Physical Exercise Prevents the Cognitive Decline among Older Adults in Romania.

Cognitive decline is one of the most important challenges related to the aging process, due to its important impact on individuals. Several studies have reported that physical exercise with a specific intensity and frequency is beneficial for maintaining cognitive health in the ageing population. The present study investigated the impact of general physical exercise on cognitive health in the older population in Romania. The study involved 60 individuals (60% male, 40% female), with a mean age of 60.78 years (SD = 2.97). The Health Interview Survey and The Minnesota Heart Survey assessed exercise frequency and intensity, while the Montreal Cognitive Assessment (MoCA) determined mild cognitive impairment (MCI) levels. The results of the statistical analysis showed that high-intensity physical exercise at a frequency of three to four times a week at the age of 40-50 years is recommended in order to significantly reduce cognitive decline. In addition, for the age of 60 years old, the results established that engaging in physical activities of a moderate intensity with a frequency of 2-3 times per month is sufficient to maintain healthy cognition. The findings suggest that exercise can serve as a behavioral intervention to mitigate cognitive dysfunction and complement past research on its cognitive health advantages.

Investigating the Impact of Nutrition and Oxidative Stress on Attention Deficit Hyperactivity Disorder.

Background/Objectives: Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder, characterized by difficulty maintaining attention, impulsivity, and hyperactivity. While the cause of this disorder is still unclear, recent studies have stated that heredity is important in the development of ADHD. This is linked to a few comorbidities, including depression, criminal behavior, and anxiety. Although genetic factors influence ADHD symptoms, there are also non-genetic factors, one of which is oxidative stress (OS), which plays a role in the pathogenesis and symptoms of ADHD. This review aims to explore the role of OS in ADHD and its connection to antioxidant enzyme levels, as well as the gut-brain axis (GBA), focusing on diet and its influence on ADHD symptoms, particularly in adults with comorbid conditions. Methods: The literature search included the main available databases (e.g., Science Direct, PubMed, and Google Scholar). Articles in the English language were taken into consideration and our screening was conducted based on several words such as "ADHD", "oxidative stress", "diet", "gut-brain axis", and "gut microbiota." The review focused on studies examining the link between oxidative stress and ADHD, the role of the gut-brain axis, and the potential impact of dietary interventions. Results: Oxidative stress plays a critical role in the development and manifestation of ADHD symptoms. Studies have shown that individuals with ADHD exhibit reduced levels of key antioxidant enzymes, including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), as well as a diminished total antioxidant status (TOS) compared to healthy controls. Additionally, there is evidence of a close bidirectional interaction between the nervous system and gut microbiota, mediated by the gut-brain axis. This relationship suggests that dietary interventions targeting gut health may influence ADHD symptoms and related comorbidities. Conclusions: Oxidative stress and the gut-brain axis are key factors in the pathogenesis of ADHD, particularly in adults with comorbid conditions. A better understanding of these mechanisms could lead to more targeted treatments, including dietary interventions, to mitigate ADHD symptoms. Further research is required to explore the therapeutic potential of modulating oxidative stress and gut microbiota in the management of ADHD.

Neuropathological findings in essential tremor.

Essential tremor (ET) is one of the most common neurological conditions and the most common movement disorder. The pathophysiological mechanisms that underlie this entity have not yet been described. However, recent post-mortem brain studies have provided useful insight into the underlying pathology of ET. Two brain areas have been consistently found to present neuropathological alterations in patients with ET: the brainstem, for presence of Lewy bodies or neuronal depletion, and the cerebellum, regarding Purkinje cells' morphology and density. In the present study we aim to review the literature on the main neuropathological findings in ET brains.

Oral Health and "Modern" Digestive Diseases: Pathophysiologic and Etiologic Factors.

In the contemporary era of medicine, exploring the complexity of the human body and its intricate interactions has become a central concern for health researchers. The main purpose of this article is to summarize the current understanding of relevant pathophysiological factors such as chronic inflammation, dysbiosis (microbial imbalance), and metabolic disorders, as well as etiological factors including dietary habits, lifestyle choices, obesity, metabolic syndrome, and genetic predispositions, as well as to emphasize potential avenues for upcoming studies and their medical significance. Additionally, this article aims to assess the potential impact of integrated treatment approaches on patient outcomes, emphasizing the need for interdisciplinary collaboration between gastroenterologists, dentists, and other healthcare professionals to develop comprehensive care plans that address both oral and digestive health issues simultaneously. Among the branches with a significant impact on general well-being are oral cavity health and digestive diseases, which have been the subject of intensive research in recent decades. In this context, analysis of the current state of knowledge on oral cavity disorders in relation to "modern" digestive diseases such as non-alcoholic fatty liver disease (NAFLD), small intestinal bacterial overgrowth (SIBO), inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS) becomes essential for a deeper understanding of the interconnections between oral and digestive health. The temporal overlap or succession, whether preceding or following, of oral manifestations and digestive disorders should be taken seriously by both gastroenterologists and dentists to facilitate early diagnosis and explain to patients the correlation between these two body systems. In summary, this article underscores the importance of understanding the intricate relationship between oral and digestive health, advocating for interdisciplinary approaches to improve patient outcomes and guide future research.

Exploring Symptom Overlaps: Post-COVID-19 Neurological Syndrome and Post-Concussion Syndrome in Athletes.

The COVID-19 pandemic has introduced new challenges in managing neurological conditions, particularly among athletes. This paper explores the intersection of post-COVID-19 neurological syndrome (PCNS/PASC) and post-concussion syndrome (PCS), focusing on their implications in sports medicine. Our analysis covers the symptomatology, pathophysiology, and management strategies for PCNS/PASC and PPCS, with special attention paid to the unique challenges faced by athletes recovering from these conditions, including the risk of symptom exacerbation and prolonged recovery. Key findings reveal that both PCNS/PASC and PPCS present with overlapping symptoms such as cognitive difficulties, exercise intolerance, and mental health issues, but differ in specific manifestations like anosmia and ageusia, unique to COVID-19. Pathophysiological analysis reveals similarities in blood-brain barrier disruption (BBB) but differences in the extent of immune activation. Management strategies emphasize a gradual increase in physical activity, close symptom monitoring, and psychological support, with a tailored approach for athletes. Specific interventions include progressive aerobic exercises, resistance training, and cognitive rehabilitation. Furthermore, our study highlights the importance of integrating neurology, psychiatry, physical therapy, and sports medicine to develop comprehensive care strategies. Our findings underscore the dual challenge of COVID-19 and concussion in athletes, necessitating a nuanced, interdisciplinary approach to effective management. Future research should focus on the long-term neurological effects of both conditions and optimizing treatment protocols to improve patient outcomes. This comprehensive understanding is crucial for advancing the management of athletes affected by these overlapping conditions and ensuring their safe return to sports.

Patients' and caregivers' attitudes towards patient assisted suicide or euthanasia in amyotrophic lateral sclerosis-a meta-analysis.

Assisted suicide and euthanasia are long debated topics in amyotrophic lateral sclerosis (ALS) patients care. We conducted a meta-analysis to evaluate the attitudes of ALS patients and their caregivers toward physician-assisted suicide (PAS) and euthanasia. Also, we were interested to identify the factors associated with the positive or negative attitude of patients and caregivers towards PAS/euthanasia. A thorough search of the online databases (PubMed, Cochrane Library, and Web of Science) was conducted and eligibility criteria according to the PRISMA guidelines were used to include the studies in the current meta-analysis. The assessment of the quality of the selected studies was carried out using a pre-specified set of criteria by Cochrane. The studies that were selected for this meta-analysis suggested that the expression of the wish to die is more likely correlated with depression, anxiety, hopelessness, and lack of optimism. The overall prevalence of considering PAS/euthanasia significantly varies in a dependent manner over the cultural, legal, and societal factors. In this context, we found that the opinion on this topic can be deeply personal and may vary widely among individuals and communities. Lower quality of life and lower religiosity were associated with a positive attitude toward PAS/euthanasia. On the other hand, patients who are more religious are less likely to choose PAS/euthanasia. Gender does not appear to play a significant role in determining attitudes towards PAS/euthanasia in ALS patients. Other factors, such as education and psychological state, could also be important. In conclusion, end-of-life decisions in ALS patients are complex and require careful consideration of individual values, beliefs, and preferences. Understanding the factors that influence a patient's attitude towards PAS/euthanasia can help healthcare providers to offer appropriate care and support for these patients and their families.

The Effect of Antipsychotics on Cognition in Schizophrenia-A Current Narrative Review.

The majority of schizophrenia-affected individuals display deficiencies in multiple cognitive domains such as attention, working memory, long-term memory, and learning, deficiencies that are stable throughout the disease. The purpose of this narrative review was to examine the effect of antipsychotics on several cognitive domains affected by schizophrenia. Methods: We searched MEDLINE, Elsevier, Scopus, and DOAJ databases for randomized controlled trials and other studies investigating the effects of typical and atypical antipsychotics on cognition in patients with schizophrenia in studies conducted in the last decade. Results: The majority of studies included in this review showed that antipsychotics (especially SGAs) have positive effects on both cognition and general psychopathology of schizophrenia. We mention that treatment with antipsychotic substances represents an ongoing effort of the researchers, who are constantly searching for the best approach to meet the mental health needs of schizophrenia patients. Conclusions: Even with those positive results, it should be noted that more studies are needed in order to fully observe the various effects of certain antipsychotic substances on cognition.

Understanding Functional Neurological Disorder: Recent Insights and Diagnostic Challenges.

Functional neurological disorder (FND), formerly called conversion disorder, is a condition characterized by neurological symptoms that lack an identifiable organic purpose. These signs, which can consist of motor, sensory, or cognitive disturbances, are not deliberately produced and often vary in severity. Its diagnosis is predicated on clinical evaluation and the exclusion of other medical or psychiatric situations. Its treatment typically involves a multidisciplinary technique addressing each of the neurological symptoms and underlying psychological factors via a mixture of medical management, psychotherapy, and supportive interventions. Recent advances in neuroimaging and a deeper exploration of its epidemiology, pathophysiology, and clinical presentation have shed new light on this disorder. This paper synthesizes the current knowledge on FND, focusing on its epidemiology and underlying mechanisms, neuroimaging insights, and the differentiation of FND from feigning or malingering. This review highlights the phenotypic heterogeneity of FND and the diagnostic challenges it presents. It also discusses the significant role of neuroimaging in unraveling the complex neural underpinnings of FND and its potential in predicting treatment response. This paper underscores the importance of a nuanced understanding of FND in informing clinical practice and guiding future research. With advancements in neuroimaging techniques and growing recognition of the disorder's multifaceted nature, the paper suggests a promising trajectory toward more effective, personalized treatment strategies and a better overall understanding of the disorder.

Oxytocin Enhances Time-Dependent Responses in the Aggressive Zebrafish (Danio rerio).

Autism spectrum disorder (ASD) has become one of the most well-known disorders encountered since early childhood among people. Nowadays, the main concerns are its high prevalence and the lack of proper therapeutic interventions. In this way, the necessity of using animal models that can mimic some of the spectrum symptoms, besides deepening the mechanisms of occurrence, is undeniable. Oxytocin (OT) is often mentioned and linked to producing social domain improvements. The goal of the present study was to determine if different time exposures to OT can trigger distinct behavioral responses in zebrafish, potentially offering insights into autism therapy. To accomplish this goal, zebrafish were exposed to the same dose of OT (33.2 ng/mL OT) for one week but with different time frames, such as: continuous exposure for seven days, fifteen minutes per day for seven days, and every two days for the same amount of time. The behavior of the fish was recorded using the EthoVision XT 11.5 software, and each trial lasted four minutes. Specific parameters for locomotor activity and aggressive behavior were measured. Overall, zebrafish exposure to OT generated several improvements in locomotor activity and aggressive behavior. Moreover, the differences in the exposure period indicated that time is an important factor, showing that continuous exposure to OT was linked with better performance than exposure to the hormone every two days. At the same time, the most variable results were observed in the case of fish exposed every day to OT. Exposure to OT could lead to certain improvements in zebrafish behavior that can be time-sensitive. Nevertheless, further work is needed in order to investigate the mechanisms of action of OT in an ASD context.

Cognitive Impairment following Mild Traumatic Brain Injury (mTBI): A Review.

Background: Mild Traumatic Brain Injury (mTBI) has been increasingly recognized as a public health concern due to its prevalence and potential to induce long-term cognitive impairment. We aimed to consolidate this observation by focusing on findings of neuropsychological assessments, neuroimaging, risk factors, and potential strategies for intervention to prevent and treat mTBI-associated cognitive impairments. Methods: A thorough search of PubMed, PsycINFO, and Embase databases was performed for studies published until 2024. Studies focusing on cognitive impairment after mTBI, with neurocognitive assessment as a primary outcome, were included. Results: We found consistent evidence of cognitive deficits, such as memory and attention impairments, and affected executive functions following mTBI. Neuroimaging studies corroborate these findings, highlighting structural and functional changes in the brain. Several risk factors for developing cognitive impairment post-mTBI were identified, including age, gender, genetics, and pre-existing mental health conditions. The efficacy of interventions, including cognitive rehabilitation and pharmaceutical treatment, varied across studies. Conclusions: Mild TBI can lead to significant long-term cognitive impairments, impacting an individual's quality of life. Further research is necessary to validate and standardize cognitive assessment tools post-mTBI, to elucidate the underlying neural mechanisms, and to optimize therapeutic interventions.

A narrative review of risk factors and predictors for poor outcome and prolonged recovery after a mild traumatic brain injury.

Mild traumatic brain injuries (mTBI) are often caused by a blow to the head or a sudden jolt resulting in a wide range of physical, cognitive, and emotional temporary symptoms. Mild TBI diagnosis can be challenging and most commonly followed by post-concussion syndrome (PCS). When the symptoms are present for more than 3 months, prolonged post-concussive syndrome (PPCS) can be suspected. This review aims to identify and summarize the current status of the knowledge regarding the risk factors and predictors of the recovery from PCS and PPCS. A comprehensive search of the main scientific databases (PubMed, Web of Science, Embase, and Cochrane Library) was performed using keywords, such as: 'prolonged post-concussion syndrome', combined with 'risk factors', 'predictors', and 'outcomes'. Multiple studies reported more than one risk factor for PPCS development following mTBIs that were generally the results of sports-related concussions and car accidents. The most prevalent risk factor associated with PPCS was the female sex. Social factors/personality traits, anxiety, mental health disorders, or other health conditions from their past medical history, the occurrence of headache/migraines during TBI recovery, somatization, physical activity, and litigation were also reported to contribute to PPCS risk. An exhaustive approach is required to mitigate the risk of PPCS and to ensure optimal recovery after concussive events. However, larger prospective cohort studies evaluating patients that were examined and treated with standardized protocols could be needed to further validate these associations and mandate the highest risk factors for delayed recovery.

A Systematic Review and Meta-Analysis of the Inflammatory Biomarkers in Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) accounts for most TBI cases, the leading cause of morbidity and mortality worldwide. Despite its high incidence, mTBI pathophysiology remains largely unknown. Recent studies have shown that the inflammatory response is activated early after mTBI and can persist for several weeks or months. However, limited evidence on the utility of inflammatory biomarkers as predictors of clinical outcomes in mTBI has been previously provided. Thus, this systematic review and meta-analysis aims to provide an overview of the current knowledge on the role of inflammation in the pathogenesis of mTBI and the potential of some inflammatory biomolecules as biomarkers of mTBI. In this regard, eight studies comprising 1184 individuals were selected. Thus, it was shown that the increase in IL-6, TNF-α, and IL-1ß plasma levels could be implicated in the development of early post-concussion symptoms. On the other hand, the persistence of the increased plasmatic concentrations of IL-10 and IL-8 for as long as six months following the brain injury event could suggest chronic inflammation leading to neuroinflammation and late or persistent symptoms. In this context, our findings showed that inflammatory biomarkers could be relevant in diagnosing or predicting recovery or long-term outcomes of mTBI.

Epidemiology, Risk Factors, and Biomarkers of Post-Traumatic Epilepsy: A Comprehensive Overview.

This paper presents an in-depth exploration of Post-Traumatic Epilepsy (PTE), a complex neurological disorder following traumatic brain injury (TBI), characterized by recurrent, unprovoked seizures. With TBI being a global health concern, understanding PTE is crucial for effective diagnosis, management, and prognosis. This study aims to provide a comprehensive overview of the epidemiology, risk factors, and emerging biomarkers of PTE, thereby informing clinical practice and guiding future research. The epidemiological aspect of the study reveals PTE as a significant contributor to acquired epilepsies, with varying incidence influenced by injury severity, age, and intracranial pathologies. The paper delves into the multifactorial nature of PTE risk factors, encompassing clinical, demographic, and genetic elements. Key insights include the association of injury severity, intracranial hemorrhages, and early seizures with increased PTE risk, and the roles of age, gender, and genetic predispositions. Advancements in neuroimaging, electroencephalography, and molecular biology are presented, highlighting their roles in identifying potential PTE biomarkers. These biomarkers, ranging from radiological signs to electroencephalography EEG patterns and molecular indicators, hold promise for enhancing PTE pathogenesis understanding, early diagnosis, and therapeutic guidance. The paper also discusses the critical roles of astrocytes and microglia in PTE, emphasizing the significance of neuroinflammation in PTE development. The insights from this review suggest potential therapeutic targets in neuroinflammation pathways. In conclusion, this paper synthesizes current knowledge in the field, emphasizing the need for continued research and a multidisciplinary approach to effectively manage PTE. Future research directions include longitudinal studies for a better understanding of TBI and PTE outcomes, and the development of targeted interventions based on individualized risk profiles. This research contributes significantly to the broader understanding of epilepsy and TBI.

A review of the personality traits in post-concussion syndrome.

INTRODUCTION: Various manifestations ranging from physical symptoms to cognitive and emotional impairments could often be seen following head concussions that lead to mild traumatic brain injury (mTBI). These symptoms are commonly comprising the post-concussion syndrome (PCS) and their resolution could be influenced by multiple factors. Personality traits have been suggested as potential risk factors for the emergence and persistence of PCS. In this study, we aimed to investigate the possible predisposition to PCS given by certain personality traits. METHODS: Prospective cohort studies, observational studies, and cross-phenotype polygenic risk score analyses were selected from the main scientific databases (PubMed/Medline, Scopus, EMBASE, Web of Science) based on multiple-step screening, using keywords (such as "personality traits", "post-concussion syndrome", "traumatic brain injury", "anxiety", "depression", "resilience", and "somatization") and inclusion/exclusion criteria (English written studies available in full text presenting relevant data on TBI patients and their personality traits; reviews, animal studies, and studies not written in English, not available in full text, or not presenting full demographical and clinical data were excluded). The investigated personality traits included emotional reserve, somatic trait anxiety, embitterment, mistrust, parental anxiety, state anxiety, trait anxiety, anxiety sensitivity, pain catastrophizing, helplessness, sports-concussion symptom load, and cognitive resilience. RESULTS: The reviewed data from 16 selected studies suggested that personality traits play an essential role in the development and persistence of PCS. Emotional reserve, cognitive resilience, and lower levels of somatic trait anxiety were associated with better outcomes in PCS. However, higher levels of anxiety sensitivity, pain catastrophizing, helplessness, and sports-concussion symptom load were associated with worse outcomes in PCS. Parental anxiety was not associated with persistent symptoms in children following concussion. Despite the statistical analysis regarding the included publications bias was low, further studies should further investigate the correlation between TBI and some personality traits, as some of the selected studies did not included healthy individuals and their psychological profiles for comparison and correlation analysis. CONCLUSION: Personality traits may help predict the development and persistence of PCS following mTBI. Understanding the personality traits roles in PCS could assist the development of targeted interventions for the prevention and treatment of PCS. Further research is needed to better understand the complex interactions between personality traits, neurobiological factors, and psychosocial factors in PCS.

The Role of Microglial Exosomes and miR-124-3p in Neuroinflammation and Neuronal Repair after Traumatic Brain Injury.

(1) Background: In this study, we aimed to explore the regulatory mechanism of miR-124-3p microglial exosomes, as they were previously reported to modulate neuroinflammation and promote neuronal repair following traumatic brain injury (TBI). (2) Methods: Studies investigating the impact of microglial exosomal miRNAs, specifically miR-124-3p, on injured neurons and brain microvascular endothelial cells (BMVECs) in the context of TBI were reviewed. (3) Results: Animal models of TBI, in vitro cell culture experiments, RNA sequencing analysis, and functional assays were employed to elucidate the mechanisms underlying the effects of miR-124-3p-loaded exosomes on neuroinflammation and neuronal repair. Anti-inflammatory M2 polarization of microglia, mTOR signaling suppression, and BMVECs-mediated autophagy were reported as the main processes contributing to neuroprotection, reduced blood-brain barrier leakage, and improved neurologic outcomes in animal models of TBI. (4) Conclusions: Microglial exosomes, particularly those carrying miR-124-3p, have emerged as promising candidates for therapeutic interventions in TBI. These exosomes exhibit neuroprotective effects, attenuate neuroinflammation, and promote neuronal repair and plasticity. However, further research is required to fully elucidate the underlying mechanisms and optimize their delivery strategies for effective treatment in human TBI cases.

Post-Traumatic Headache: A Review of Prevalence, Clinical Features, Risk Factors, and Treatment Strategies.

Post-traumatic headache (PTH) is a common and debilitating consequence of mild traumatic brain injury (mTBI) that can occur over one year after the head impact event. Thus, better understanding of the underlying pathophysiology and risk factors could facilitate early identification and management of PTH. There are several factors that could influence the reporting of PTH prevalence, including the definition of concussion and PTH. The main risk factors for PTHs include a history of migraines or headaches, female gender, younger age, greater severity of the head injury, and co-occurring psychological symptoms, such as anxiety and depression. PTH clinical profiles vary based on onset, duration, and severity: tension-type headache, migraine headaches, cervicogenic headache, occipital neuralgia, and new daily persistent headache. Pharmacological treatments often consist of analgesics and non-steroidal anti-inflammatory drugs, tricyclic antidepressants, or antiepileptic medication. Cognitive behavioral therapy, relaxation techniques, biofeedback, and physical therapy could also be used for PTH treatment. Our work highlighted the need for more rigorous studies to better describe the importance of identifying risk factors and patient-centered treatments and to evaluate the effectiveness of the existing treatment options. Clinicians should consider a multidisciplinary approach to managing PTH, including pharmacotherapy, cognitive behavioral therapy, and lifestyle changes.

Functional Overlay Model of Persistent Post-Concussion Syndrome.

Persistent post-concussion syndrome (PPCS) is a complex and debilitating condition that can develop after head concussions or mild traumatic brain injury (mTBI). PPCS is characterized by a wide range of symptoms, including headaches, dizziness, fatigue, cognitive deficits, and emotional changes, that can persist for months or even years after the initial injury. Despite extensive research, the underlying mechanisms of PPCS are still poorly understood; furthermore, there are limited resources to predict PPCS development in mTBI patients and no established treatment. Similar to PPCS, the etiology and pathogenesis of functional neurological disorders (FNDs) are not clear neither fully described. Nonspecific multifactorial interactions that were also seen in PPCS have been identified as possible predispositions for FND onset and progression. Thus, we aimed to describe a functional overlay model of PPCS that emphasizes the interplay between functional and structural factors in the development and perpetuation of PPCS symptoms. Our model suggests that the initial brain injury triggers a cascade of physiological and psychological processes that disrupt the normal functioning of the brain leading to persistent symptoms. This disruption can be compounded by pre-existing factors, such as genetics, prior injury, and psychological distress, which can increase the vulnerability to PPCS. Moreover, specific interventions, such as cognitive behavioral therapy, neurofeedback, and physical exercise can target the PPCS treatment approach. Thus, the functional overlay model of PPCS provides a new framework for understanding the complex nature of this condition and for developing more effective treatments. By identifying and targeting specific functional factors that contribute to PPCS symptoms, clinicians and researchers can improve the diagnosis, management, and ultimately, outcomes of patients with this condition.

A Review of the Most Recent Clinical and Neuropathological Criteria for Chronic Traumatic Encephalopathy.

(1) Background: Chronic traumatic encephalopathy (CTE) is a complex pathological condition characterized by neurodegeneration, as a result of repeated head traumas. Currently, the diagnosis of CTE can only be assumed postmortem. Thus, the clinical manifestations associated with CTE are referred to as traumatic encephalopathy syndrome (TES), for which diagnostic multiple sets of criteria can be used. (2) Objectives: In this study, we aimed to present and discuss the limitations of the clinical and neuropathological diagnostic criteria for TES/CTE and to suggest a diagnostic algorithm enabling a more accurate diagnostic procedure. (3) Results: The most common diagnostic criteria for TES/CTE discriminate between possible, probable, and improbable. However, several key variations between the available diagnostic criteria suggest that the diagnosis of CTE can still only be given with postmortem neurophysiological examination. Thus, a TES/CTE diagnosis during life imposes a different level of certainty. Here, we are proposing a comprehensive algorithm of diagnosis criteria for TES/CTE based on the similarities and differences between the previous criteria. (4) Conclusions: The diagnosis of TES/CTE requires a multidisciplinary approach; thorough investigation for other neurodegenerative disorders, systemic illnesses, and/or psychiatric conditions that can account for the symptoms; and also complex investigations of patient history, psychiatric assessment, and blood and cerebrospinal fluid biomarker evaluation.

Review on the Role of Salivary Biomarkers in the Diagnosis of Mild Traumatic Brain Injury and Post-Concussion Syndrome.

(1) Background: While mild traumatic brain injuries (TBIs) are a major public health issue, post-concussion syndrome (PCS) remains a controversial entity. In both cases, the clinical diagnosis is mainly based on the symptoms and brain imaging evaluation. The current molecular biomarkers were described from blood and cerebrospinal fluid (CSF), yet both fluid collection methods are invasive. Saliva could be preferred in molecular diagnosis due to its non-invasive and non-expensive methods of acquisition, transport, and samples processing. (2) Objectives: In the present study, we aimed to review the latest developments in salivary biomarkers and their potential role in diagnosing mild TBIs, and PCS. (3) Results: In TBIs and PCS, a few novel studies focusing on salivary biomarkers have emphasized their importance in diagnosis. The previous studies mainly focused on micro RNAs, and only a few on extracellular vesicles, neurofilament light chain, and S100B. (4) Conclusions: The combination between salivary biomarkers, clinical history and examination, self-reported symptoms, and cognitive/balance testing can provide a non-invasive alternative diagnostic methodology, as compared to the currently approved plasma and cerebrospinal fluid biomarkers.