraisals, (3) perceived threat and avoidance behaviour, (4) outbursts, and (5) impact on functioning. The satisfactory psychometric properties of the S-Five scale further indicated its cross-cultural stability. As a psychometrically robust tool, the S-Five can measure misophonia in Portuguese-speaking populations, allowing future studies to explore and compare misophonia in this population.

White matter hyperintensities in bipolar disorder: systematic review and meta-analysis.

Background: White matter hyperintensities are lesions of presumed vascular origin associated with Cerebral small vessel disease. WMH are common findings that and are associated with increased risk of cognitive impairment and dementia. A higher prevalence of WMH has been also reported in patients with bipolar disorder (BD), although the evidence is conflicting. Objective: To compare the prevalence of WMH in adults with BD, with the prevalence found in healthy controls. Methods: We searched the Embase, Medline/PubMed, and references cited in articles retrieved on May 20, 2023. We included case-control studies that compared the prevalence of WMH in adult BD patients with the prevalence of WMH in healthy controls, using T2-weighted magnetic resonance imaging. We performed a meta-analysis using a random-effects method based on the inverse-variance approach. Findings: We included 22 case-control studies reporting data of 1313 people. The overall rate of WMH was 46.5% in BD patients and 28% in controls (pooled Odds Ratio 2.89, 95% CI 1.76; 4.75). We found a moderate heterogeneity across studies (I2 = 0.49). Publication bias was not significant. Interpretation: We found evidence that BD patients have a higher burden of WMH than healthy controls. Main limitations were impossibility of analyzing gender differences and bipolar type, moderate heterogeneity between studies, non-representative samples, lack of control for major confounders and search in two electronic databases. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023428464.

In vivo molecular imaging of the neuroinflammatory response to peripheral acute bacterial infection in older patients with cognitive dysfunction: A cross-sectional controlled study.

Introduction: Chronic neuroinflammatory events have been implicated in the pathophysiology of neurodegenerative conditions but no studies have directly examined the neuroinflammatory response to acute systemic infection in older people with dementia. The objective of this study was to determine the magnitude of the neuroinflammatory response triggered by acute systemic infection in older subjects with dementia and/or delirium compared to cognitively healthy controls. Methods: We recruited 19 participants (4 with delirium, 4 with dementia, 4 with delirium superimposed on dementia, 7 cognitively healthy) hospitalized with acute systemic bacterial infection not involving the Central Nervous System. Participants underwent [11C]-PK11195 PET and a neuropsychological assessment during hospital stay. The distribution volume ratio was estimated in the regions-of-interest using the Hammers' brain atlas. Results: In the subcortical analysis, we found that the cognitively healthy group presented regions with significantly higher DVR intensity than the other groups in the choroid plexus. Mean choroid plexus DVR positively correlated with MoCA (r = 0.66, p = 0.036). Conclusion: This study suggests that dementia and/or delirium is associated with a reduced neuroinflammatory response to acute systemic bacterial infection which can be the result of an immunosuppressive brain environment.

Peripheral inflammatory markers during an acute bacterial infection in older patients with and without cognitive dysfunction: A case control study.

Dementia is a known risk factor for acute bacterial infections which may also play a significant role in promoting or accelerating cognitive impairment. Pneumonia and urinary tract infections are the main cause of hospitalisation of dementia patients and infections are a major precipitant of delirium. It is well established that peripheral immune signals induce a neuroinflammatory response largely mediated by microglial cells which is amplified with advanced age, neurodegenerative disorders and genetic characteristics. Reversely, the innate immune response to acute bacterial infection is tightly regulated by the brain. It remains unclear whether dysfunctional neural circuits affected by dementia and/or delirium could alter systemic innate immune responses at the periphery. The current study aims to determine if dementia and/or delirium are associated with an altered systemic inflammatory response to an acute bacterial infection. We recruited 46 hospitalised older patients with acute bacterial infections. From these, 29 participants had cognitive dysfunction (6 with delirium, 12 with dementia and 11 with delirium superimposed on dementia) and 17 had normal cognition. We also included a control group of 11 patients with dementia but with no current infection matched for age and educational status. Baseline characteristics were tested between groups using Kruskal-Wallis test and pairwise comparisons were subsequently assessed with Bonferroni correction for multiple comparisons for continuous variables. Chi square test was used to assess differences between groups in categorical data and correlations between peripheral inflammatory parameters were assessed with Spearman's test. The 4 groups with infection and the control group with no infection had similar characteristics except for cognitive function and functionality which was higher for the group of infected cognitively healthy participants. Levels of C-reactive protein were similar between the infected groups and higher than the non-infected dementia group. Infected patients with cognitive dysfunction (delirium and/or dementia) had higher serum levels of IL-6, TNF-alpha and IL-1beta. These participants had reduced expression of miR-145 in circulating exosomes which correlated negatively with miR-155 levels (r = -0.411, p = 0.027). Expression of CR1 in circulating CD14+ monocytes was higher in infected participants with cognitive dysfunction and, in this group, PICALM correlated both with TNF-alpha and IL-6. In contrast to what was observed in participants with normal cognition, expression of CR1 did not correlate with DAP12 in infected participants with cognitive dysfunction. Taken together, our findings suggest that cognitive dysfunction is associated with an exaggerated proinflammatory response during acute bacterial infection with deregulation of several molecular signalling pathways in circulating exosomes and in monocytes.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis presenting with a postpartum psychosis.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a rare condition characterised by neuropsychiatric symptoms, presence of antithyroid antibodies and significant response to steroid therapy. Postpartum psychosis (PP), although having a low prevalence, is a psychiatrical emergency with potentially serious impact in the mother and children. PP has an atypical presentation when compared with affective or psychotic episodes unrelated to pregnancy. Autoimmune dysfunction is frequent in the postpartum period and is closely related to PP. We report a case of a primiparous woman in her 20s with PP who did not respond to initial treatment with antipsychotics. After reassessment, SREAT was considered in the differential diagnosis. Neuropsychiatric symptoms improved dramatically after 72 hours of treatment with high-dose steroids treatment and the patient was discharged after 16 days. In women with PP, an autoimmune cause must be ruled out before assuming a psychiatry aetiology.

Delirium awareness day: a portuguese perspective.

Delirium is a syndrome characterized by impairment of awareness and inattention, that represents a change from the patient's baseline cognitive functioning. It is triggered by an underlying medical condition, reaching a prevalence of 24.7% in geriatric wards. However, undiagnosed delirium remains a reality among inpatient individuals, with an estimated frequency of 24.1%. The inappropriate knowledge of diagnostic criteria and standard screening tools was pointed out as a relevant contributing factor to this paradigm. Liaison Psychiatry Services guarantee psychiatric approach and treatment to patients attending general hospitals. Considering that older adult patient care requires a well-trained and skilled team, the Centro Hospitalar e Universitário de Coimbra has a Geriatric Psychiatry Liaison Service, where delirium is one of the prevailing clinical conditions assessed by this team. The International Delirium Awareness Day is going to be worldwide celebrated on the 11th of March. Given that delirium has been consistently associated with the economic burden and adverse outcomes this symbolic day works as a huge opportunity to raise insight into the preventive strategies that could be implemented among healthcare professionals, patients, and caregivers. Within the Portuguese National Health System there is a need to build a set of systematic epidemiological data about delirium prevalence and incidence in the different settings and it would be essential the employment of a multicomponent intervention package delivered by a multidisciplinary team trained and competent in delirium prevention into routine care.

Cognitive Trajectories Following Acute Infection in Older Patients With and Without Cognitive Impairment: An 1-Year Follow-Up Study.

Introduction: Dementia is a known risk factor for both delirium and acute systemic infections which may also play a significant role in promoting or accelerating neurodegenerative disease. Infections are both the main causes of hospitalization of dementia patients and can be a major precipitant of delirium but currently it is not possible to predict the risk of cognitive decline in older patients exposed to acute infection. Objectives: We aimed to determine the level of cognitive change at 1-year follow up in individuals with different patterns of cognitive function (dementia, delirium, delirium superimposed on dementia) at the time of their hospitalization due to a systemic infection and to correlate these cognitive patterns with clinical status variables. Methods: We recruited 53 hospitalized geriatric patients with a systemic infection, and we collected 12-months follow up data for 34 patients. These patients were classified in four groups: no cognitive impairment (controls-C), delirium only (D), dementia only (Dem), and delirium superimposed to dementia (DD). Cognitive performance was measured by change in score on the Montreal Cognitive Assessment (MoCA) and delirium was identified using Confusion Assessment Measure (CAM). We examined performance on the MoCA in the first year after hospitalization, controlling for demographic characteristics, coexisting medical conditions, and type of infection. Results: For the 34 patients to whom follow-up data was available, delirium presence in individuals with prior dementia (DD group) was associated with a negative mean change score of 3-point (p < 0.02) at 1 year follow up, whereas dementia patients without delirium had a mean change score of 1.5-point lower at 12-months (p = 0.04), when comparing follow-up and baseline MoCA scores. Cognitively healthy patients did not significantly decrease their MoCA score at follow-up (p = 0.15). MoCA and NPI scores during hospitalization were significantly correlated with the level of cognitive decline in the four groups (r = 0.658, p < 0.01 and r = 0.439, p = 0.02, respectively). Conclusions: Premorbid dementia and delirium superimposed on dementia during hospitalization in older patients with acute infections predict cognitive decline at 1 year following admission. Taken together, our findings suggest a pathophysiological interaction between neurodegenerative changes, acute infection, and delirium.

Estimates of Geriatric Delirium Frequency in Noncardiac Surgeries and Its Evaluation Across the Years: A Systematic Review and Meta-analysis.

OBJECTIVES: Delirium is an acute neuropsychiatric syndrome associated with poor outcomes. Older adults undergoing surgery have a higher risk of manifesting perioperative delirium, particularly those having associated comorbidities. It remains unclear whether delirium frequency varies across surgical settings and if it has remained stable across the years. We conducted a systematic review to (1) determine the overall frequency of delirium in older people undergoing noncardiac surgery; (2) explore factors explaining the variability of the estimates; and (3) determine the changing of the estimates over the past 2 decades. DESIGN: Systematic review and meta-analysis. Literature search was performed in MEDLINE, PubMed, ISI Web of Science, EBSCO, ISRCTN registry, ScienceDirect, and Embase in January 2020 for studies published from 1995 to 2020. SETTING: Noncardiac surgical settings. PARTICIPANTS: Forty-nine studies were included with a total of 26,865 patients screened for delirium. METHODS: We included observational and controlled trials reporting incidence, prevalence, or proportion of delirium in adults aged ≥60 years undergoing any noncardiac surgery requiring hospitalization. Data extracted included sample size, reported delirium frequencies, surgery type, anesthesia type, delirium diagnosis method, length of hospitalization, and year of assessment. (PROSPERO registration no.: CRD42020160045). RESULTS: We found an overall pooled frequency of preoperative delirium of 17.9% and postoperative delirium (POD) of 23.8%. The POD estimates increased between 1995 and 2020 at an average rate of 3% per year. Pooled estimates of POD were significantly higher in studies not excluding patients with lower cognitive performance before surgery (28% vs 16%) and when general anesthesia was used in comparison to local, spinal, or epidural anesthesia (28% vs 20%). CONCLUSIONS AND IMPLICATIONS: Type of anesthesia and preoperative cognitive status were significant moderators of delirium frequency. POD in noncardiac surgery has been increasing across the years, suggesting that more resources should be allocated to delirium prevention and management.

[Portuguese Consensus on the Diagnosis and Management of Lewy Body Dementia (PORTUCALE)]. / Consenso Português para o Diagnóstico e Gestão Clínica da Demência com Corpos de Lewy (PORTUCALE).

Lewy body dementia is a common cause of dementia leading to the progressive deterioration of cognitive function and motor skills, behavioral changes, and loss of autonomy, impairing the quality of life of patients and their families. Even though it is the second leading cause of neurodegenerative dementia, diagnosis is still challenging, due to its heterogenous clinical presentation, especially in the early stages of the disease. Accordingly, Lewy body dementia is often misdiagnosed and clinically mismanaged. The lack of diagnostic accuracy has important implications for patients, given their increased susceptibility to the adverse effects of certain drugs, such as antipsychotics, which may worsen some symptoms associated with Lewy body dementia. Therefore, a specialist consensus based on the analysis of the most updated and relevant literature, and on clinical experience, is useful to all professionals involved in the care of these patients. This work aims to inform and provide recommendations about the best diagnostic and therapeutic approaches in Lewy body dementia in Portugal. Moreover, we suggest some strategies in order to raise the awareness of physicians, policy makers, and the society at large regarding this disease.

A demência com corpos de Lewy é uma causa comum de demência, provocando a perda progressiva de funções cognitivas e capacidades motoras, alterações comportamentais, e perda de autonomia, com compromisso da qualidade de vida dos doentes e seus familiares. Apesar de ser a segunda causa mais frequente de demência neurodegenerativa, o diagnóstico mantém-se um desafio, devido à sua apresentação clínica heterogénea, sobretudo nas fases iniciais da doença. Por conseguinte, a demência com corpos de Lewy é frequentemente mal diagnosticada e clinicamente gerida de forma insuficiente. A falta de acuidade diagnóstica tem implicações significativas para os doentes, dada a maior suscetibilidade aos efeitos adversos de determinados fármacos, tais como os antipsicóticos, que podem agravar alguns sintomas associados à demência com corpos de Lewy. Por conseguinte, um consenso de especialistas, baseado na análise da literatura mais atual e relevante, e na experiência clínica, é útil para todos os profissionais envolvidos no cuidado destes doentes. O objetivo deste trabalho é informar e gerar recomendações acerca das melhores abordagens diagnóstica e terapêutica da demência com corpos de Lewy em Portugal. Além disso, sugerimos estratégias para aumentar a sensibilização dos médicos, dos decisores políticos e da sociedade em geral em relação a esta doença.

Arousal changes and delirium in acute medically-ill male older patients with and without dementia: a prospective study during hospitalization.

Objectives: Previous research has characterized the prevalence, natural course and outcomes of delirium superimposed in dementia but much less is known about the relation between preexisting dementia and the emergence of altered arousal (such as drowsiness, obtundation, stupor or agitation) during acute medical illness. This study aimed to determine the natural course of delirium and abnormal arousal states in acute medically-ill older patients with and without prior dementia during hospital stay.Methods: Observational prospective study in an acute male geriatric ward. Patients aged ≥ 65 years old were assessed by a psychiatrist within the first 72h of admission and in every other day until discharge to determine the level of arousal and the presence of delirium. Prior cognitive impairment, sociodemographic data, chronic comorbidities, psychotropic prescription and functional status were assessed at baseline.Results: 43.5% of participants in the final sample (n= 269) had dementia. Prior dementia was associated with higher rates of moderate/severe hypoarousal (29.9% vs. 4.6%; p<0.001) and delirium (20.5% vs. 7.2%; p<0.001) at admission. RASS ≤ -3 at admission predicted a 4-fold increased intra-hospital mortality risk and RASS ≠ 0 had a sensitivity of 82.8% and a specificity of85.9% for delirium.Conclusions: Moderate/severe hypoarousal is associated with adverse outcomes and should be assessed as part of delirium spectrum, particularly in subjects with prior dementia.

ADHD Among Offenders: Prevalence and Relationship With Psychopathic Traits.

Objective: Longitudinal studies have shown a strong association between ADHD and criminal behavior. The aims of this study were to examine the prevalence of adult ADHD in a high-security facility and to investigate the relationship between ADHD symptoms and psychopathic traits in criminal offenders. Material and Methods: Participants were recruited between October 2015 and January 2016 among the inmates from a high-security all-male correctional facility in Portugal. Self-report scales were used to measure ADHD symptoms, current psychopathology, and psychopathic traits. An interview was conducted to collect sociodemographic data, along with information about adverse childhood experiences, substance use, and criminal record. The statistical analysis was conducted using STATA 13 with the significance level set at .05. Results: From the final sample of 101 male prisoners, 17 participants (16.8%) screened positive for ADHD. Participants positive for ADHD had higher levels of general psychopathology and psychopathic traits. Psychopathic traits remained significantly higher in ADHD offenders after controlling for age, substance abuse, and early childhood adversities (OR = 1.07, p = .002) and this was explained by differences in the Meanness subscale (OR = 1.11, p = .013). Discussion/conclusions: The present study shows that ADHD symptoms are highly prevalent among offenders and might have a modulating effect on the course of delinquent behavior. The cross-sectional association between ADHD symptoms and psychopathic traits reinforces the previously documented correlation between these disorders and can lead to a better understanding of the prevalent criminal behavior in ADHD patients.

Impairments in balance and mobility identify delirium in patients with comorbid dementia.

ABSTRACTDiagnosing delirium superimposed on dementia (DSD) remains challenging because of a lack of specific tools, though motor dysfunction in delirium has been relatively under-explored. This study aimed to use dysfunction in balance and mobility (with the Hierarchical Assessment of Balance And Mobility: HABAM) to identify DSD. This is a cross-sectional multicenter study, recruiting consecutive patients ≥70 years admitted to five acute or rehabilitation hospitals in Ireland, Italy, Portugal, and Switzerland. Delirium was diagnosed using DSM-5 criteria; dementia was determined by the Mini-Mental State Examination and the Questionnaire of Cognitive Decline in the Elderly. HABAM score was recorded at admission. Out of 114 patients (mean age ± SD = 82 ± 7; 54% female), dementia alone was present in 24.6% (n = 28), delirium alone in 18.4% (n = 21) and DSD in 27.2% (n = 31). Patients with DSD had a mean HABAM score 7 points greater than those with dementia alone (19.8 ± 8.7 vs 12.5 ± 9.5; p < 0.001); 70% of participants with DSD were correctly identified using the HABAM at a cut off of 22 (sensitivity 61%, specificity 79%, AUC = 0.76). Individuals with delirium have worse motor function than those without delirium, even in the context of comorbid dementia. Measuring motor function using the HABAM in older people at admission may help to diagnose DSD.

Higher Autistic Traits Among Criminals, But No Link to Psychopathy: Findings from a High-Security Prison in Portugal.

The relationship between autism, criminality and psychopathy has gained increased attention in recent years, although research has focused on autism spectrum disorders, and not autistic traits. We measured autistic traits (with the Autism Spectrum Quotient) in a sample of 101 inmates from a high-security prison and compared them to a control group, using a logistic regression model that included age, education, psychopathology, psychopathy and attention deficit-hyperactivity disorder as covariates. Prisoners had more autistic traits (OR 1.13, p = 0.002) due to higher scores in the communication (OR 1.23) and imagination (OR 1.30) domains. No correlations were found between autistic and psychopathic traits. Our study points to the presence of autistic traits as being independent risk factors for imprisonment, although not associated with psychopathy.

Detecting delirium superimposed on dementia: diagnostic accuracy of a simple combined arousal and attention testing procedure.

BACKGROUND: Detecting delirium superimposed on dementia (DSD) can be challenging because assessment partly relies on cognitive tests that may be abnormal in both conditions. We hypothesized that a combined arousal and attention testing procedure would accurately detect DSD. METHODS: Patients aged ≥70 years were recruited from five hospitals across Europe. Delirium was diagnosed by physicians using DSM-5 criteria using information from nurses, carers, and medical records. Dementia was ascertained by the Informant Questionnaire on Cognitive Decline in the Elderly. Arousal was measured using the Observational Scale of Level of Arousal (OSLA), which assesses eye opening, eye contact, posture, movement, and communication. Attention was measured by participants signaling each time an "A" was heard when "S-A-V-E-A-H-A-A-R-T" was read out. RESULTS: The sample included 114 persons (mean age 82 years (SD 7); 54% women). Dementia alone was present in 25% (n = 28), delirium alone in 18% (n = 21), DSD in 27% (n = 31), and neither in 30% (n = 34). Arousal and attention was assessed in n = 109 (96%). Using OSLA, 83% participants were correctly identified as having delirium (sensitivity 85%, specificity 82%, AUROC 0.92). The attention task correctly classified 76% of participants with delirium (sensitivity 90%, specificity 64%, AUROC 0.80). Combining scores correctly classified 91% of participants with delirium (sensitivity 84%, specificity 92%, AUROC 0.94). Diagnostic accuracy remained high in the subgroup with dementia (93% correctly classified, sensitivity 94%, specificity 92%, AUROC 0.98). CONCLUSIONS: This combined arousal-attention assessment to detect DSD was brief yet had high diagnostic accuracy. Such an approach could have clinical utility for diagnosing DSD.

Detecting Delirium Superimposed on Dementia: Evaluation of the Diagnostic Performance of the Richmond Agitation and Sedation Scale.

OBJECTIVES: Delirium disproportionately affects patients with dementia and is associated with adverse outcomes. The diagnosis of delirium superimposed on dementia (DSD), however, can be challenging due to several factors, including the absence of caregivers or the severity of preexisting cognitive impairment. Altered level of consciousness has been advocated as a possible useful indicator of delirium in this population. Here we evaluated the performance of the Richmond Agitation and Sedation Scale (RASS) and the modified-RASS (m-RASS), an ultra-brief measure of the level of consciousness, in the diagnosis of DSD. DESIGN: Multicenter prospective observational study. RASS and m-RASS results were analyzed together, labeled RASS/m-RASS. SETTING: Acute geriatric wards, in-hospital rehabilitation, emergency department. PARTICIPANTS: Patients 65 years and older with dementia. MEASUREMENTS: Delirium was diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) or with the Delirium Rating Scale-Revised (DRS-R-98), or with the 4 A's Test (4AT). Dementia was detected with the Clinical Dementia Rating (CDR) Scale, the Short Form-Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) or via the clinical records. RESULTS: Of the 645 patients included, 376 (58%) had delirium. According to the instrument used to evaluate delirium, the prevalence was 66% with the 4AT, 23% with the DSM, and 100% with the DRS-R-98. Overall a RASS/m-RASS score other than 0 was 70.5% sensitive (95% confidence interval [CI] 65.9%-75.1%) and 84.8% (CI 80.5%-89.1%) specific for DSD. Using a RASS/m-RASS value greater than +1 or less than -1 as a cutoff, the sensitivity was 30.6% (CI 25.9%-35.2%) and the specificity was 95.5% (CI 93.1%-98.0%). The sensitivity and the specificity did not greatly vary according to the method of delirium diagnosis and the dementia ascertainment, although the specificity was slightly higher when the DSM and the IQCODE were used. CONCLUSION: In older patients admitted to different clinical settings, the RASS and m-RASS analyzed as a single group had moderate sensitivity and very high specificity for the detection of DSD. Level of consciousness is therefore a valuable clinical indicator that should form part of delirium screening strategies, although for higher sensitivity other methods of assessment should be used.

Identification of sub-groups in acutely ill elderly patients with delirium: a cluster analysis.

BACKGROUND: Delirium is a serious neuropsychiatric syndrome affecting mainly elderly participants with acute medical diseases. The pathophysiology of delirium remains poorly understood as it involves complex dynamic interactions between a diversity of risk factors. Exploring how etiological factors interact with each other can clarify the pathophysiological mechanisms and facilitate the early identification of this syndrome. The aim of this study was to explore how different risk factors co-occur in medically ill elderly patients with delirium with cluster analysis and identify clinically meaningful sub-groups in this population. METHODS: A cross-sectional study was developed. Ninety-nine elderly inpatients admitted to acute medical wards diagnosed with delirium during hospitalization were selected. For each patient sociodemographic characteristics, acute and chronic medical conditions, laboratory parameters, and current medication were collected. RESULTS: The cluster analysis extracted three distinct subgroups of participants with delirium. Patients in cluster 1 (n = 28) had higher rates of medication with anticholinergic proprieties. Cluster 2 (n = 29) included participants with cardiac and pulmonary comorbidities associated with both chronic and acute reduction of blood flow and/or oxygenation to the brain. Cluster 3 (n = 42 patients) comprised patients with simultaneous deregulation of different organs/systems, such as electrolytic disturbances, metabolic disturbances, and acute renal failure. Known predisposing factors of delirium, such as age and pre-existing dementia, were similar between groups. CONCLUSIONS: The results reveal different patterns of clinical characteristics in elderly patients with delirium. This is relevant to clinical care of acute medically ill patients and suggests that different pathways are implicated in delirium pathophysiology.

The immunology of delirium.

Delirium is an acute neuropsychiatric syndrome characterized by acute-onset global cognitive deficits, perceptual and behavioural disturbances affecting mainly elderly subjects with underlying medical or surgical conditions. The pathophysiology of delirium is complex and inflammation is a relevant precipitant factor of this syndrome, although it remains unclear how acute systemic inflammation induces the clinical picture of delirium. The central nervous system is able to detect peripheral infection or tissue destruction through circulating immune mediators and neural ascending signs. Activated microglia is responsible for an acute neuroinflammatory reaction underlying the symptoms of sickness. In healthy conditions descending pathways from the paraventricular nucleus, locus coeruleus and dorsal motor nucleus organize a centralized response to influence the immune response at the periphery and restore homeostasis. In the context of ageing and chronic neurodegeneration, adaptive changes to acute insults are characterized by exaggerated production of pro-inflammatory cytokines by primed microglia coupled with dysfunction of brain-to-immune pathways. In animal models, these changes underlie a more severe manifestation of sickness behaviour with working memory deficits suggesting that inattention, a core feature of delirium, can be a clinical correlate of an increased neuroinflammatory reaction. In patients with delirium, higher levels of pro-inflammatory cytokines and cortisol were identified in plasma and cerebrospinal fluid. However, to date it has not been clarified how peripheral inflammatory or endocrine biomarkers can reflect the likelihood or severity of delirium symptoms. In the future, a better understanding of the interaction between the brain and peripheral organs and the exact mechanism by which systemic inflammation can lead to delirium, will allow the development of new therapeutic agents.

An insulinoma presenting with hypochondriac delusions and food refusal.

The authors report a case of a 68-year-old man with an unrecognized insulinoma manifesting with neuropsychiatric symptoms. For two years, he presented with unspecified behavior changes, autonomic and neuroglycopenic symptoms, which led him to be misdiagnosed with a neurologic and psychiatric disorder before the insulinoma was recognized. Following neurological alterations in context of hypoglycemia, subsequent to longstanding food refusal, he was admitted in the psychiatric ward. Despite good global response and normal food intake, hypoglycemic episodes were still occurring and led to a careful evaluation which permitted the definitive diagnostic. This case highlights the diagnostic difficulties of medical disorders presenting with clinical features overlapping neurological and psychiatric syndromes. It also reflects the diagnostic difficulties in rare clinical entities, particularly in patients previously followed in psychiatry and underlines the need for a constant dialogue and updating of clinicians.

The stress response to surgery and postoperative delirium: evidence of hypothalamic-pituitary-adrenal axis hyperresponsiveness and decreased suppression of the GH/IGF-1 Axis.

INTRODUCTION: The aim of this study is to determine whether postoperative delirium is associated with dysregulation of hypothalamic-pituitary-adrenal and growth hormone/insulin-like growth factor 1 (GH/IGF-1) responses following acute systemic inflammation. METHODS: Plasma levels of cortisol, IGF-1, C-reactive protein, interleukin (IL)-6, IL-8, and IL-10 were measured before and after surgery in 101 patients ≥ 60 years without dementia undergoing elective hip arthroplasty. Participants were assessed with confusion assessment method and Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision; DSM-IV-TR) postoperatively and 37 patients fulfilled the DSM-IV-TR criteria for delirium. RESULTS: Preoperative plasma cortisol levels were similar in delirium and nondelirium groups (405.37 ± 189.04 vs 461.83 ± 219.39; P = .22). Participants with delirium had higher postoperative cortisol levels (821.67 ± 367.17 vs 599.58 ± 214.94; P = .002) with enhanced postoperative elevation in relation to baseline (1.9- vs 1.5-fold; P = .004). The plasma levels of IGF1 did not differ in delirium and nondelirium groups before (18.12 ± 7.58 vs 16.8 ± 7.86; P = .477) and following surgery (13.39 ± 5.94 vs 11.12 ± 6.2; P = .639), but the levels increased in relation to baseline more frequently in patients who developed delirium (24.3% vs 7.8%; P = .034). The magnitude of postoperative cortisol elevation correlated with ΔIL-6 (P = .485; P = .002), ΔIL-8 (P = .429; P = .008), and ΔIL-10 (P = .544; P < .001) only in patients with delirium. CONCLUSIONS: Hypothalamic-pituitary-adrenal axis hyperresponsiveness and a less frequent suppression of the GH/IGF-1 axis in response to acute stress are possibly involved in delirium pathophysiology.