Search Results (137)

Background/Objectives: Cognitive dysfunction, or “brain fog”, following COVID-19 viral infection is strongly associated with diminished work capacity which disproportionality affects working-age adults. This study examined an existing method of cognitive rehabilitation training applied to adults struggling with workplace functioning and self-efficacy due to post-COVID-19 brain fog. Methods: Nine adults with post-COVID-19 cognitive dysfunction participated in this single arm pilot trial of a severity-adaptive cognitive training program. The participants completed 45–90 h of clinician-delivered cognitive training exercises delivered remotely in 60- to 90-min sessions, two or three times per week. The primary outcome measure was overall workplace self-efficacy with subskills of perceived workplace functioning, perception of cognitive functioning, and perception of home functioning assessed through pre and post surveys and qualitative interviews. The secondary outcome was cognitive function operationalized by an IQ score administered before and after the intervention. Results: The participants achieved significant improvements in workplace self-efficacy and cognition following cognitive training. The main qualitative themes of self-reported improvements were in executive function, health and energy, daily living activities, productivity, and socioemotional functioning. A cross-case synthesis of pre-intervention struggles, and post-intervention improvements revealed subthemes at work or school in cognitive processing and comprehension, memory, executive function, fatigue, emotional distress, confidence in work or academics, and work/academic performance impairment. As a group, the mean gain in IQ score was 10.5 points. Conclusions: This study adds to the growing body of literature examining the possibility of using cognitive rehabilitation for post-COVID-19 cognitive dysfunction impacting workplace self-efficacy and work functioning. Full article

Background: Sjögren’s disease (SjD) is a chronic systemic autoimmune disorder characterized by persistent exocrine gland inflammation, possible multi-organ involvement and a marked predominance of mid-life women. Beyond dryness and fatigue, patients report mood disturbances and cognitive complaints such as “brain fog”, which affect daily functioning and quality of life. Objective: To summarize and critically synthesize the literature on depression, anxiety, cognitive function, personality traits and quality of life assessment in adults with SjD and to highlight clinically relevant gaps. Methods: We performed a narrative review (PubMed, Cochrane, Embase through June 2025) of studies on psychological outcomes, cognitive function and quality of life in adults with SjD. Results: Depression and anxiety were frequently observed: depressive symptoms were present in roughly one-third to nearly half of patients, while anxiety symptoms were reported by about one-third. Cognitive impairment (affecting memory, attention and executive function) was also frequently described, often alongside severe fatigue and sleep disturbance. Overall, quality of life was reduced in SjD, driven mainly by fatigue and emotional distress rather than by classic disease activity. Neuroimmune mechanisms (e.g., chronic systemic inflammation and cytokine signalling such as IL-6 and TNF-α) may contribute to affective and cognitive symptoms. Overall, the evidence base remains largely cross-sectional and heterogeneous. Conclusions: Psychiatric symptoms and cognitive complaints represent a substantial and clinically relevant burden in SjD. Routine screening and multidisciplinary management that includes psychological assessment and support may improve well-being, adherence and quality of life. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a high-burden, under-researched condition characterized by heterogeneous and fluctuating symptoms, including cognitive dysfunction commonly described by patients as “brain fog”. Despite growing interest in digital health technologies for symptom monitoring and personalized care, their application to the assessment and management of cognitive dysfunction in ME/CFS remains unclear. This descriptive review aimed to examine the current scientific evidence on digital approaches related to brain fog in ME/CFS. A structured literature search following PRISMA guidance was conducted to identify relevant studies. The available literature remains limited in scope and methodological maturity. During synthesizing across studies, three main functional domains of digital application become apparent: (1) digital tools for cognitive assessment, which have the strongest evidence base; (2) digital platforms for longitudinal monitoring; and (3) digitally mediated interventions or rehabilitation approaches, both of which are less well studied. Simultaneously, the findings suggest that patient-reported brain fog may represent a visible component of the broader ME/CFS disease spectrum and could serve as an early clinical indicator guiding diagnosis and management. Interpreting these symptoms within a biopsychosocial framework may facilitate understanding of the complex nature of the disease and optimize the use of digital technologies for monitoring cognitive dysfunction and supporting patient-centered care in ME/CFS. Full article

Background: Freezing of gait (FoG) is a common symptom of Parkinson’s disease, especially in its later stages of progression. Characterized by involuntary stopping during normal gait patterns, FoG greatly increases fall risk, reducing quality of life. Given the complex presentation and etiology of FoG, current treatments have proven ineffective in managing episodes. In recent years, machine learning algorithms have been leveraged to derive actionable clinical insights from biomedical datasets. As a manifestation of neuromechanical dysfunction, impending FoG episodes may be characterized through data collected by wearable devices and sensors. Objective: This scoping review evaluates the current landscape of machine and deep learning-derived biomarkers to enhance the personalized management of FoG. Methods: This scoping review was conducted using established methodological frameworks for scoping reviews and is reported in accordance using the PRISMA-ScR checklist. Three databases were queried, with screening yielding 60 studies. Results: Thirty-nine papers reported on deep learning techniques, with the most common architectures being convolutional neural networks and long short-term memory models. Conclusions: Inertial measurement units, which can be worn on various locations, may be a promising modality for practical implementation. To generate closed-loop FoG therapies, algorithms can be integrated into real-time systems like robotic exoskeletons or adaptive deep brain stimulation. Future work in generating datasets from ambulatory devices, as well as distributed computing strategies, may lead to real-time FoG management. Full article

The coronavirus disease 2019 (COVID-19) pandemic has been associated with a wide range of neurological complications, among which persistent cognitive impairment and memory deficits are increasingly recognized as key symptoms of the post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID). Although clinical and epidemiological studies have documented these symptoms across diverse patient populations, the underlying neurobiological mechanisms remain incompletely understood. Growing evidence from human studies, neuropathological analyses, and experimental models indicates that neuroimmune and inflammatory processes plays a central role in COVID-19-associated cognitive dysfunction. As the brain’s resident immune cells, microglia are vital for synaptic health, neuroplasticity, and memory, yet these processes may be compromised after SARS-CoV-2 infection. Systemic inflammation, blood–brain barrier (BBB) disruption, endothelial injury, and cytokine signaling can induce sustained microglial activation and priming, leading to inflammasome activation, complement-mediated synaptic remodeling, oxidative stress, and impaired hippocampal neurogenesis. These processes collectively disrupt neural circuits involved in learning and memory and may underlie the persistent “brain fog” reported by COVID-19 survivors. This review synthesizes clinical, biomarker, neuroimaging, and mechanistic evidence linking SARS-CoV-2 infection to microglia-mediated neuroinflammation and memory impairment. In contrast to prior reviews that broadly describe neuroinflammation in COVID-19, we integrate multidimensional evidence into a microglia-centric immunovascular framework that highlights converging pathogenic pathways underlying cognitive symptoms. We further discuss emerging biomarkers of glial activation and evaluate current and prospective therapeutic strategies targeting microglial and neuroimmune pathways. Understanding the role of microglial dysregulation in post-COVID cognitive impairment may facilitate the development of targeted interventions to mitigate long-term neurological consequences of COVID-19. Full article

Background: Post-COVID-19 cognitive impairment, commonly referred to as “brain fog,” represents a significant clinical problem, yet its underlying mechanisms remain incompletely understood. New research indicates that long-term cognitive consequences of SARS-CoV-2 infection may result from chronic immunological dysregulation and neurometabolic changes. Objective: We aimed to assess the associations between cognitive performance, cerebral glucose metabolism, and inflammatory markers in patients with COVID-19 brain fog symptoms. Methods: This study included 47 patients with post-COVID-19 cognitive complaints enrolled in the COVMENT trial. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA). Brain glucose metabolism was evaluated with FDG PET-CT, and inflammatory markers, including C-reactive protein (CRP), monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, eosinophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were measured. Correlation analyses, logistic regression, and ROC analysis were performed to explore relationships between these factors. Results: A lower score of the MoCA abstraction domain correlated significantly with lower FDG uptake in multiple brain regions, including inferior parietal lobules and precuneus. Among inflammatory markers, only PLR demonstrated significant associations with both brain metabolism and abstraction performance. Lower PLR values were associated with greater neurometabolic impairment, and PLR < 130.1 was associated with abnormal abstraction performance. Conclusions: Post-COVID-19 cognitive dysfunction can be associated with selective neurometabolic alterations in brain regions supporting abstract reasoning. PLR seems to be associated with both cognitive performance and regional brain metabolism, suggesting a potential link between chronic immune dysregulation and neurocognitive impairment in post-COVID-19. Full article

Background/Objective: Long COVID is an important cause of disability following SARS-CoV-2 infection; yet, its underlying mechanisms are not completely understood. One proposed mechanism is the long-lasting dysregulation of the immune complement system. This systematic review is the first to summarize the current evidence and evaluate the potential role of long-lasting complement activation in people with long COVID. Methods: A systematic electronic search on PubMed, MEDLINE, CINAHL, and Embase was conducted up to 15 October 2025, to identify studies investigating complement activation in people with the post-COVID-19 condition. The Newcastle–Ottawa Scale was used to evaluate the risk of bias and methodological quality. Results: Among the 247 studies initially identified, eleven met the inclusion criteria, comprising 1435 individuals (age: 48.5 years, 70% females) with long COVID and 1124 controls (age: 43.6 years, 60% females). All studies were of a high quality, with scores ranging from 7 to 8 stars (mean: 7.6 ± 0.5). The activation of the classical complement pathway was investigated in nine studies, whereas the lectin, alternative, and terminal complement pathways were each assessed in three studies. Multiple studies investigated several complement pathways. The results were heterogeneous since several markers of complement activation spanning the classical (C2, C4a, C4b, and C1s-C1INH), alternative (Ba, iC3b, and Factor D), and terminal (C5bC6, C5a, C9, and TCC) pathways were elevated, whereas other markers were not significantly different (C3, C4, and C4d) between patients with/without long COVID. In addition, markers spanning the lectin complement pathway (MBL, and MASP1-C1INH) were not significantly different between individuals with and without long COVID. Conclusions: The current evidence suggests potential long-lasting complement system dysregulation in individuals with long COVID, although the clinical significance remains controversial, due to heterogenous findings. Specific post-COVID symptom clusters, such as fatigue, dyspnea, or brain fog, have been linked to a distinct pattern of complement dysregulation. Substantial methodological heterogeneity, including differences in follow-up periods, complement markers, assessment methods, and control groups, along with the small number of available studies, underscores the need for further research to clarify the mechanisms linking complement dysregulation to long COVID. Full article

Long COVID (LC) may involve endocrine dysfunction; however, the underlying mechanism remains unclear. To examine hypothalamic–pituitary responses in patients with LC, we conducted a single-center retrospective study of patients with refractory LC referred to our University Hospital who underwent anterior pituitary stimulation tests. Between February 2021 and November 2025, 1251 patients with long COVID were evaluated, of whom 207 (19%) had relatively low random ACTH or cortisol levels. Ultimately, 16 underwent anterior pituitary stimulation tests and were included. All tests were performed in an inpatient setting without exogenous steroids. Fifteen patients (six women, mean age 35.6 years) underwent corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH) tests. All patients had mild acute COVID-19, eight had ≥2 vaccinations, and the mean interval from infection was 343 days. Frequent symptoms included fatigue (100%), insomnia (66.7%), headache (60.0%), anorexia/nausea (40.0%), and brain fog (40.0%). Mean early-morning cortisol and 24 h urinary free cortisol were 7.5 μg/dL and 41.0 μg/day, respectively. MRI showed an empty sella in one case. Peak hormonal responses were preserved (ΔACTH 247%, ΔTSH 918%, ΔPRL 820%, ΔFSH 187%, ΔLH 1150%); however, peaks were delayed beyond 60 min in ACTH (13%), LH (33%), and FSH (87%). Notably, significantly delayed elevations remained at 120 min in the responses of TSH (4.1-fold), PRL (1.8-fold), LH (9.3-fold), and FSH (2.8-fold), suggesting possible hypothalamic involvement, particularly in the gonadotropin responses. Additionally, serum IGF-I was lowered (−0.70 SD), while GH response (mean peak 35.5 ng/mL) was preserved by growth hormone-releasing peptide (GHRP)-2 stimulation. Low-dose hydrocortisone and testosterone were initiated for three patients. Although direct viral effects and secondary suppression have been proposed, our findings may suggest that, at least in part, the observed response characteristics are consistent with functional secondary hypothalamic dysfunction rather than irreversible primary injury. These findings highlight the need for objective endocrine evaluation before initiating hormone replacements. Full article

Background/Objectives: Beyond respiratory problems, COVID-19 can cause a variety of symptoms, such as neurological disorders caused by biological and psychological factors. Brain fog (BF), a post-illness cognitive impairment that many patients report, can be evaluated with reaction time (RT) testing. Response latency is measured by RT, which can be either simple (sRT) or complex (cRT). This study focuses on how COVID-19 affects cognitive function, with particular attention on RT changes, BF prevalence, and implications for daily life. Methods: The study included 599 participants from Bosnia and Herzegovina, Croatia and Serbia. RT was measured using PsyToolkit and participants completed a COVID-19-associated BF questionnaire. Participants who experienced BF after their latest COVID-19 infection rated its severity using a visual analogue scale (VAS). Additional clinical data were obtained from medical records. Results: BF was reported by 40% of participants post-COVID-19. Men reported it less frequently but found it more disruptive. RT progressively declined post-infection, reaching peak impairment at 15 weeks, following recovery, with RT normalizing by six months. Conclusions: COVID-19 is linked to temporary RT impairment, peaking at 15 weeks post-infection and resolving by six months, independent of BF presence. This study emphasizes the need for a biopsychosocial approach to BF management. Easily available RT assessments should be incorporated into routine clinical practice. Full article

Long COVID, a condition marked by persistent symptoms following COVID-19 infection, poses significant challenges in regard to clinical management. While emerging pharmacological treatments have demonstrated limited benefits in isolated studies, clinical experience and the literature suggest that low-dose naltrexone (LDN) may be a promising therapeutic option. Therefore, in this systematic review, we aim to synthesise findings from the available literature and evaluate the overall safety and efficacy of LDN as a potential treatment for long COVID. A literature search was conducted using a combination of key terms—‘COVID’, ‘COVID-19’, ‘SARS-COV-2’, and ‘Naltrexone’— and the following databases: MEDLINE, Web of Science (Clavirate), Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Cumulative Index in Nursing and Allied Health Literature (CINAHL). The methodology is available on the PROSPERO database (CRD42025630362). Screening identified five eligible articles. Four studies were included, but only two provided comparable data suitable for meta-analysis. Meta-analysis demonstrated statistically significant improvements in fatigue, brain fog, and headaches. Preliminary evidence suggests LDN has potential benefits in the treatment of long COVID, particularly with respect to fatigue, brain fog, and headaches, but more robust studies, such as randomised controlled trials, are urgently needed to confirm LDN’s safety and efficacy. Full article

Defined by the World Health Organization as a neurological disorder, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling illness, affecting millions of people worldwide. First reported in the early nineteenth century, ME/CFS is uniquely characterized by a wide array of symptoms, including fatigue, brain fog, post-exertional malaise (PEM), sleep dysfunction, and orthostatic intolerance (OI). Despite decades of extensive research, there are no effective medical treatments or simple diagnostics for ME/CFS, with an estimated 90% of patients remaining undiagnosed. The recently discovered glymphatic system, a lymphatic analog of the brain, is believed to be responsible for the removal of toxic metabolic wastes accumulated in the course of daily activities, primarily during sleep. A link between glymphatic dysfunction and some neurological disorders such as Alzheimer’s disease has already been established, raising the possibility of its involvement in ME/CFS. Accordingly, we believe the ME/CFS medical/scientific community will be interested in seriously considering GD an important contributor to its pathophysiology. If so, therapeutics that modulate glymphatic function may also benefit patients with ME/CFS. Full article

There is a subgroup of people infected with the SARS-CoV-2 virus who manifest lingering sequelae (LongC), with neurological symptoms (nLongC). We recruited 86 COVID-19 volunteers, 35 of whom were fully recovered (Cov) and 51 who had neurological symptoms (nLongC) 4–53 months after infection and compared them to 51 healthy pre-pandemic controls (HC). Thirty-five percent of nLongC individuals carried the apolipoprotein E4 (APOE4) gene, compared to 11% of Cov. Four plasma proteins, interleukin 1 beta (IL-1β), interleukin 8 (IL-8), glial fibrillary acidic protein (GFAP), and hemopexin, continued to be elevated in both Cov and nLongC compared to HC. Soluble CD14 was elevated in nLongC but not Cov. As a group, IL-1β decreased over time in Cov but not nLongC. Two of the elevated proteins, IL-8 and GFAP, correlated with age, with both Cov and nLongC showing higher levels than HC. Using a combination of four plasma proteins, along with age, body mass index, and APOE4 presence, we were able to achieve an area under the curve (AUC) of 0.81. These results suggest that SARS-CoV-2 infection causes a low-grade inflammatory process that, even months or years after infection, does not return to pre-COVID-19 levels, which may contribute to neurologic sequelae and accelerated aging. Full article

Non-coeliac wheat sensitivity (NCWS) is characterised by gastrointestinal and extra-intestinal symptoms following gluten/wheat ingestion in individuals without coeliac disease or wheat allergy but remains controversial due to symptom overlap with irritable bowel syndrome (IBS). This narrative review aims to provide a comprehensive, critical analysis of NCWS as a clinical and biological entity, examining the evidence for its distinction from related disorders. While self-reported rates are high (often >10%) in the general population, rigorous double-blind, placebo-controlled challenge (DBPCC) studies confirm the diagnosis in only a minority of cases (typically <30%). The clinical presentation is heterogeneous, combining IBS-like symptoms with systemic complaints such as “brain fog,” headaches, and fatigue. The pathophysiology is distinct from coeliac disease, involving innate immune activation, altered intestinal barrier function, and gut dysbiosis. Non-gluten wheat components, particularly fructans and amylase-trypsin inhibitors, are implicated as potential triggers. Diagnosis is challenging, requiring the exclusion of other disorders and adherence to complex dietary challenge protocols such as the Salerno Experts’ Criteria, which are impractical for routine clinical use. The search for validated biomarkers is a key research area and investigated candidates include serological markers such as IgG anti-gliadin antibodies, inflammatory markers such as faecal calprotectin, and proteins related to intestinal permeability such as zonulin, but results have been conflicting and require further validation. Management primarily involves elimination of wheat and gluten from the diet, although a low-FODMAP diet has also proven effective as an adjunctive treatment. In conclusion, NCWS is a clinical entity whose study and management are critically hampered by the absence of validated diagnostic criteria and biomarkers. Progress requires methodologically rigorous DBPCC trials to elucidate its mechanisms and develop reliable diagnostic tools. Full article

Background: Menopause is associated with metabolic, sensory, and psychosocial changes that may reshape eating behaviours and nutrition-related quality of life. This study explored how women experience nutrition and chemosensory changes during menopause and how these intersect with identity, control, and social practices. Methods: We conducted online focus groups (Microsoft Teams) with women living in Ireland (n = 40; mean age 58.3 years (±4.5 years)) between January and March 2025. Discussions followed a semi-structured guide focused on taste/smell, appetite, food choice, and coping. Sessions were recorded, transcribed, anonymised, and analysed following Braun and Clarke’s thematic analysis. Results: Four themes captured patterned meanings in the dataset: (1) Chemosensory Changes—reports of diminished taste, contrasted with heightened smell and selective intensification (sweetness), prompting compensatory behaviours (more salt/spice/strong coffee) and new aversions (e.g., cucumber, spicy dishes) alongside unexpected likes (e.g., dark chocolate); (2) Behavioural and Emotional Consequences—increased snacking, sugar/salt cravings, and perceived loss of satiety co-occurred with weight gain and altered body shape, undermining food pleasure and self-confidence; (3) Interacting Influences—affecting vasomotor symptoms, sleep disturbance, joint pain, and “brain fog” compounded dietary disruptions and social withdrawal (e.g., embarrassment about appetite, reduced desire to dine out); (4) Strategies for Wellbeing—women described medical approaches (HRT, prescribed medications) alongside food modifications and the importance of diagnosis, information, and peer/professional support. Conclusions: Menopause reshapes sensory perception and eating behaviour in complex, individualised ways that extend beyond biology to identity and social life. Nutrition care should integrate symptom management with person-centred strategies and improved access to evidence-based information, diagnosis, and support networks. Full article

Long COVID, characterized by persistent symptoms following COVID-19 infection, poses significant challenges to individuals’ well-being. This study explores the multifaceted nature of long COVID, encompassing neurological and psychological manifestations. Neurological symptoms, including difficulty thinking clearly (brain fog) and concentrating, are prominent features of long COVID, drawing increasing attention due to their potential long-term adverse impact on the patient’s daily functioning and quality of life. Furthermore, anxiety emerges as a prevalent psychological concern among individuals with long COVID, exacerbating the uncertainty and distress associated with the ongoing symptoms of the virus. Despite growing recognition of the interplay between long COVID, neurological symptoms, and anxiety, there remains a notable gap in the literature regarding the specific relationship between these domains. This study addresses this gap by investigating how the presence of long COVID symptoms relates to the manifestation of neurological symptoms, with anxiety as a potential mediator. Utilizing data from the COVID-19 Health and Mental Health Survey, this research provides insights into the complex interplay between long COVID, neurological symptoms, and anxiety. This research provides a deeper understanding of the long-term implications of this virus and informs assessment and intervention for these patients. Full article