COVID-19 restrictions promoted the newly occurring loneliness in older people - a prospective study in a memory clinic population.

Introduction: A high burden and many negative outcomes for older people were associated with the COVID-19 pandemic. Social isolation and loneliness are prevalent health problems impacting well-being and quality of life and may have increased due to pandemic-related restrictions. Methods: This study investigate the influence of the COVID-19 pandemic on loneliness in people visiting a mem40ory clinic between March 2020 and September 2022. We conducted a prospective, single-center, questionnaire-based observational follow-up study to assess potential predictors of newly occurring, pandemic-related loneliness. Next to a newly developed COVID-19 questionnaire, a comprehensive neuropsychological test battery, the Neuropsychiatric Inventory and the Geriatric Depression Scale were used. Results: In total 426 people (mean age: 76.48 years, 12.9% cognitively intact, 33.1% diagnosed with Mild Cognitive Impairment, 49.8% diagnosed with dementia, and 4.2% diagnosed with depression) completed the COVID-19 questionnaire at baseline and 166 at follow-up. Newly occurring loneliness was indicated by 22.3% of baseline participants and by 24.1% of follow-up participants. Results of logistic regression analysis showed that living alone (OR 5.452) and having less contact with friends (OR 2.771) were most predictive of the occurrence of loneliness. The use of digital communication media as an alternative strategy for social interaction was lowest in dementia patients (6-13%). Discussion: In conclusion, personal contacts and a close friendship network appear to be more decisive to prevent loneliness in older people than does the use of digital communication media. However, promoting an intensified use of digital communication media may be useful to counteract loneliness, especially in dementia patients.

Long-term impact of resilience and extraversion on psychological distress during the COVID-19 pandemic: a longitudinal investigation among individuals with and without mental health disorders.

Background: Over the past years, the COVID-19 pandemic has caused significant disruptions in daily routines. Although the pandemic has affected almost everyone, it has been particularly challenging for people with pre-existing mental health conditions. Therefore, this study investigated the long-term impact of resilience and extraversion on psychological distress in individuals diagnosed with mental health disorders (MHD) compared to the general population. In addition, possible gender-specific differences were investigated. Methods: 123 patients with pre-existing MHD and 343 control subjects from Austria and Italy participated in three online surveys that had been conducted after the initial wave of the COVID-19 pandemic (t0), during the second lockdown in both countries (t1), and one year thereafter (t2). Participants completed standardized questionnaires on psychological distress (Brief-Symptom-Checklist), resilience (Resilience Scale), and extraversion (Big Five Inventory). A mediation model was employed to test the primary hypothesis. Possible gender-specific differences were analyzed using a moderated mediation model. Results: The prevalence of psychological distress was consistently higher in patients compared to controls (t0: 37.3% vs. 13.2%, t1: 38.2% vs 11.7%, t2: 37.4% vs. 13.1%). This between-group difference in psychological distress at the first follow-up was fully mediated by baseline resilience scores (65.4% of the total effect). During the second-follow up, extraversion accounted for 18% of the total effect, whereas resilience slightly decreased to 56% of the total effect. Gender was not a significant moderator in the model. Conclusion: Next to showing that people with MHD were particularly affected by the pandemic, these findings indicate that higher degrees of resilience and extraversion are related to less long-term psychological distress. Our findings stress the relevance of strengthening resilience and extraversion and to provide mental health support in times of crises, both to patients with MHD and the general population.

Relevance of spirituality and perceived social support to mental health of people with pre-existing mental health disorders during the COVID-19 pandemic: a longitudinal investigation.

BACKGROUND: The COVID-19 pandemic and related measures have negatively impacted mental health worldwide. The main objective of the present longitudinal study was to investigate mental health in people living in Tyrol (Austria) and South Tyrol (Italy) during the COVID-19 pandemic and to report the prevalence of psychological distress among individuals with versus those without pre-existing mental health disorders (MHD) in the long-term (summer 2020-winter 2022). Here, we specifically focus on the relevance of spirituality and perceived social support in this regard. METHODS: 161 individuals who had been diagnosed with MHD and 446 reference subjects participated in this online survey. Electronic data capture was conducted using the Computer-based Health Evaluation System and included both sociodemographic and clinical aspects as well as standardized questionnaires on psychological distress, spirituality, and the perception of social support. RESULTS: The prevalence of psychological distress was significantly higher in individuals with MHD (36.6% vs. 12.3%) and remained unchanged among both groups over time. At baseline, the perception of social support was significantly higher in healthy control subjects, whereas the two groups were comparable in regards of the subjective relevance of faith. Reference subjects indicated significantly higher spiritual well-being in terms of the sense of meaning in life and peacefulness, which mediated in large part the between-group difference of psychological distress at follow-up. Notably, both faith and the perception of social support did not prove to be relevant in this context. CONCLUSIONS: These findings point to a consistently high prevalence of psychological distress among people suffering from MHD and underscore the prominent role of meaning in life and peacefulness as a protective factor in times of crisis. Therapeutic strategies that specifically target spirituality may have a beneficial impact on mental health.

Consequences and Perception of the COVID-19 Pandemic on Patients and Caregivers in an Austrian Memory Clinic Population One Year After Pandemic Onset.

BACKGROUND: The COVID-19 pandemic was associated with high mortality and negative consequences for patients with Alzheimer's disease or dementia and their caregivers. Memory clinics play an important role in enabling early dementia diagnosis and providing support for patients and their caregivers. OBJECTIVE: This study investigates the impact of the COVID-19 pandemic and its restrictions on patients of a memory clinic and their caregivers between March 2020 and March 2021. METHODS: We conducted a prospective, single-center, questionnaire-based, observational study to assess consequences and perception of the COVID-19 pandemic on emotion, cognitive function, social living, areas of care, and information retrieval. RESULTS: Results of 255 participants' (mean age 76.78, SD 8.9; 12% cognitively intact, 33% mild cognitive impairment, 55% dementia) and 203 caregivers' COVID-19 questionnaires (valid response rate 71%) could be included in the study. Participants reported a prevalence of psychological symptoms associated with the pandemic between 3-20%. Caregivers living outside compared to those living with the participant reported higher rates of new onset or worsening of neuropsychiatric symptoms in participants since pandemic onset. Patients with dementia showed the lowest use of digital communication before (15.7%) and after (17.1%) pandemic onset in the diagnostic groups. CONCLUSION: The COVID-19 pandemic frequently led to social isolation and reduced cognitive stimulation due to restrictions in elderly persons with cognitive deficits resulting in negative effects on emotional and social levels. We hypothesize that the implementation and sensitization with digital communication in clinical routine could provide a useful tool to counteract these negative effects.

Efficacy of oral versus long-acting antipsychotic treatment in patients with early-phase schizophrenia in Europe and Israel: a large-scale, open-label, randomised trial (EULAST).

BACKGROUND: Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved. We aimed to compare time to all-cause discontinuation in patients randomly allocated to long-acting injectable (LAI) versus oral medication. METHODS: EULAST was a pragmatic, randomised, open-label trial conducted at 50 general hospitals and psychiatric specialty clinics in 15 European countries and Israel. Patients aged 18 years and older, with DSM-IV schizophrenia (as confirmed by the Mini International Neuropsychiatric Interview 5 plus) and having experienced their first psychotic episode from 6 months to 7 years before screening, were randomly allocated (1:1:1:1) using block randomisation to LAI paliperidone, LAI aripiprazole, or the respective oral formulations of these antipsychotics. Randomisation was stratified by country and duration of illness (6 months up to 3 years vs 4 to 7 years). Patients were followed up for up to 19 months. The primary endpoint was discontinuation, regardless of the reason, during 19 months of treatment. We used survival analysis to assess the time until all-cause discontinuation in the intention-to-treat (ITT) group, and per protocol analyses were also done. This trial is registered with ClinicalTrials.gov, NCT02146547, and is complete. FINDINGS: Between Feb 24, 2015, and Dec 15, 2018, 533 individuals were recruited and assessed for eligibility. The ITT population included 511 participants, with 171 (33%) women and 340 (67%) men, and a mean age of 30·5 (SD 9·6) years. 410 (80%) of 511 participants were White, 35 (7%) were Black, 20 (4%) were Asian, and 46 (9%) were other ethnicity. In the combined oral antipsychotics treatment group of 247 patients, 72 (29%) patients completed the study and 175 (71%) met all-cause discontinuation criteria. In the combined LAI treatment arm of 264 patients, 95 (36%) completed the study and 169 (64%) met the all-cause discontinuation criteria. Cox regression analyses showed that treatment discontinuation for any cause did not differ between the two combined treatment groups (hazard ration [HR] 1·16, 95% CI 0·94-1·43, p=0·18). No significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (log rank test χ2=1·87 [df 1]; p=0·17). During the study, 121 psychiatric hospitalisations occurred in 103 patients, and one patient from each of the LAI groups died; the death of the patient assigned to paliperidone was assessed to be unrelated to the medication, but the cause of other patient's death was not shared with the study team. 86 (25%) of 350 participants with available data met akathisia criteria and 70 (20%) met parkinsonism criteria at some point during the study. INTERPRETATION: We found no substantial advantage for LAI antipsychotic treatment over oral treatment regarding time to discontinuation in patients with early-phase schizophrenia, indicating that there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice. FUNDING: Lundbeck and Otsuka.

Add-on treatment with Cerebrolysin improves clinical symptoms in patients with ALS: results from a prospective, single-center, placebo-controlled, randomized, double-blind, phase II study.

Amyotrophic lateral sclerosis (ALS) is a devastating and progressive neurodegenerative disease with limited treatment options available. Cerebrolysin is a drug candidate for the treatment of ALS because of its neuroprotective and neuroregenerative effects. We initiated a pilot clinical study of a combination of Cerebrolysin and riluzole to assess the therapeutic benefit of Cerebrolysin as an add-on treatment on clinical signs and symptoms in outpatients with ALS. Twenty patients with a clinically definitive diagnosis of ALS were enrolled and randomly assigned in a 1:1 ratio to receive Cerebrolysin or placebo. All patients received 50 mg of riluzole PO twice daily as a standard treatment. Patients in the Cerebrolysin group received intravenous injections of 10 mL of Cerebrolysin once daily, five days a week for the first month and three days a week for the next two months. Analysis of the ALS Functional Rating Scale - revised at Month 1 (primary outcome measure), showed a significant treatment effect in favor of Cerebrolysin with a 2.3-point improvement from baseline to Month 1 compared to a 0.9-point decrease in patients on placebo (P=0.005). The effect was maintained over the three-month study period, and the beneficial effect of Cerebrolysin over placebo was also evident in the secondary outcome measures. The safety analysis showed that the combination of riluzole and Cerebrolyisn was well tolerated. Our results demonstrate for the first time a significant clinical effect of Cerebrolysin in improving functional outcomes in patients with ALS and suggest that Cerebrolysin has potential as a novel therapeutic option for ALS.

Addiction in the time of COVID-19: Longitudinal course of substance use, psychological distress, and loneliness among a transnational Tyrolean sample with substance use disorders.

Introduction: Next to an increased use of alcohol, the current pandemic has been associated with increased psychological distress among the general population. Research on its effects on individuals suffering from substance use disorders (SUD) is scarce. This study aimed at expanding the existing literature on this topic with a focus on the impact of loneliness and perceived social support. Methods: Sixty-eight people diagnosed with SUD according to ICD-10 from the Austrian state of Tyrol and from the Italian Province of South Tyrol who had been treated in a psychiatric hospital in 2019 and one hundred and thirty-six matched reference subjects of the same regional background participated in an online survey. Sociodemographic variables and scores on the Brief Symptom Checklist, the Three-Item Loneliness Scale, and the Multidimensional Scale of Perceived Social Support were collected at baseline and 5 months thereafter. Baseline took place after the first wave, while follow-up largely coincided with the second wave of the pandemic. Results: Among both patients and the matched reference group, substance use as a means to feel better facing the pandemic rose and predicted higher levels of psychological distress. Patients were less likely to receive specific care at follow-up than at baseline and presented with a significantly higher prevalence of clinically relevant psychological distress and loneliness than the matched reference group at both assessment times. Among both groups, psychological burden remained unchanged over time. Perceived social support was generally significantly higher in the matched reference group than in patients. Loneliness and, to a lesser degree, low perceived social support predicted psychological distress. Conclusion: These findings emphasize the need of preventive and educational measures regarding substance use behavior for both individuals suffering from SUD and those without mental health disorders.

Tryptophan-kynurenine metabolism during acute alcohol withdrawal in patients with alcohol use disorder: The role of immune activation.

BACKGROUND: Recent research has suggested that excessive alcohol consumption in patients with alcohol use disorder (AUD) is associated with chronic immune activation, which affects the metabolism of the neurotransmitter precursor amino acid tryptophan (TRP) and contributes to the complex pathophysiology of AUD. Our study investigated possible immune-associated alterations of TRP to kynurenine (KYN) metabolism in patients with AUD during acute alcohol withdrawal. METHODS: We measured serum concentrations of TRP, KYN, quinolinic (QUIN), kynurenic acid (KYNA), and the immune activation marker neopterin (NEO) at the first, fifth and 10th day of alcohol withdrawal in patients with AUD, who attended a standardized in-patient treatment program and underwent a detailed clinical assessment. RESULTS: Data from these individuals were compared to data from a reference control group (RCG). The primary outcome measures were the differences in serum concentrations of metabolites between AUD patients and RCG and correlations between NEO and metabolites of the tryptophan-kynurenine pathway. r = 0.695, p < 0.001) in the AUD group. Mixed models analysis showed that NEO concentrations were positively associated with QUIN but not with KYNA concentrations. Several behavioral symptoms correlated positively with QUIN concentrations and negatively with the KYNA/QUIN ratio. CONCLUSIONS: Our findings demonstrate that the changes in TRP catabolism in acute alcohol withdrawal resulting in increased KYN production could reflect the involvement of immune-associated activation of the enzyme indoleamine 2,3-dioxygenase, as NEO concentrations correlated with the KYN/TRP ratio. In addition, our data show that this low-grade immune activation may cause an imbalance in the production of neurotoxic and neuroprotective kynurenine metabolites in AUD.