Potential Prion Involvement in Long COVID-19 Neuropathology, Including Behavior.

Prion' is a term used to describe a protein infectious particle responsible for several neurodegenerative diseases in mammals, e.g., Creutzfeldt-Jakob disease. The novelty is that it is protein based infectious agent not involving a nucleic acid genome as found in viruses and bacteria. Prion disorders exhibit, in part, incubation periods, neuronal loss, and induce abnormal folding of specific normal cellular proteins due to enhancing reactive oxygen species associated with mitochondria energy metabolism. These agents may also induce memory, personality and movement abnormalities as well as depression, confusion and disorientation. Interestingly, some of these behavioral changes also occur in COVID-19 and mechanistically include mitochondrial damage caused by SARS-CoV-2 and subsequenct production of reactive oxygen species. Taken together, we surmise, in part, long COVID may involve the induction of spontaneous prion emergence, especially in individuals susceptible to its origin may thus explain some of its manesfestions post-acute viral infection.

Associations of neuroinflammatory IL-6 and IL-8 with brain atrophy, memory decline, and core AD biomarkers - in cognitively unimpaired older adults.

Concentrations of pro-inflammatory cytokines -interleukin-6 (IL-6) and interleukin-8 (IL-8) - are increased with age and in Alzheimer's disease (AD). It is not clear whether concentrations of IL-6 and IL-8 in the central nervous system predict later brain and cognitive changes over time nor whether this relationship is mediated by core AD biomarkers. Here, 219 cognitively healthy older adults (62-91 years), with baseline cerebrospinal fluid (CSF) measures of IL-6 and IL-8 were followed over time - up to 9 years - with assessments that included cognitive function, structural magnetic resonance imaging, and CSF measurements of phosphorylated tau (p-tau) and amyloid-ß (Aß-42) concentrations (for a subsample). Higher baseline CSF IL-8 was associated with better memory performance over time in the context of lower levels of CSF p-tau and p-tau/Aß-42 ratio. Higher CSF IL-6 was related to less CSF p-tau changes over time. The results are in line with the hypothesis suggesting that an up-regulation of IL-6 and IL-8 in the brain may play a neuroprotective role in cognitively healthy older adults with lower load of AD pathology.

A Review Article on Exercise Intolerance in Long COVID: Unmasking the Causes and Optimizing Treatment Strategies.

There is a growing body of research on SARS-CoV-2 (PASC), previously known as the post-COVID syndrome, a chronic condition characterized by symptoms that persist after SARS-CoV-2 infection. Among these symptoms, feelings of physical exhaustion and prolonged fatigue are particularly prevalent and can significantly impact patients' quality of life. These symptoms are associated with reduced overall physical capacity, decreased daily physical activity, malaise after intense training, and intolerance to physical activity (IFA). IFA, described as a reduced ability to perform physical activities typical for the patient's age, can often lead to a sedentary lifestyle. Prolonged physical inactivity can cause deterioration in the overall physical condition and disrupt mitochondrial function, triggering a vicious cycle of gradual symptom worsening. The underlying causes of PASC remain unclear; however, several biochemical mechanisms have been discussed to explain the body's energy depletion, and a multidisciplinary approach that combines physical and cognitive rehabilitation and lifestyle interventions such as exercise and diet modifications has been suggested to improve the overall health and well-being of PASC patients. This critical review aims to review the existing research on the possible causes and links among chronic fatigue, reduced physical activity, and exercise intolerance in patients with PASC. Further research into the underlying causes and treatment of PASC and the importance of developing individualized treatment is needed to address each patient's unique health requirements.

The Updating and Individualizing of Sleep Hygiene Rules for Non-clinical Adult Populations.

Sleep hygiene is essential for the prevention of somatic and mental disorders, including the prevention of sleep disorders. However, it does not typically address individual differences. The aim of this review is threefold: first, to outline the empirical evidence for particular components of sleep hygiene rules; second, to indicate the importance of individualized sleep hygiene application with regard to the varying degree of validity of sleep hygiene rules in the population; third, to highlight a new field of sleep hygiene, namely light hygiene. PubMed and Google Scholar were used to identify studies that were published between 2007 and 2022. A search was conducted for studies related to sleeping rules topics: sleep regularity, regular exercise, alcohol, caffeine, napping, relaxation and meditation, food intake and light exposure. In applying these sleep hygiene principles, it is essential to pay attention to individual variables such as age, genetic predisposition, health status, and substance (caffeine, alcohol) possible dependence.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Time Perception in Adults: Do Adults with Different ADHD Symptomatology Severity Perceive Time Differently? Findings from the National Czech Study.

BACKGROUND Studies show neurological differences between patients with attention-deficit/hyperactivity disorder (ADHD) and healthy controls. Furthermore, it is possible that poor timing is linked with impairments in neural circuitry. This study aimed to test the hypothesis that there is a difference in time perception between adults with severe ADHD symptomatology and adults with no ADHD symptomatology. MATERIAL AND METHODS Previously, we collected data from a more extensive set of participants (n=1518) concerning the prevalence of ADHD in adulthood. We recruited participants from 3 groups defined by increasing ADHD severity out of this participant pool. Each participant was presented with 2 experimental tasks (in counterbalanced order): duration estimation and duration discrimination. RESULTS In general, we did not find any specific differences in time perception related to the severity of ADHD. Regarding duration estimation, we found that the difference between the actual and estimated durations increased with the actual duration (F(1, 7028.00)=2685.38, P<0.001). Although the differences between groups were not significant, the group×duration interaction was (F[1, 7028.00]=10.86, P<0.001), with a very small effect size (ηp²<0.001, 95% CI [0.00, 0.01]). CONCLUSIONS The results suggest that although individuals may demonstrate increased ADHD symptomatology, they may not have objectively more significant difficulties in time perception tasks than their counterparts with mild symptomatology. Nonetheless, time perception should be further studied because, as qualitative research suggests, participants with more severe ADHD symptomatology subjectively perceive more significant differences in time management in real life.

Cognitive and Socioemotional Development at 5 and 9 Years of Age of Children Born with Very Low Birth Weight and Extremely Low Birth Weight in the Czech Republic.

BACKGROUND There is a high prevalence of cognitive and socioemotional dysfunction in very low birth weight (VLBW <1500 g) and extremely low birth weight (ELBW <1000 g) children. This study from the Czech Republic aimed to compare the cognitive and socioemotional development at 5 and 9 years of age of children born with VLBW/ELBW with children born with normal birth weight (NBW ≥2500 g). MATERIAL AND METHODS The clinical group consisted of 118 VLBW/ELBW children and the control group consisted of 101 children with NBW at ages 5 to 9 years. The research battery included selected subscales from the Intelligence and Development Scales (IDS), A Developmental Neuropsychological Assessment - second edition (NEPSY-II), and the Behavior Rating Inventory of Executive Function (BRIEF). Data were analyzed using STATA IC v. 15 software and G*Power (descriptive statistic, analysis of variance (ANOVA), correlations, multivariate analysis of variance - MANOVA, post hoc power analysis). RESULTS We found a statistically significant difference in cognitive and socioemotional development between children with VLBW/ELBW and those with NBW. The average intelligence quotient (IQ) of VLBW/ELBW children was 96.38, while that of NBW children was 12.98 points higher (P<0.001). NBW children achieved better results on all subtests of the IDS (P<0.001) as well as in affect recognition (P<0.001). All results for both groups were within normal range. Parents of VLBW/ELBW children did not recognize impaired executive functioning (P=0.494). CONCLUSIONS This study has shown significant cognitive and socioemotional deficit in children born with VLBW and ELBW when evaluated at 5 and 9 years of age.

A Real-World Study on the Use of the Alcohol Use Disorders Identification Test (AUDIT) in Men Admitted to a Psychiatric Hospital.

BACKGROUND This real-world study aimed to investigate the use of the Alcohol Use Disorders Identification Test (AUDIT) in men admitted to a psychiatric hospital. MATERIAL AND METHODS The AUDIT questionnaire (10 items) was consecutively administered for a period of 3 years to male patients admitted to a psychiatric hospital (n=636). Laboratory blood tests of biochemical parameters were measured as biomarkers of alcohol consumption. Data were evaluated using linear models with mixed effects in the case of continuous dependent variables and logistic regression models with mixed effects in the case of categorical dependent variables. RESULTS We found that 45.3% of the patients had a high risk of alcohol consumption or alcohol dependence and 54.7% had a low risk of alcohol consumption. The ICD-10 diagnoses of alcohol-related disorders (F1x), psychotic disorders (F2x), affective disorders (F3x), neurotic and psychosomatic disorders (F4x) were statistically significantly associated with total AUDIT score (P<0.001). There was a statistically significant association between the total AUDIT score and length of hospitalization (P=0.004) and the incidence of suicidal thoughts (P=0.003). Plasma concentrations of alanine aminotransferase (P=0.005), aspartate aminotransferase (P<0.001), gamma glutamyltransferase (P=0.001), total cholesterol (P=0.027) and mean corpuscular value of erythrocytes (P<0.001) were statistically significantly increased with a higher AUDIT score. CONCLUSIONS This real-world study showed that the AUDIT questionnaire evaluated the severity of disorders caused by alcohol and their impact on comorbid mental disorders. These results may be helpful in improving targeted interventions in this group of patients.

A Prospective Single-Center Study of the Effects of Repetitive Transcranial Magnetic Stimulation at 2-Week Follow-Up in 17 Patients with Chronic Orofacial Pain Diagnosed by Infrared Thermography.

BACKGROUND Infrared thermography is a diagnostic method used to monitor acute and chronic orofacial pain syndrome. Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive brain stimulation. This prospective study from a single center aimed to investigate the effects of rTMS and used infrared thermography as a confirmatory test of orofacial pain. MATERIAL AND METHODS We used infrared thermography to examine the incidence of inflammatory changes as orofacial pain triggers. During the analysis of rTMS effects on patients with orofacial pain, we compared the decrease in pain and the thermal difference in the study group (n=17) and in the research group (n=13). RESULTS In the control group (n=13), there were no statistically significant changes. Both groups showed a significant decrease in self-reported pain. Numerical pain rating scores were significantly lower after S2 stimulation than after S1/M1 (P=0.0071) or sham (P=0.0187) stimulation. The Brief Pain Inventory scores were also lower 3 to 5 days after S2 stimulation than at the pretreatment baseline (P=0.0127 for the intensity of pain and p=0.0074 for the interference of pain), and after S1/M1 (P=0.001 and P=0.0001) and sham (P=0.0491 and P=0.0359) stimulations. CONCLUSIONS The findings from this study support the role of infrared thermography for the diagnosis of chronic orofacial pain, and showed that on the first and fifth days of rTMS therapy in the study group there was a significant reduction of the thermography findings when compared with the control group without rTMS therapy.

Unusual Set of Adverse Effects During Right-Unilateral Ultrabrief Electroconvulsive Therapy Led to the Discovery of a Brain Tumor: A Case Report.

We describe a case of a right-handed, 42-year-old, Caucasian female patient who manifested a set of unusual adverse effects during maintenance ultrabrief right-unilateral electroconvulsive therapy (ECT)-generalized myoclonic secondary seizure with lateralization nonresponsive to repeated intravenous diazepam application, deviation of the tongue and the head to the left, ping-pong gaze with nystagmoid jerks, postictal hypoactive confusion state lasting 15 minutes (with a total time to recovery 30 minutes), and likely Todd's paralysis after the procedure (subsided within 24 hours). These adverse effects led to a thorough clinical investigation and eventually the discovery of a brain tumor. In the article, we hypothesize about the possible interaction between the intracranial mass and ECT and provide a literature overview on the topic. Cases like this are likely underreported, and although several studies demonstrate that ECT can be applied safely to patients with an intracranial mass, this report demonstrates that brain tumor can interfere with ECT in an unpredictable way and have severe consequences (eg, unresponsiveness to diazepam when attempting to halt the seizure as our patient). Unusual symptoms after ECT, albeit reversible, such as in this case report, should be followed by a thorough neurological check-up to exclude any underlying organic pathology.

Neuroinflammation and Tau Interact with Amyloid in Predicting Sleep Problems in Aging Independently of Atrophy.

Sleep problems relate to brain changes in aging and disease, but the mechanisms are unknown. Studies suggest a relationship between ß-amyloid (Aß) accumulation and sleep, which is likely augmented by interactions with multiple variables. Here, we tested how different cerebrospinal fluid (CSF) biomarkers for brain pathophysiology, brain atrophy, memory function, and depressive symptoms predicted self-reported sleep patterns in 91 cognitively healthy older adults over a 3-year period. The results showed that CSF levels of total- and phosphorylated (P) tau, and YKL-40-a marker of neuroinflammation/astroglial activation-predicted poor sleep in Aß positive older adults. Interestingly, although brain atrophy was strongly predictive of poor sleep, the relationships between CSF biomarkers and sleep were completely independent of atrophy. A joint analysis showed that unique variance in sleep was explained by P-tau and the P-tau × Aß interaction, memory function, depressive symptoms, and brain atrophy. The results demonstrate that sleep relates to a range of different pathophysiological processes, underscoring the importance of understanding its impact on neurocognitive changes in aging and people with increased risk of Alzheimer's disease.

Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment of Depression and Anxiety in a Patient with Anorexia Nervosa.

Anorexia nervosa (AN) is characterized by restricted eating, emaciation, and distorted body image and tends to be a chronic and deadly disorder with a high risk of developing a relapsing course described as a severe and enduring anorexia. This case study reports a patient with AN with comorbid depression and anxiety who was treated by repetitive transcranial magnetic stimulation (rTMS). Our patient's first hospitalization in our ED clinic was at the age of 25 in 2012. Her anorexia symptoms have been developing over 1.5 years. The body mass index (BMI) at admission was 12.21 kg/m². She was stimulated by use of a MAGSTIM Super Rapid 2 device, every Monday through Friday (5 days a week) with the frequency 10 Hz, 15 trains/day, 100 pulses/train, intertrain interval 107 s for 10 days. The specific spot of stimulation was over the left DLPFC. The therapy was evaluated, both by the team and by the patient, as ineffective. Shortly after the therapy was finished, the patient was discharged with final weight of 46 kg and BMI 13.15 kg/m². We showed, that despite our positive clinical experiences with rTMS therapy in depression and anxiety, the treatment of AN and comorbid depressive disorder with anxious distress, our patient's anorexic, anxious, and depressive symptoms remained unaffected. In this case, only invasive medical intervention helped the patient to reach normal weight, but without any significant changes in her psychology. This case study shows the need for further investigation of the influence that body weight might have and whether the number of sessions has an effect on rTMS efficacy.

[Suicide a serious health and social problem with the possibility of prevention]. / Sebevrazednost závazný zdravotne-spolecenský problém s mozností prevence.

Suicide is a serious health and social problem whose incidence varies between genders, age groups, geographical distribution and with influence of socio-political structure of society. It has been identified many risk factors and this behavior has etiological heterogeneity. There is no effective algorithm to predict suicidal activity in clinical practice, but increase the detection is associated with introducing the professional community and especially primary care physicians with clinical, psychological, sociological and biological factors whose can bring increasing of the recognition of vulnerable individuals and allow initiation of therapeutic interventions psychotherapy, psychopharmacology, neuromodulatory modalities or their combinations to achieve effective level of suicide prevention.

Aging Brain from a Lifespan Perspective.

Research during the last two decades has shown that the brain undergoes continuous changes throughout life, with substantial heterogeneity in age trajectories between regions. Especially, temporal and prefrontal cortices show large changes, and these correlate modestly with changes in the corresponding cognitive abilities such as episodic memory and executive function. Changes seen in normal aging overlap with changes seen in neurodegenerative conditions such as Alzheimer's disease; differences between what reflects normal aging vs. a disease-related change are often blurry. This calls for a dimensional view on cognitive decline in aging, where clear-cut distinctions between normality and pathology cannot be always drawn. Although much progress has been made in describing typical patterns of age-related changes in the brain, identifying risk and protective factors, and mapping cognitive correlates, there are still limits to our knowledge that should be addressed by future research. We need more longitudinal studies following the same participants over longer time intervals with cognitive testing and brain imaging, and an increased focus on the representativeness vs. selection bias in neuroimaging research of aging.

Markers of predicting discharge from forensic psychiatric hospitals in Czechia.

BACKGROUND: Secure forensic hospital treatments are resource-intensive, aiming to rehabilitate offenders and enhance public safety. While these treatments consume significant portions of mental health budgets and show efficacy in some countries, their effectiveness in Czechia remains underexplored. Previous research has highlighted various factors influencing the likelihood of discharge from these institutions. Notably, the role of sociodemographic variables and the length of stay (LoS) in the context of forensic treatments has presented inconsistent findings across studies. METHODS: The study, part of the 'Deinstitutionalization project' in Czechia, collected data from all inpatient forensic care hospitals. A total of 793 patients (711 male, 79 female and 3 unknown) were included. Data collection spanned 6 months, with tools like HoNOS, HoNOS-Secure, MOAS, HCR-20V3 and AQoL-8D employed to assess various aspects of patient health, behaviour, risk and quality of life. RESULTS: The study revealed several determinants influencing patient discharge from forensic hospitals. Key assessment tools, such as HoNOS secure scores and the HCR-20 clinical subscale, showed that higher scores equated to lower chances of release. Furthermore, specific diagnoses like substance use disorder increased discharge odds, while a mental retardation diagnosis significantly reduced it. The type of index offense showed no influence on discharge decisions. CONCLUSION: Factors like reduced risk behaviours, absence of mental retardation diagnosis, social support and secure post-release housing plans played significant roles. The results underscored the importance of using standardized assessment tools over clinical judgement. A standout insight was the unique challenges faced by patients diagnosed with mental retardation, emphasizing a need for specialized care units or tailored programmes.

Differences in early life cognitive function explain the association between low education and early dementia risk.

Major initiatives are currently attempting to prevent dementia by targeting modifiable risk factors. Low education is frequently pointed to as a potential key factor, due to its robust relationship with dementia risk. Impact of education is notoriously difficult to assess, however, because of associations with multiple other risk and protective factors, and large population-representative samples are required to tease the relationships apart. Here, we studied 207,814 Norwegian men born between 1950 and 1959 who underwent compulsory cognitive testing during military conscription as young adults, to systematically test associations of education, cognition, and other potentially important factors. While low education was associated with increased risk for dementia diagnosis (Hazard ratio [HR] = 1.37, CI: 1.17-1.60), this association was fully explained by earlier cognitive test scores (HR = 1.08, CI: .91-1.28). In contrast, low cognitive score was associated with double risk of later dementia diagnosis, even when taking education into account (HR = 2.00, CI: 1.65-2.42). This relationship survived controlling for early-life socioeconomic status and was replicated within pairs of brothers. The latter finding suggests that genetic and environmental factors shared within families, such as common genetics, parental education, childhood socioeconomic status, or other shared experiences, cannot account for the association. Rather, independent, non-familial factors are more important. In contrast, within-family factors accounted for the relationship between low education and diagnosis risk. In conclusion, implementing measures to increase cognitive function in childhood and adolescence appears to be a more promising strategy for reducing dementia burden.

Subtypes of brain change in aging and their associations with cognition and Alzheimer's disease biomarkers.

Structural brain changes underly cognitive changes in older age and contribute to inter-individual variability in cognition. Here, we assessed how changes in cortical thickness, surface area, and subcortical volume, are related to cognitive change in cognitively unimpaired older adults using structural magnetic resonance imaging (MRI) data-driven clustering. Specifically, we tested (1) which brain structural changes over time predict cognitive change in older age (2) whether these are associated with core cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers phosphorylated tau (p-tau) and amyloid-ß (Aß42), and (3) the degree of overlap between clusters derived from different structural features. In total 1899 cognitively healthy older adults (50 - 93 years) were followed up to 16 years with neuropsychological and structural MRI assessments, a subsample of which (n = 612) had CSF p-tau and Aß42 measurements. We applied Monte-Carlo Reference-based Consensus clustering to identify subgroups of older adults based on structural brain change patterns over time. Four clusters for each brain feature were identified, representing the degree of longitudinal brain decline. Each brain feature provided a unique contribution to brain aging as clusters were largely independent across modalities. Cognitive change and baseline cognition were best predicted by cortical area change, whereas higher levels of p-tau and Aß42 were associated with changes in subcortical volume. These results provide insights into the link between changes in brain morphology and cognition, which may translate to a better understanding of different aging trajectories.

Fetal influence on the human brain through the lifespan.

Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates consistently to lifespan brain characteristics and changes, and to what extent these influences are of a genetic or environmental nature. Here we show remarkably stable and lifelong positive associations between BW and cortical surface area and volume across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4-82 y of age, w/386 monozygotic twins, followed for up to 8.3 y w/12,088 brain MRIs). In contrast, no consistent effect of BW on brain changes was observed. Partly environmental effects were indicated by analysis of twin BW discordance. In conclusion, the influence of prenatal growth on cortical topography is stable and reliable through the lifespan. This early-life factor appears to influence the brain by association of brain reserve, rather than brain maintenance. Thus, fetal influences appear omnipresent in the spacetime of the human brain throughout the human lifespan. Optimizing fetal growth may increase brain reserve for life, also in aging.

Tobacco treatment outcomes in patients with and without a history of depression, Czech Republic, 2005-2010.

INTRODUCTION: Higher prevalence of smoking among depressed patients, as well as the risk of depression in smokers, is well documented. The proportion of patients with a history of depression among those seeking intensive treatment of tobacco dependence is also high. In contrast, evidence of treatment success in this subgroup of patients is controversial. The aim of this study was to compare smoking abstinence rates after tobacco treatment in smokers with and without a history of depression. METHODS: We reviewed retrospective data from 1,730 smokers seeking treatment in Prague, Czech Republic. History of depression was defined as past diagnosis of depression or current treatment of depression. After a 1-year, self-reported smoking status was validated by expired-air carbon monoxide. We used logistic regression to analyze associations between abstinence rates, history of depression, and other factors (eg, age, sex, tobacco dependence). RESULTS: Of 1,730 smokers treated, 289 (16.7%) had a history of depression. The smoking abstinence rate at 1 year was 32.5% for smokers with a history of depression and 38.7% for those with no history (P = .048). Among women, abstinence did not differ between groups (35.0% vs 35.7%; P = .86). However, among men, those with a history of depression had lower rates of abstinence (27.4% vs 41.3%; P = .009). After adjustment for baseline covariates, history of depression was not significantly associated with smoking abstinence in men or women. CONCLUSION: Intensive outpatient tobacco treatment programs can achieve abstinence rates among smokers with a history of depression similar to rates among the general population.

Childhood School Performance in Adults Diagnosed with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Children with ADHD often tend to underperform in school. This partial study aimed to find out if the school experience of adults with higher ADHD symptomatology differs from those with lower and no ADHD symptomatology. METHOD: Based on the results of ASRS questionnaires, the respondents were divided into three groups (low, medium, and high) according to the manifested ADHD symptomatology. We explored their school experiences by looking at their grades for behavior at school, notes regarding their attendance, school expulsion, and other school experiences. RESULTS: Children with higher ADHD symptomatology were significantly more likely to be expelled, receive notes for bad behavior, disturbing or forgetting as well as receive reprimands from teachers. CONCLUSION: Our results show that children with increased ADHD symptomatology experience more difficulties with school behavior, they are frequently reprimanded, and they do receive more negative feedback regarding their attendance and tardiness from teachers.