Neurologic complications of long-COVID syndrome are one of the leading causes of global disability. In particular, post-COVID cognitive dysfunction and dysautonomia in the form of postural orthostatic tachycardia syndrome (POTS) markedly affect patient quality of life and ability to return to work. The underlying pathophysiology of postCOVID neurologic complications is unknown but is likely multifactorial with immune dysregulation and microvascular dysfunction playing central roles. Specific pathogenic factors with supportive evidence to date include cytokine-mediated inflammation, autoantibodies, immune exhaustion, disruption of the renin-angiotensin system, reduced serotonin levels and microglial activation. The prevalence of post-COVID cognitive dysfunction ranges from 10% to 88% and is affected by viral variant and hospitalization status among other factors, while that of long-COVID POTS is unknown due to referral bias and varying definitions. Treatment is largely supportive and often incorporates combined modalities. Marginal benefits with cognitive behavioral therapy, hyperbaric oxygen therapy and supplements have been shown for post-COVID brain fog, while established POTS therapies aimed at improving venous return and reducing heart rate may reduce symptoms of long-COVID POTS. Although significant recovery has been noted for many cases of post-COVID brain fog and POTS, prospective studies have demonstrated evidence of persistent symptoms and neurologic deficits a year after infection in some patients. Further studies that provide insight into the underlying pathophysiology of long-COVID are needed for development of target directed therapy.

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The chapter explores the role of neuropsychology in understanding brain fog as a subjective complaint in the context of COVID-19. It discusses the historical and medical significance of the term \"brain fog\" and its psychological and neurological aspects. The chapter identifies the cognitive domains commonly affected by brain fog, such as attention, executive function, memory, and language. Additionally, it emphasizes the impact of societal changes during the COVID-19 pandemic on the general population as a crucial backdrop for understanding the issue. The chapter also highlights the important role of clinical and research neuropsychologists in gaining clarity on grouped data and individual patients\' cognitive and emotional difficulties after COVID-19 infection. It discusses indications for neuropsychological rehabilitation and therapy and describes typical therapy phases and methods, including new approaches like telemedicine, virtual reality, and mobile app-based rehabilitation and self-tracking. The chapter underscores that experiences of brain fog can vary among COVID-19 patients and may change over time. It provides clinicians and interested parties with an in-depth understanding of brain fog and its manifestations, concomitant subtypes, and concrete strategies for addressing it. The chapter emphasizes the critical role of neuropsychology in scientifically examining brain fog and advocating for personalized approaches to cognitive rehabilitation.

A substantial number of patients develop cognitive dysfunction after contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significantly contributing to long-coronavirus disease (COVID) morbidity. Despite the urgent and overwhelming clinical need, there are currently no proven interventions to treat post-COVID cognitive dysfunction (PCCD). Psychostimulants like methylphenidate may enhance both noradrenergic and dopaminergic pathways in mesolimbic and pre-frontal areas, thus improving memory and cognition. We present a case series of six patients who were treated at the Johns Hopkins Post-Acute COVID-19 Team (PACT) clinic for PCCD with methylphenidate 5 - 20 mg in the context of routine clinical care and followed for 4 to 8 weeks. Baseline and post-treatment outcomes included subjective cognitive dysfunction and objective performance on a battery devised to measure cognitive dysfunction in long-COVID patients. Three out of the six patients reported subjective improvement with methylphenidate, one patient described it as \"notable\" and another as \"marked\" improvement in memory and concentration. We also found significant pre-treatment subjective complaints of cognitive dysfunction; however, formal cognitive assessment scores were not severely impaired. A statistically significant difference in pre and post scores, favoring intervention, was found for the following cognitive assessments: Hopkins verbal learning test (HVLT) immediate recall, HVLT delayed recall and category-cued verbal fluency. The current series demonstrates promising neurocognitive effects of methylphenidate for long-COVID cognitive impairment, particularly in recall and verbal fluency domains.

BACKGROUND: Persistent post-COVID olfactory dysfunction continues to be studied due to the controversy in its pathophysiology and neuroimaging.
METHODS: The patients had confirmed mild COVID-19 infection with olfactory dysfunction of more than one month of evolution and they were compared to controls with normal olfaction, assessed using the Sniffin\' Sticks Olfactory Test and underwent brain, magnetic resonance imaging (MRI) of the olfactory bulb and olfactory function.
RESULTS: A total of 8 patients and 2 controls participated. The average age of the patients was 34.5 years (SD 8.5), and that of the controls was 28.5 (SD 2.1). The average score in the patients\' olfactory test was 7.9 points (SD 2.2). In brain and olfactory bulb MRI tests, no morphological differences were found. When evaluated by functional MRI, none of the patients activated the entorhinal area in comparison to the controls, who did show activation at this level. Activation of secondary olfactory areas in cases and controls were as follows: orbitofrontal (25% vs 100%), basal ganglia (25% vs 50%) and insula (38% vs 0%) respectively.
CONCLUSIONS: There were no observed morphological changes in the brain MRI. Unlike the controls, none of the patients activated the entorhinal cortex in the olfactory functional MRI.

Brain fog is a condition that is characterized by poor concentration, memory loss, decreased cognitive function, and mental fatigue. Although it is generally known as a long-term COVID-19 symptom, brain fog has also been reported to be caused by many other diseases. Thus, it is necessary to assess this condition in certain populations. This study aimed to evaluate the reliability and validity of the Brain Fog Scale in a Turkish population. We conducted the study in two phases. In a pilot study including 125 participants, we confirmed the suitability of the scale for validity analyses and then conducted exploratory (n = 230) and confirmatory factor analyses (n = 343). The Cronbach\'s alpha value of the 23-item Brain Fog Scale was 0.966. In addition, the 23-item and three-factor structure was confirmed as a result of the analyses. These three factors are mental fatigue, impaired cognitive acuity, and confusion. We also found that participants previously diagnosed with COVID-19 had higher brain fog scores. This finding indicates that brain fog is an important condition that can accompany COVID-19. Furthermore, this validated construct has an acceptable fit and is a valid and useful tool for the Turkish population.

OBJECTIVE: Brain fog and fatigue are common issues after acute coronary syndrome. However, little is known about the nature and impact of these experiences in spontaneous coronary artery dissection (SCAD) survivors. The aims of this study were to understand the experiences of brain fog and the coping strategies used after SCAD.
RESULTS: Participants were recruited from the Victor Chang Cardiac Research Institute Genetics Study database and were considered eligible if their event occurred within 12-months. Seven semi-structured online focus groups were conducted between December to January 2021-2022, with this study reporting findings related to brain fog and fatigue. Interviews were transcribed and thematically analysed using an iterative approach. Participants (N=30) were a mean age of 52.2 ((9.5) and mostly female (n=27, 90%). The overarching theme of brain fog after SCAD included four main themes: how brain fog is experienced, perceived causes, impacts, and how people cope. Experiences included memory lapses, difficulty concentrating and impaired judgement, and perceived causes included medication, fatigue and tiredness, and menopause and hormonal changes. Impacts of brain fog included rumination, changes in self-perception, disruption to hobbies/pastimes, and limitations at work. Coping mechanisms included setting reminders and expectations, being one\'s own advocate, lifestyle and self-determined medication adjustments, and support from peers.
CONCLUSIONS: Brain fog is experienced by SCAD survivors and the impacts are varied and numerous, including capacity to work. SCAD survivors reported difficulty understanding causes and found their own path to coping. Recommendations for clinicians are provided.

UNASSIGNED: Brain fog is associated with significant morbidity and reduced productivity and gained increasing attention after COVID-19. However, this subjective state has not been systematically characterised.
UNASSIGNED: To characterise self-reported brain fog.
UNASSIGNED: We systematically studied the cross-sectional associations between 29 a priori variables with the presence of \"brain fog.\" The variables were grouped into four categories: demographics, symptoms and functional impairments, comorbidities and potential risk factors (including lifestyle factors), and cognitive score. Univariate methods determined the correlates of brain fog, with long-COVID and non-long-COVID subgroups. XGBoost machine learning model retrospectively characterised subjective brain fog. Bonferroni-corrected statistical significance was set at 5%.
UNASSIGNED: Digital application for remote data collection.
UNASSIGNED: 25,796 individuals over the age of 18 who downloaded and completed the application.
UNASSIGNED: 7,280 of 25,796 individuals (28.2%) reported experiencing brain fog, who were generally older (mean brain fog 35.7 ± 11.9 years vs. 32.8 ± 11.6 years, p < 0.0001) and more likely to be female (OR = 1.2, p < 0.001). Associated symptoms and functional impairments included difficulty focusing or concentrating (OR = 3.3), feeling irritable (OR = 1.6), difficulty relaxing (OR = 1.2, all p < 0.0001), difficulty following conversations (OR = 2.2), remembering appointments (OR = 1.9), completing paperwork and performing mental arithmetic (ORs = 1.8, all p < 0.0001). Comorbidities included long-COVID-19 (OR = 3.8, p < 0.0001), concussions (OR = 2.4, p < 0.0001), and higher migraine disability assessment scores (MIDAS) (+34.1%, all p < 0.0001). Cognitive scores were marginally lower with brain fog (-0.1 std., p < 0.001). XGBoost achieved a training accuracy of 85% with cross-validated accuracy of 74%, and the features most predictive of brain fog in the model were difficulty focusing and following conversations, long-COVID, and severity of migraines.
UNASSIGNED: This is the largest study characterising subjective brain fog as an impairment of concentration associated with functional impairments in activities of daily living. Brain fog was particularly associated with a history of long-COVID-19, migraines, concussion, and with 0.1 standard deviations lower cognitive scores, especially on modified Stroop testing, suggesting impairments in the ability to inhibit cognitive interference. Further prospective studies in unselected brain fog sufferers should explore the full spectrum of brain fog symptoms to differentiate it from its associated conditions.

UNASSIGNED: One-third of individuals who contract novel coronavirus disease 2019 (COVID-19) reportedly experience persistent symptoms, including respiratory issues, headache, dizziness, taste disorders, fatigue, and various psychiatric and neurological symptoms, known as post-acute sequelae of SARS-CoV-2. In this case report, we present a patient who became aware of brain fog, which is cognitive impairment, approximately 2 months after their COVID-19 symptoms had resolved, accompanied by anxiety and depression.
UNASSIGNED: The patient, a 35-year-old Japanese man, was infected with COVID-19 and resumed work approximately 2 weeks later after symptoms improved. Approximately 1 month after returning to work, the patient\'s concentration became impaired and he started making noticeable errors at work. These symptoms did not improve, leading him to the outpatient clinic specializing in COVID-19 sequelae at our hospital. Here, he underwent blood tests, electroencephalography, and head magnetic resonance imaging, which did not reveal any abnormalities. Cognitive decline due to COVID-19 sequelae was therefore suspected, prompting his evaluation in our department approximately 5 months after his initial COVID-19 infection. Detailed cognitive function tests were performed. He was monitored without the use of medications, and his cognitive function gradually improved. Approximately 11 months after his initial COVID-19 infection, the same cognitive function tests were conducted again, because his subjective cognitive function symptoms had disappeared, and improvement was observed in many items.
UNASSIGNED: Since brain fog is a relatively common sequela, we emphasize the importance of keeping this in mind from the initial consultations and comparing results over time.

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Long Covid is a complex con­dition characterised by symptoms that per­sist for weeks and months after the Co­vid infection, accompanied by cognitive im­pairment that negatively affects daily life. Understanding this complex condition is im­portant for the development of diagnostic and therapeutic strategies.

This article aims to provide a comprehensive overview of cognitive impairment in long-COVID, including its definition, symptoms, pathophysiology, risk factors, assessment tools, imaging abnormalities, potential biomarkers, management strategies, long-term outcomes, and future directions for research.

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The search methodology used in this review aimed to include a wide range of research on cognitive impairment related to both COVID-19 and long-COVID. Systematic searches of PubMed and Google Scholar databases were conducted using a mixture of MeSH terms and keywords including ‘cognition’, ‘cognitive impairment’, ‘brain fog’, ‘COVID-19’ and ‘long-COVID’. The search was restricted to studies published in English between 1 January 2019 and 11 February 2024, which presented findings on neurological manifestations in human participants.

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Long-COVID is characterized by persistent symptoms following COVID-19 infection, with cognitive impairment being a prominent feature. Symptoms include brain fog, difficulties with concentration, memory issues, and executive function deficits. Pa­tho­physiological mechanisms involve vi­ral persistence, immune responses, and vas­cular damage. Risk factors include age, pre-existing conditions, and disease seve­rity. Cognitive assessment tools such as the Montreal Cognitive Assessment (MoCA) are essential for diagnosis. Imaging studies, including MRI, PET, and SPECT, reveal structural and functional brain alterations. Potential biomarkers include C-reactive protein, interleukin-6, and neuron-specific enolase. Management strategies encompass cognitive rehabilitation, occupational therapy, medications, and lifestyle modifications.

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Long-COVID poses a multifaceted challenge, and cognitive impairment significantly impacts patients’ lives. A multi­disciplinary approach, including cognitive rehabilitation and medication when appropriate, is essential for effective management. Future research should focus on validating biomarkers and understanding long-term cognitive outcomes.

Conclusion – Long-COVID is a global health concern, and cognitive impairment is a distressing symptom. While pharmacological interventions have potential, they require careful consideration. Continued research is crucial for improving the understanding and treatment of cognitive impairment in long-COVID.

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A hosszú Covid összetett állapot, amit a Covid-fertőzést követően hetekig és hónapokig fennmaradó tünetek jellemeznek, és a mindennapi életet negatívan befolyásoló kognitív károsodás kísér. Ennek az összetett állapotnak a megértése fontos a diagnosztikus és terápiás stratégiák kifejlesztéséhez.
E cikk célja, hogy átfogó áttekintést nyújtson a hosszú Covidban jelentkező kog­nitív károsodásról, beleértve a definíciót, a tü­neteket, a patofiziológiát, a kockázati té­nyezőket, az értékelési eszközöket, a kép­alkotó eljárásokkal felfedezhető eltéréseket, a lehetséges biomarkereket, a kezelési stra­té­giákat, a hosszú távú kimeneteket és a ku­ta­tás jövőbeli irányait.

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Az áttekintés keresési módszertanának célja az volt, hogy a Covid-19-hez és a hosszú Covidhoz kapcsolódó kognitív károsodással kapcsolatos kutatások széles körét tartalmazza. A PubMed és a Google Scholar adatbázisokban végeztünk sziszte­ma­tikus keresést a MeSH terminusok és kulcs­szavak – beleértve a „kogníció”, „kognitív károsodás”, „agyi köd/brain fog”, „COVID-19” és „long-COVID” kifejezéseket – kombináció­jának felhasználásával. A keresést azokra a 2019. január 1. és 2024. február 11. között angol nyelven megjelent tanulmányokra kor­látoztuk, amelyek humán neurológiai meg­nyilvánulásokra vonatkozó eredményeket mutattak be.

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A hosszú Covidot a Covid-19-fertőzést követően fennmaradó tartós tünetek jellemzik, amelyek közül kiemelkedik a kognitív károsodás. A tünetek közé tartozik az agyi köd, a koncentrációs nehézségek, a memóriaproblémák és a végrehajtó funkciók hiányosságai. A patofiziológiai mechanizmusok a vírusperzisztenciát, az immunválaszt és az érrendszeri károsodást foglalják magukba. A kockázati tényezők közé tartozik az életkor, a már meglévő betegségek és a Covid-19-fertőzés súlyossága. A diagnózis felállításához elengedhetetlenek a kognitív értékelő eszközök, mint például a Montreal Cognitive Assessment (MoCA). A képalkotó vizsgálatok, beleértve az MRI-t, a PET-et és a SPECT-et, strukturális és funkcionális agyi elváltozásokat tárnak fel. A potenciális biomarkerek közé tartozik a C-reaktív fehérje, az interleukin-6 és a neuronspecifikus enoláz. A kezelési stratégiák közé tartozik a kognitív rehabilitáció, a foglalkozásterápia, a gyógyszeres kezelés és az életmódváltás.

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Megbeszélés – A hosszú Covid sokrétű kihívást jelent, és a vele járó kognitív károsodás jelentősen befolyásolja a betegek életét. A hatékony kezeléshez elengedhetetlen a multidiszciplináris megközelítés, beleértve a kognitív rehabilitációt és adott esetben a gyógyszeres kezelést. A jövőbeli kutatásoknak a biomarkerek validálására és a hosszú távú kognitív kimenet megértésére kell összpontosítaniuk.

A hosszú Covid, aminek a kognitív károsodás aggasztó tünete, globális egészségügyi problémát jelent. Bár a farmakológiai beavatkozásokban rejlik potenciál, használatuk alapos megfontolást igényel. 
A további kutatás elengedhetetlen a hosszú Covid esetében jelentkező kognitív károsodás megértése és kezelésének javítása érdekében.

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