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Abstract
Background
Cognitive impairment, colloquially termed “brain fog”, is one of the most prevalent manifestations of post-Covid syndrome and a major contributor to impaired daily function and reduced quality of life. However, despite the high numbers of affected individuals presenting to clinical services with cognitive impairment, little work has been undertaken to date on the suitability of current memory clinic tests for identifying the cognitive deficits in this new acquired cognitive disorder.
The aim of this study was therefore to determine the performance of people with post-Covid syndrome presenting with cognitive impairment on the Addenbrooke's Cognitive Examination-III (ACE-III), a cognitive test used widely in memory clinics. A subset of individuals also underwent testing on a novel battery of short digital tests assessing attention, speed of information processing and executive function, representing the domains primarily implicated in post-Covid cognitive dysfunction.
Methods
102 individuals with post-Covid syndrome presenting with subjective cognitive complaints were recruited from a specialist cognitive long Covid clinic at University Hospitals Sussex NHS Trust. All participants completed self-report questionnaires on depression, anxiety, sleep and fatigue. Cognitive performance was assessed using the ACE-III, with 20 participants also being tested on the digital Long COVID Assessment Battery (LCCAB) (N = 20).
Results
The overall sample had a mean ACE-III score of 91/100 (SD 6) with 15.7% (16/102) scoring at or below the cut-off score considered to represent objective cognitive impairment. Of the 20 individuals who also completed the LCCAB, 89.47% were impaired on at least one task, primarily in the domains of attention, executive function and processing speed. Cognitive performance was not associated with depression, anxiety, sleep quality or fatigue.
Conclusion
The vast majority of individuals with post-Covid syndrome presenting with subjective cognitive complaints do not exhibit impaired performance on the ACE-III. This likely reflects the historical use of ACE-III and other pen and paper cognitive tests to detect cognitive impairment in diseases causing dementia, but they are ill-equipped to identify impairment in those cognitive domains affected in post-Covid syndrome. The LCCAB detected cognitive impairments in nearly 90% of participants, primarily affecting attention, executive function, and processing speed. These observations highlight the need for alternative cognitive tests for use in routine clinical practice to detect the impairments in new acquired cognitive disorders that are not adequately captured by legacy tests.
Patients recovering from COVID-19 commonly exhibit cognitive and brain alterations, yet the specific neuropathological mechanisms and risk factors underlying these alterations remain elusive. Given the significant global incidence of COVID-19, identifying factors that can distinguish individuals at risk of developing brain alterations is crucial for prioritizing follow-up care. Here, we report findings from a sample of patients consisting of 73 adults with a mild to moderate SARS-CoV-2 infection without signs of respiratory failure and 27 with infections attributed to other agents and no history of COVID-19. The participants underwent cognitive screening, a decision-making task, and MRI evaluations. We assessed for the presence of anosmia and the requirement for hospitalization. Groups did not differ in age or cognitive performance. Patients who presented with anosmia exhibited more impulsive alternative changes after a shift in probabilities (r = − 0.26, p = 0.001), while patients who required hospitalization showed more perseverative choices (r = 0.25, p = 0.003). Anosmia correlated with brain measures, including decreased functional activity during the decision-making task, thinning of cortical thickness in parietal regions, and loss of white matter integrity. Hence, anosmia could be a factor to be considered when identifying at-risk populations for follow-up.
Background
COVID-19 survivors may experience a wide range of chronic cognitive symptoms for months or years as part of post-COVID-19 conditions (PCC). To date, there is no definitive objective cognitive marker for PCC. We hypothesised that a key common deficit in people with PCC might be generalised cognitive slowing.
Methods
To examine cognitive slowing, patients with PCC completed two short web-based cognitive tasks, Simple Reaction Time (SRT) and Number Vigilance Test (NVT). 270 patients diagnosed with PCC at two different clinics in UK and Germany were compared to two control groups: individuals who contracted COVID-19 before but did not experience PCC after recovery (No-PCC group) and uninfected individuals (No-COVID group). All patients with PCC completed the study between May 18, 2021 and July 4, 2023 in Jena University Hospital, Jena, Germany and Long COVID clinic, Oxford, UK.
Findings
We identified pronounced cognitive slowing in patients with PCC, which distinguished them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. Cognitive slowing was evident even on a 30-s task measuring simple reaction time (SRT), with patients with PCC responding to stimuli ∼3 standard deviations slower than healthy controls. 53.5% of patients with PCC's response speed was slower than 2 standard deviations from the control mean, indicating a high prevalence of cognitive slowing in PCC. This finding was replicated across two clinic samples in Germany and the UK. Comorbidities such as fatigue, depression, anxiety, sleep disturbance, and post-traumatic stress disorder did not account for the extent of cognitive slowing in patients with PCC. Furthermore, cognitive slowing on the SRT was highly correlated with the poor performance of patients with PCC on the NVT measure of sustained attention.
Interpretation
Together, these results robustly demonstrate pronounced cognitive slowing in people with PCC, which distinguishes them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. This might be an important factor contributing to some of the cognitive impairments reported in patients with PCC.
Funding
10.13039/100010269Wellcome Trust (206330/Z/17/Z), NIHR Oxford Health Biomedical Research Centre, the Thüringer Aufbaubank (2021 FGI 0060), German Forschungsgemeinschaft (DFG, FI 1424/2-1) and the 10.13039/100010661Horizon 2020 Framework Programme of the 10.13039/501100000780European Union (ITN SmartAge, H2020-MSCA-ITN-2019-859890).
Background
A fraction of patients with asymptomatic to mild/moderate acute COVID-19 disease report cognitive deficits as part of the post-COVID-19 syndrome. This study aimed to assess the neuropsychological profile of these patients.
Methods
Assessment at baseline (three months or more following acute COVID-19) of a monocentric prospective cohort of patients with post-COVID-19 syndrome. Multidomain neuropsychological tests were performed, and questionnaires on depression, anxiety, fatigue, sleep, and general health status were administered.
Results
Of the 58 patients screened, six were excluded due to possible alternative causes of cognitive impairment (major depression, neurodegenerative disease). Of the remaining 52 individuals, only one had a below-threshold screening result on Mini-Mental State Examination, and 13 scored below the cut-off on Montreal Cognitive Assessment. Extended neuropsychological testing revealed a neurocognitive disorder (NCD) in 31 (59.6%) participants with minor NCD in the majority of cases ( n = 26). In patients with NCD, the cognitive domains learning/memory and executive functions were impaired in 60.7%, complex attention in 51.6%, language in 35.5%, and perceptual-motor function in 29.0%. Cognitive profiles were associated with daytime sleepiness but not with depression, anxiety, sleep quality, total general health status, or fatigue.
Conclusion
Neurocognitive impairment can be confirmed in around 60% of individuals with self-reported deficits as part of post-COVID-19 syndrome following a mild acute COVID-19 disease course. Notably, screening tests cannot reliably detect this dysfunction. Standard psychiatric assessments showed no association with cognitive profiles. Longitudinal studies are needed to further evaluate the course of neurocognitive deficits and clarify pathophysiology.
The COVID-19 outbreak has infected people all over the world where many clinics are being constructed to diagnose and treat lingering symptoms or long COVID. Neurological and long-term cognitive consequences are very worrisome. Many of COVID-19’s neurological symptoms are likely the result of the body’s extensive immunological response to infection rather than the virus attacking the brain or nervous system directly. At the same time, the extent and type of COVID-19’s cognitive consequences are unknown. The goal of this study was to assess the cognitive functions of healthcare workers 2 weeks to 3 months after COVID-19 infection. Ninety-two healthcare workers participated in the study; 32 were post-COVID-19 cases, and 60 were healthy people (the comparison group). The cognitive functions of the participants were assessed using the Addenbrooke’s Cognitive Examination (ACE-III) test, which evaluated attention, memory, language, and visuospatial skills, as well as the Arabic version of the Patient Health Questionnaire Anxiety GAD-7 and Depression Assessments PHQ-9. The study revealed that there was a highly significant direct correlation between post-infection with COVID-19 and scores of both anxiety and depression and an inverse correlation in the case of attention and memory. On the other hand, there is no statistical effect of post-COVID-19 on verbal fluency, language scores, and visio-spatial abilities. Using multiple linear regression, there was a powerful significant decrease effect of post-COVID-19 on memory scores controlling both anxiety and depression degrees (Beta = − 0.745, P < 0.001). Also, there was a strong negative correlation post-COVID-19 on attention scores controlling both anxiety and depression degrees (Beta = − 0.745, P < 0.001). The study showed a strong negative effect of post-COVID-19 on the attention and memory of patients. Furthermore, both anxiety and depression scores increased significantly among the post-COVID-19 patients.
People with a depressed mood tend to perform poorly on executive function tasks, which require much of the prefrontal cortex (PFC), an area of the brain which has also been shown to be hypo-active in this population. Recent research has suggested that these aspects of cognition might be improved through physical activity and cognitive training. However, whether the acute effects of exercise on PFC activation during executive function tasks vary with depressive symptoms remains unclear. To investigate these effects, 106 participants were given a cardiopulmonary exercise test (CPET) and were administered a set of executive function tests directly before and after the CPET assessment. The composite effects of exercise on the PFC (all experimental blocks) showed bilateral activation changes in dorsolateral (BA46/9) and ventrolateral (BA44/45) PFC, with the greatest changes occurring in rostral PFC (BA10). The effects observed in right ventrolateral PFC varied depending on level of depressive symptoms (13% variance explained); the changes in activation were less for higher levels. There was also a positive relationship between CPET scores (VO2peak) and right rostral PFC, in that greater activation changes in right BA10 were predictive of higher levels of aerobic fitness (9% variance explained). Since acute exercise ipsilaterally affected this PFC subregion and the inferior frontal gyrus during executive function tasks, this suggests physical activity might benefit the executive functions these subregions support. And because physical fitness and depressive symptoms explained some degree of cerebral upregulation to these subregions, physical activity might more specifically facilitate the engagement of executive functions that are typically associated with hypoactivation in depressed populations. Future research might investigate this possibility in clinical populations, particularly the neural effects of physical activity used in combination with mental health interventions.
Background:
There has been a significant increase in number of patients seeking neuropsychological rehabilitation months after the acute phase of COVID-19 infection.
Objective:
Identify the cognitive and psychiatric disorders in patients with long COVID or Post-Acute Sequelae of COVID (PASC) and explore the association between disease severity during the acute phase and persistent neuropsychological manifestations.
Methods:
614 adults were assessed an average of eight months post-infection. Participants were, on average, 47.6 y.o., who sought rehabilitation for neuropsychological problems. Patients were evaluated using the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS), Phonemic Verbal Fluency and Clock Drawing tests (NEUPSILIN) for executive functions, and the Hospital Anxiety and Depression Scale (HADS).
Results:
The BNIS score was significantly below reference values in all subscales, especially affect and memory. Verbal Fluency and Clock Drawing subtest results were also lower. Patients with PASC tested high for anxiety/depression, but there was no statistically significant relationship between HADS and BNIS scores. Neuropsychological evaluations showed no differences in cognitive or psychiatric profiles between hospitalized and non-hospitalized patients.
Conclusions:
Neuropsychological results suggest executive function problems and high incidence of anxiety/depression, irrespective of acute-phase severity, underscoring a need for neurorehabilitation programs while providing data for public policy initiatives.
Introduction:
We conducted a systematic review and meta-analysis of the cognitive effects of coronavirus disease 2019 (COVID-19) in adults with no prior history of cognitive impairment.
Methods:
Searches in Medline/Web of Science/Embase from January 1, 2020, to December 13, 2021, were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A meta-analysis of the Montreal Cognitive Assessment (MoCA) total score comparing recovered COVID-19 and healthy controls was performed.
Results:
Oof 6202 articles, 27 studies with 2049 individuals were included (mean age = 56.05 years, evaluation time ranged from the acute phase to 7 months post-infection). Impairment in executive functions, attention, and memory were found in post-COVID-19 patients. The meta-analysis was performed with a subgroup of 290 individuals and showed a difference in MoCA score between post-COVID-19 patients versus controls (mean difference = -0.94, 95% confidence interval [CI] -1.59, -0.29; P = .0049).
Discussion:
Patients recovered from COVID-19 have lower general cognition compared to healthy controls up to 7 months post-infection.
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been often characterized as a respiratory disease. However, it is increasingly being understood as an infection that impacts multiple systems, and many patients report neurological symptoms. Indeed, there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere. There are several mechanisms by which the COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and cognitive problems are one of the most commonly reported symptoms in those experiencing Long COVID – the chronic illness following the COVID-19 infection that affects between 10 and 25% of patients. However, there is yet little research testing cognition in Long COVID. The COVID and Cognition Study is a cross-sectional/longitudinal study aiming to understand cognitive problems in Long COVID. The first paper from the study explored the characteristics of our sample of 181 individuals who had experienced the COVID-19 infection, and 185 who had not, and the factors that predicted ongoing symptoms and self-reported cognitive deficits. In this second paper from the study, we assess this sample on tests of memory, language, and executive function. We hypothesize that performance on “objective” cognitive tests will reflect self-reported cognitive symptoms. We further hypothesize that some symptom profiles may be more predictive of cognitive performance than others, perhaps giving some information about the mechanism. We found a consistent pattern of memory deficits in those that had experienced the COVID-19 infection, with deficits increasing with the severity of self-reported ongoing symptoms. Fatigue/Mixed symptoms during the initial illness and ongoing neurological symptoms were predictive of cognitive performance.
Background:
Cognitive dysfunction has been observed following recovery from COVID-19. To the best of our knowledge, however, no study has assessed the progression of cognitive impairment after one year. We aimed to assess cognitive functioning at one year from hospital discharge, and eventual associations with specific clinical variables.
Methods:
We recruited 76 patients (aged 22-74) who had been hospitalized for COVID-19. Patients received neuropsychological assessments at 5 (n= 76) and 12 months (n= 53) from hospital discharge.
Results:
Over half (63.2%) of the patients had deficits in at least one test at five months. Compared to the assessment at 5 months, verbal memory, attention and processing speed improved significantly after one year (all P<0.05), whereas visuospatial memory did not (all P>0.500). The most affected domains after one year were processing speed (28.3%), long-term visuospatial (18.1%) and verbal (15.1%) memory. Lower PaO2/FiO2 ratios in the acute phase were associated with worse verbal long-term memory (P=0.029) and visuospatial learning (P=0.041) at five months. Worse visuospatial long-term memory at five months was associated with hyposmia (P=0.020) and dysgeusia (P=0.037).
Conclusion:
Our study expands the results from previous studies, showing that cognitive impairment can still be observed after one year. Patients with severe COVID-19 should receive periodic cognitive follow-up evaluations, as cognitive deficits in recovered patients could have social and occupational implications.
Background
Long Covid is a public health concern that needs defining, quantifying, and describing. We aimed to explore the initial and ongoing symptoms of Long Covid following SARS-CoV-2 infection and describe its impact on daily life.
Methods
We collected self-reported data through an online survey using convenience non-probability sampling. The survey enrolled adults who reported lab-confirmed (PCR or antibody) or suspected COVID-19 who were not hospitalised in the first two weeks of illness. This analysis was restricted to those with self-reported Long Covid. Univariate comparisons between those with and without confirmed COVID-19 infection were carried out and agglomerative hierarchical clustering was used to identify specific symptom clusters, and their demographic and functional correlates.
Results
We analysed data from 2550 participants with a median duration of illness of 7.6 months (interquartile range (IQR) 7.1–7.9). 26.5% reported lab-confirmation of infection. The mean age was 46.5 years (standard deviation 11 years) with 82.8% females and 79.9% of participants based in the UK. 89.5% described their health as good, very good or excellent before COVID-19. The most common initial symptoms that persisted were exhaustion, chest pressure/tightness, shortness of breath and headache. Cognitive dysfunction and palpitations became more prevalent later in the illness. Most participants described fluctuating (57.7%) or relapsing symptoms (17.6%). Physical activity, stress, and sleep disturbance commonly triggered symptoms. A third (32%) reported they were unable to live alone without any assistance at six weeks from start of illness. 16.9% reported being unable to work solely due to COVID-19 illness. 37.0% reported loss of income due to illness, and 64.4% said they were unable to perform usual activities/duties. Acute systems clustered broadly into two groups: a majority cluster (n = 2235, 88%) with cardiopulmonary predominant symptoms, and a minority cluster (n = 305, 12%) with multisystem symptoms. Similarly, ongoing symptoms broadly clustered in two groups; a majority cluster (n = 2243, 88.8%) exhibiting mainly cardiopulmonary, cognitive symptoms and exhaustion, and a minority cluster (n = 283, 11.2%) exhibiting more multisystem symptoms. Belonging to the more severe multisystem cluster was associated with more severe functional impact, lower income, younger age, being female, worse baseline health, and inadequate rest in the first two weeks of the illness, with no major differences in the cluster patterns when restricting analysis to the lab-confirmed subgroup.
Conclusion
This is an exploratory survey of Long Covid characteristics. Whilst this is a non-representative population sample, it highlights the heterogeneity of persistent symptoms, and the significant functional impact of prolonged illness following confirmed or suspected SARS-CoV-2 infection. To study prevalence, predictors and prognosis, research is needed in a representative population sample using standardised case definitions.
Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases.
Importance
Previous studies of post-acute COVID-19 syndrome have focused on critical cases with severe disease. However, most cases are mild to moderate in disease severity.
Objective
We aimed to examine cognitive outcomes in cases of non-critical, mild-to-moderate COVID-19. Design, Setting, and Participants: In this cross-sectional study, we enrolled 72 adults aged 22 to 65 years in Central Texas who had non-critical, mild-to-moderate COVID-19 infection between 13 January 2021 and 20 April 2021.
Main Outcomes and Measures
We remotely administered cognitive-behavioral testing to determine the frequency of cognitive impairment and examine demographic, clinical, and psychosocial contributors to impairment.
Results
The frequency of objective cognitive impairment was 40%. The largest number of participants (24%) showed impairment on a measure of executive functioning. Attention and processing speed was more impaired in males (OR = 1.5, 95%CI = 0.23–2.9). Males endorsed lower adherence to social distancing guidelines (U = 590, p = 0.01), which was in turn associated with cognitive impairment across participants (r = −0.30, p = 0.01). Younger age was correlated with impairment (r = −0.26, p = 0.03) but was also associated with racial/ethnic minority status (r = −0.31, p = 0.01) and increased psychological symptoms (p < 0.04). Greater number of COVID-19 symptoms was correlated with lower subjective cognitive function (r = −0.38, p = 0.001) as well as psychosocial function (r > 0.24, p < 0.05). Moderate COVID-19 severity was associated with attention/processing speed impairment (r = 0.27, p = 0.03), increased pain (r = 0.31, p = 0.01), and higher number of COVID-19 symptoms (r = 0.32, p = 0.01).
Conclusion and Relevance
Mild or moderate COVID-19 infection may be associated with cognitive impairments, especially in the domain of executive functioning. A subgroup of younger individuals may be more vulnerable to cognitive and psychosocial effects of COVID-19.
Highlights
Question: How frequent is cognitive impairment among non-critical, mild-to-moderate COVID-19 survivors?
Findings
In this cross-sectional study of 72 adults, 40% demonstrated cognitive impairment, particularly in executive function.
Meaning
Neurologic sequelae, such as cognitive impairment, may be common following COVID-19 infection.
Objective
To explore the lived experience of ‘brain fog’—the wide variety of neurocognitive symptoms that can follow COVID-19.
Design and setting
A UK-wide longitudinal qualitative study comprising online focus groups with email follow-up.
Method
50 participants were recruited from a previous qualitative study of the lived experience of long COVID-19 (n=23) and online support groups for people with persistent neurocognitive symptoms following COVID-19 (n=27). In remotely held focus groups, participants were invited to describe their neurocognitive symptoms and comment on others’ accounts. Individuals were followed up by email 4–6 months later. Data were audiotaped, transcribed, anonymised and coded in NVIVO. They were analysed by an interdisciplinary team with expertise in general practice, clinical neuroscience, the sociology of chronic illness and service delivery, and checked by people with lived experience of brain fog.
Results
Of the 50 participants, 42 were female and 32 white British. Most had never been hospitalised for COVID-19. Qualitative analysis revealed the following themes: mixed views on the appropriateness of the term ‘brain fog’; rich descriptions of the experience of neurocognitive symptoms (especially executive function, attention, memory and language), accounts of how the illness fluctuated—and progressed over time; the profound psychosocial impact of the condition on relationships, personal and professional identity; self-perceptions of guilt, shame and stigma; strategies used for self-management; challenges accessing and navigating the healthcare system; and participants’ search for physical mechanisms to explain their symptoms.
Conclusion
These qualitative findings complement research into the epidemiology and mechanisms of neurocognitive symptoms after COVID-19. Services for such patients should include: an ongoing therapeutic relationship with a clinician who engages with their experience of neurocognitive symptoms in its personal, social and occupational context as well as specialist services that include provision for neurocognitive symptoms, are accessible, easily navigable, comprehensive and interdisciplinary.
Recent studies indicate that COVID-19 infection can lead to serious neurological consequences in a small percentage of individuals. However, in the months following acute illness, many more suffer from fatigue, low motivation, disturbed mood, poor sleep and cognitive symptoms, colloquially referred to as 'brain fog'. But what about individuals who had asymptomatic to moderate COVID-19 and reported no concerns after recovering from COVID-19? Here, we examined a wide range of cognitive functions critical for daily life (including sustained attention, memory, motor control, planning, semantic reasoning, mental rotation and spatial-visual attention) in people who had previously suffered from COVID-19 but were not significantly different from a control group on self-reported fatigue, forgetfulness, sleep abnormality, motivation, depression, anxiety and personality profile. Reassuringly, COVID-19 survivors performed well in most abilities tested, including working memory, executive function, planning and mental rotation. However, they displayed significantly worse episodic memory (up to 6 months post-infection) and greater decline in vigilance with time on task (for up to 9 months). Overall, the results show that specific chronic cognitive changes following COVID-19 are evident on objective testing even amongst those who do not report a greater symptom burden. Importantly, in the sample tested here, these were not significantly different from normal after 6-9 months, demonstrating evidence of recovery over time.
Aims
Long-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with controls from the general population.
Methods and results
Four hundred and forty-three mainly non-hospitalized individuals were examined in median 9.6 months after the first positive SARS-CoV-2 test and matched for age, sex, and education with 1328 controls from a population-based German cohort. We assessed pulmonary, cardiac, vascular, renal, and neurological status, as well as patient-related outcomes. Bodyplethysmography documented mildly lower total lung volume (regression coefficient −3.24, adjusted P = 0.014) and higher specific airway resistance (regression coefficient 8.11, adjusted P = 0.001) after SARS-CoV-2 infection. Cardiac assessment revealed slightly lower measures of left (regression coefficient for left ventricular ejection fraction on transthoracic echocardiography −0.93, adjusted P = 0.015) and right ventricular function and higher concentrations of cardiac biomarkers (factor 1.14 for high-sensitivity troponin, 1.41 for N-terminal pro-B-type natriuretic peptide, adjusted P ≤ 0.01) in post-SARS-CoV-2 patients compared with matched controls, but no significant differences in cardiac magnetic resonance imaging findings. Sonographically non-compressible femoral veins, suggesting deep vein thrombosis, were substantially more frequent after SARS-CoV-2 infection (odds ratio 2.68, adjusted P < 0.001). Glomerular filtration rate (regression coefficient −2.35, adjusted P = 0.019) was lower in post-SARS-CoV-2 cases. Relative brain volume, prevalence of cerebral microbleeds, and infarct residuals were similar, while the mean cortical thickness was higher in post-SARS-CoV-2 cases. Cognitive function was not impaired. Similarly, patient-related outcomes did not differ.
Conclusion
Subjects who apparently recovered from mild to moderate SARS-CoV-2 infection show signs of subclinical multi-organ affection related to pulmonary, cardiac, thrombotic, and renal function without signs of structural brain damage, neurocognitive, or quality-of-life impairment. Respective screening may guide further patient management.
Diagnosing dementia can be challenging for clinicians, given the array of factors that contribute to changes in cognitive function. The Addenbrooke’s Cognitive Examination III (ACE-III) is commonly used in dementia assessments, covering the domains of attention, memory, fluency, visuospatial and language. This study aims to (1) assess the reliability of ACE-III to differentiate between dementia, mild cognitive impairment (MCI) and controls and (2) establish whether the ACE-III is useful for diagnosing dementia subtypes. Client records from the Northern Health and Social Care Trust (NHSCT) Memory Service ( n = 2,331, 2013–2019) were used in the analysis including people diagnosed with Alzheimer’s disease ( n = 637), vascular dementia ( n = 252), mixed dementia ( n = 490), MCI ( n = 920) and controls ( n = 32). There were significant differences in total ACE-III and subdomain scores between people with dementia, MCI and controls ( p < 0.05 for all), with little overlap between distribution of total ACE-III scores (< 39%) between groups. The distribution of total ACE-III and subdomain scores across all dementias were similar. There were significant differences in scores for attention, memory and fluency between Alzheimer’s disease and mixed dementia, and for visuospatial and language between Alzheimer’s disease–vascular dementia ( p < 0.05 for all). However, despite the significant differences across these subdomains, there was a high degree of overlap between these scores (> 73%) and thus the differences are not clinically relevant. The results suggest that ACE-III is a useful tool for discriminating between dementia, MCI and controls, but it is not reliable for discriminating between dementia subtypes. Nonetheless, the ACE-III is still a reliable tool for clinicians that can assist in making a dementia diagnosis in combination with other factors at assessment.
Background
A significant number of patients with COVID-19 experience prolonged symptoms, known as Long COVID. Few systematic studies have investigated this population, particularly in outpatient settings. Hence, relatively little is known about symptom makeup and severity, expected clinical course, impact on daily functioning, and return to baseline health.
Methods
We conducted an online survey of people with suspected and confirmed COVID-19, distributed via COVID-19 support groups (e.g. Body Politic, Long COVID Support Group, Long Haul COVID Fighters) and social media (e.g. Twitter, Facebook). Data were collected from September 6, 2020 to November 25, 2020. We analyzed responses from 3762 participants with confirmed (diagnostic/antibody positive; 1020) or suspected (diagnostic/antibody negative or untested; 2742) COVID-19, from 56 countries, with illness lasting over 28 days and onset prior to June 2020. We estimated the prevalence of 203 symptoms in 10 organ systems and traced 66 symptoms over seven months. We measured the impact on life, work, and return to baseline health.
Findings
For the majority of respondents (>91%), the time to recovery exceeded 35 weeks. During their illness, participants experienced an average of 55.9+/- 25.5 (mean+/-STD) symptoms, across an average of 9.1 organ systems. The most frequent symptoms after month 6 were fatigue, post-exertional malaise, and cognitive dysfunction. Symptoms varied in their prevalence over time, and we identified three symptom clusters, each with a characteristic temporal profile. 85.9% of participants (95% CI, 84.8% to 87.0%) experienced relapses, primarily triggered by exercise, physical or mental activity, and stress. 86.7% (85.6% to 92.5%) of unrecovered respondents were experiencing fatigue at the time of survey, compared to 44.7% (38.5% to 50.5%) of recovered respondents. 1700 respondents (45.2%) required a reduced work schedule compared to pre-illness, and an additional 839 (22.3%) were not working at the time of survey due to illness. Cognitive dysfunction or memory issues were common across all age groups (~88%). Except for loss of smell and taste, the prevalence and trajectory of all symptoms were similar between groups with confirmed and suspected COVID-19.
Interpretation
Patients with Long COVID report prolonged, multisystem involvement and significant disability. By seven months, many patients have not yet recovered (mainly from systemic and neurological/cognitive symptoms), have not returned to previous levels of work, and continue to experience significant symptom burden.
Funding
All authors contributed to this work in a voluntary capacity. The cost of survey hosting (on Qualtrics) and publication fee was covered by AA's research grant (Wellcome Trust/Gatsby Charity via Sainsbury Wellcome center, UCL).
Central and peripheral nervous system involvement during acute COVID-19 is well known. Although many patients report some subjective symptoms months after the infection, the exact incidence of neurological and cognitive sequelae of COVID-19 remains to be determined. The aim of this study is to investigate if objective neurological or cognitive impairment is detectable four months after SARS-CoV-2 infection, in a group of patients who had mild–moderate COVID-19. A cohort of 120 health care workers previously affected by COVID-19 was examined 4 months after the diagnosis by means of neurological and extensive cognitive evaluation and compared to a group of 30 health care workers who did not have COVID-19 and were similar for age and co morbidities. At 4 month follow-up, 118/120 COVID-19 cases had normal neurological examination, two patients had neurological deficits. COVID-19 patients did not show general cognitive impairment at MMSE. In COVID-19 cases the number of impaired neuropsychological tests was not significantly different from non COVID-19 cases (mean 1.69 and 1 respectively, Mann–Whitney p = n.s.), as well as all the mean tests’ scores. Anxiety, stress and depression scores resulted to be significantly higher in COVID-19 than in non COVID-19 cases. The results do not support the presence of neurological deficits or cognitive impairment in this selected population of mild–moderate COVID-19 patients four months after the diagnosis. Severe emotional disorders in patients who had COVID-19 in the past are confirmed.
Objective
Most SARS‐CoV‐2‐infected individuals never require hospitalization. However, some develop prolonged symptoms. We sought to characterize the spectrum of neurologic manifestations in non‐hospitalized Covid‐19 “long haulers”.
Methods
This is a prospective study of the first 100 consecutive patients (50 SARS‐CoV‐2 laboratory‐positive and 50 laboratory‐negative individuals) presenting to our Neuro‐Covid‐19 clinic between May and November 2020. Due to early pandemic testing limitations, patients were included if they met Infectious Diseases Society of America symptoms of Covid‐19, were never hospitalized for pneumonia or hypoxemia and had neurologic symptoms lasting over 6 weeks. We recorded the frequency of neurologic symptoms and analyzed patient‐reported quality of life measures and standardized cognitive assessments.
Results
Mean age was 43.2±11.3 years, 70% were female and 48% were evaluated in televisits. The most frequent comorbidities were depression/anxiety (42%) and autoimmune disease (16%). The main neurologic manifestations were: “brain fog” (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), myalgias (55%), with only anosmia being more frequent in SARS‐CoV‐2⁺ than SARS‐CoV‐2‐ patients (37/50 [74%] vs (18/50 [36%]; p <0.001). Moreover, 85% also experienced fatigue. There was no correlation between time from disease onset and subjective impression of recovery. Both groups exhibited impaired quality of life in cognitive and fatigue domains. SARS‐CoV‐2⁺ patients performed worse in attention and working memory cognitive tasks compared to a demographic‐matched US population (T‐score 41.5 [37, 48.25] and 43 [37.5, 48.75], respectively; both p<0.01).
Interpretation
Non‐hospitalized Covid‐19 “long haulers” experience prominent and persistent “brain fog” and fatigue that affect their cognition and quality of life.
Considering the mechanisms capable of causing brain alterations in COVID-19, we aimed to study the occurrence of cognitive abnormalities in the months following hospital discharge. We recruited 38 (aged 22–74 years; 27 males) patients hospitalized for complications of SARS-CoV-2 infection in nonintensive COVID units. Participants underwent neuropsychological testing about 5 months after hospital discharge. Of all patients, 42.1% had processing speed deficits, while 26.3% showed delayed verbal recall deficits. Twenty-one percent presented with deficits in both processing speed and verbal memory. Bivariate analysis revealed a positive correlation between the lowest arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) (P/F) ratio during hospitalization and verbal memory consolidation performance (SRT-LTS score, r = 0.404, p = 0.027), as well as a positive correlation between SpO2 levels upon hospital arrival and delayed verbal recall performance (SRT-D score, rs = 0.373, p = 0.042). Acute respiratory distress syndrome (ARDS) during hospitalization was associated with worse verbal memory performance (ARDS vs. no ARDS: SRT-LTS mean score = 30.63 ± 13.33 vs. 44.50 ± 13.16, p = 0.007; SRT-D mean score = 5.95 ± 2.56 vs. 8.10 ± 2.62, p = 0.029). Cognitive abnormalities can frequently be found in COVID-19 patients 5 months after hospital discharge. Increased fatigability, deficits of concentration and memory, and overall decreased cognitive speed months after hospital discharge can interfere with work and daily activities.
Introduction
COVID-19 complications can include neurological, psychiatric, psychological, and psychosocial impairments. Little is known on the consequences of SARS-COV-2 on cognitive functions of patients in the sub-acute phase of the disease. We aimed to investigate the impact of COVID-19 on cognitive functions of patients admitted to the COVID-19 Rehabilitation Unit of the San Raffaele Hospital (Milan, Italy).
Material and methods
87 patients admitted to the COVID-19 Rehabilitation Unit from March 27th to June 20th 2020 were included. Patients underwent Mini Mental State Evaluation (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Rating Scale for Depression, and Functional Independence Measure (FIM). Data were divided in 4 groups according to the respiratory assistance in the acute phase: Group1 (orotracheal intubation), Group2 (non-invasive ventilation using Biphasic Positive Airway Pressure), Group3 (Venturi Masks), Group4 (no oxygen therapy). Follow-ups were performed at one month after home-discharge.
Results
Out of the 87 patients (62 Male, mean age 67.23 ± 12.89 years), 80% had neuropsychological deficits (MoCA and MMSE) and 40% showed mild-to-moderate depression. Group1 had higher scores than Group3 for visuospatial/executive functions (p = 0.016), naming (p = 0.024), short- and long-term memory (p = 0.010, p = 0.005), abstraction (p = 0.024), and orientation (p = 0.034). Group1 was younger than Groups2 and 3. Cognitive impairments correlated with patients’ age. Only 18 patients presented with anosmia. Their data did not differ from the other patients. FIM (<100) did not differ between groups. Patients partly recovered at one-month follow-up and 43% showed signs of post-traumatic stress disorder.
Conclusion
Patients with severe functional impairments had important cognitive and emotional deficits which might have been influenced by the choice of ventilatory therapy, but mostly appeared to be related to aging, independently of FIM scores. These findings should be integrated for correct neuropsychiatric assistance of COVID-19 patients in the subacute phase of the disease, and show the need for long-term psychological support and treatment of post-COVID-19 patients.
Ninety-one patients with cerebral lesions were tested on a task involving two conditions. In the first condition (response initiation) subjects were read a sentence from which the last word was omitted and were required to give a word which completed the sentence reasonably. In the second condition (response suppression) subjects were asked to produce a word unrelated to the sentence. Patients with frontal lobe involvement showed longer response latencies in the first condition and produced more words which were related to the sentence in the second, in comparison to patients with lesions elsewhere. Moreover, in the second condition patients with frontal lobe lesions produced fewer words which showed the use of a strategy during response preparation. Performance on the initiation and suppression conditions was unrelated at the group or single case level. The relationship between response initiation, suppression and strategy use are discussed.
Generalized anxiety disorder (GAD) is one of the most common mental disorders; however, there is no brief clinical measure for assessing GAD. The objective of this study was to develop a brief self-report scale to identify probable cases of GAD and evaluate its reliability and validity.
A criterion-standard study was performed in 15 primary care clinics in the United States from November 2004 through June 2005. Of a total of 2740 adult patients completing a study questionnaire, 965 patients had a telephone interview with a mental health professional within 1 week. For criterion and construct validity, GAD self-report scale diagnoses were compared with independent diagnoses made by mental health professionals; functional status measures; disability days; and health care use.
A 7-item anxiety scale (GAD-7) had good reliability, as well as criterion, construct, factorial, and procedural validity. A cut point was identified that optimized sensitivity (89%) and specificity (82%). Increasing scores on the scale were strongly associated with multiple domains of functional impairment (all 6 Medical Outcomes Study Short-Form General Health Survey scales and disability days). Although GAD and depression symptoms frequently co-occurred, factor analysis confirmed them as distinct dimensions. Moreover, GAD and depression symptoms had differing but independent effects on functional impairment and disability. There was good agreement between self-report and interviewer-administered versions of the scale.
The GAD-7 is a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research.
Background:
Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.
Methods:
We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating ("brain fog").
Results:
Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.
Conclusions:
Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).
Background and aims
Fatigue and neuropsychiatric (NP) symptoms are frequently observed in patients with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). This study aims to explore the relationship between clinical characteristics, inflammatory markers, and severity of fatigue and NP manifestations in COVID-19 survivors following the acute phase.
Methods
This cross-sectional study included adult participants who experienced any post-COVID NP symptoms. Questionnaires for fatigue (CFQ-11), anxiety-depression (DASS-21), insomnia (PSQI), cognitive impairment (ACE-III), and delayed processing speed (TMT-B) were administered. Demographic data, clinical characteristics of COVID-19 infection, and laboratory tests for inflammatory markers (CRP, IL-6, albumin, hemoglobin, and NL-ratio) were collected.
Results
The most common symptoms reported by 82 participants were fatigue (85.4%), insomnia (84.2%), anxiety (62.2%), subjective brain fog (61%), and depression (50%). There was no observed association between the severity of any target symptoms and the inflammatory markers. In multivariable analysis, a strong positive correlation was found between the number of PASC symptoms and the severity of fatigue, depression, anxiety, and sleep problems (p < 0.01). Those who had been infected more than once experienced more fatigue (p = 0.03). Patients with respiratory tract diseases were more likely to experience depression (p = 0.01), and smoking was associated with more sleep disturbances (p = 0.02). Lack of exercise was associated with slower processing speed (p = 0.02).
Conclusion
The severity of fatigue and NP symptoms of PASC is not correlated with changes in the inflammatory markers. However, certain clinical factors can predict the severity, including the number of PASC symptoms, frequency of COVID-19 infections, respiratory tract diseases, smoking, and exercise.
KEYWORDS:
COVID-19post-acute sequelae of COVID-19 (PASC)fatigueneuropsychiatric symptomsinflammatory markers
Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process. Long COVID is an often debilitating illness of severe symptoms that can develop during or following COVID-19. In this Review, Davis, McCorkell, Vogel and Topol explore our knowledge of long COVID and highlight key findings, including potential mechanisms, the overlap with other conditions and potential treatments. They also discuss challenges and recommendations for long COVID research and care.
Objective
Recent evidence suggests that patients suffering post-acute COVID syndrome frequently report cognitive complaints, but their characteristics and pathophysiology are unknown. This study aims to determine the characteristics of cognitive dysfunction in patients reporting cognitive complaints after COVID-19 and to evaluate the correlation between cognitive function and anxiety, depression, sleep, and olfactory function.
Methods
Cross-sectional study involving 50 patients with COVID-19 reporting cognitive complaints 9.12 ± 3.46 months after the acute infection. Patients were evaluated with a comprehensive neuropsychological protocol, and scales of fatigue, depression, anxiety, sleep and an olfactory test. Normative data and an age- and education matched healthy control group were used for comparison.
Results
COVID-19 patients showed a diminished performance on several tests evaluating attention and executive function, with alterations in processing speed, divided attention, selective attention, visual vigilance, intrinsic alertness, working memory, and inhibition; episodic memory; and visuospatial processing. Cognitive performance was correlated with olfactory dysfunction, and sleep quality and anxiety to a lesser extent, but not depression.
Conclusions
Patients with COVID-19 reporting cognitive symptoms showed a reduced cognitive performance, especially in the attention-concentration and executive functioning, episodic memory, and visuospatial processing domains. Future studies are necessary to disentangle the specific mechanisms associated with COVID-19 cognitive dysfunction.
Importance
COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome.
Objective
To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome.
Data Sources
Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists.
Study Selection
Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected.
Data Extraction & Synthesis
Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Turkey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model.
Main Outcomes & Measures
The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks after COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences of post-COVID-19 syndrome.
Results
The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I²=99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I²=98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals.
Conclusions & Relevance
A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena.
Study Registration
PROSPERO (CRD42021256965)
This cross-sectional study examines rates of cognitive impairment among patients who survived COVID-19 and whether the care setting was associated with cognitive impairment rates.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.
This study aims to evaluate the impacts of COVID-19 on cognitive functions in recovered patients and its relationship with inflammatory profiles. Twenty-nine patients recovered from COVID-19 as confirmed by negative nucleic tests for two consecutive times were recruited. A total of 29 age-, gender- and education-matched healthy controls were also recruited. The cognitive functions of all subjects were evaluated by the iPad-based online neuropsychological tests, including the Trail Making Test (TMT), Sign Coding Test (SCT), Continuous Performance Test (CPT), and Digital Span Test (DST). Blood samples from all patients were collected for examining inflammatory profiles, including interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and C-reactive protein (CRP). The relationship between cognitive functions and inflammatory profiles were analyzed by Pearson correlation. In results, although no significant differences were found in TMT, SCT, and DST between the two groups, patients with COVID-19 scored lower in the correct number of the second and third parts of CPT, they also scored higher in the missing number of the third part of CPT (all P < 0.05). In patients with COVID-19, there was a trend of significant difference for lower reaction time in the first and second parts of CPT (P = 0.050, and 0.051, respectively), as well as the lower correct number of the second part of CPT (P = 0.050). Correlation analysis showed that the reaction time for the first and second parts of CPT was positively correlated with the CRP levels (r = 0.557 and 0.410, P < 0.05). In conclusion, our findings indicated that cognitive impairments exist even in patients recovered from COVID-19, and might be possibly linked to the underlying inflammatory processes.
Background
Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain.
Methods
During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.
Findings
The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020. Data lock for this report was on April 26, 2020. During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies. Median patient age was 71 years (range 23–94; IQR 58–79). Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis. The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years.
Interpretation
To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy.
Funding
None.
Background/aims:
The aims of this study were to validate the newly developed version of the Addenbrooke's Cognitive Examination (ACE-III) against standardised neuropsychological tests and its predecessor (ACE-R) in early dementia.
Methods:
A total of 61 patients with dementia (frontotemporal dementia, FTD, n = 33, and Alzheimer's disease, AD, n = 28) and 25 controls were included in the study.
Results:
ACE-III cognitive domains correlated significantly with standardised neuropsychological tests used in the assessment of attention, language, verbal memory and visuospatial function. The ACE-III also compared very favourably with its predecessor, the ACE-R, with similar levels of sensitivity and specificity.
Conclusion:
The results of this study provide objective validation of the ACE-III as a screening tool for cognitive deficits in FTD and AD.
Sleep is not a single state, but a complex set of brain processes that supports several physiological needs. Sleep deprivation is known to affect attention in many animals, suggesting that a key function of sleep is to regulate attention. Conversely, tasks that require more attention drive sleep need and sleep intensity. Attention involves the ability to filter incoming stimuli based on their relative salience, and this is likely to require coordinated synaptic activity across the brain. This capacity may have only become possible with the evolution of related neural mechanisms that support two key sleep functions: stimulus suppression and synaptic plasticity. We argue here that sleep and attention may have coevolved as brain states that regulate each other.
Despite the prevalence of sleep complaints among psychiatric patients, few questionnaires have been specifically designed to measure sleep quality in clinical populations. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period with "good" sleepers (healthy subjects, n = 52) and "poor" sleepers (depressed patients, n = 54; sleep-disorder patients, n = 62). Acceptable measures of internal homogeneity, consistency (test-retest reliability), and validity were obtained. A global PSQI score greater than 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p less than 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.
A self-rating scale was developed to measure the severity of fatigue. Two-hundred and seventy-four new registrations on a general practice list completed a 14-item fatigue scale. In addition, 100 consecutive attenders to a general practice completed the fatigue scale and the fatigue item of the revised Clinical Interview Schedule (CIS-R). These were compared by the application of Relative Operating Characteristic (ROC) analysis. Tests of internal consistency and principal components analyses were performed on both sets of data. The scale was found to be both reliable and valid. There was a high degree of internal consistency, and the principal components analysis supported the notion of a two-factor solution (physical and mental fatigue). The validation coefficients for the fatigue scale, using an arbitrary cut off score of 3/4 and the item on the CIS-R were: sensitivity 75.5 and specificity 74.5.
We used functional magnetic resonance imaging to investigate brain activity while healthy subjects performed three different tasks, each of which alternated between: (i) phases relying on stimulus-oriented thought (i.e. cognitive processes provoked by incoming sensory information); and (ii) phases relying on stimulus-independent thought (i.e. cognitive processes that were not related to any information in the immediate sensory environment). Within each task, the two phases were matched as closely as possible. In all three tasks, lateral rostral prefrontal cortex was transiently activated by a switch between stimulus-oriented and stimulus-independent thought (regardless of the direction of the switch). Medial rostral prefrontal cortex consistently exhibited sustained activity for stimulus-oriented vs. stimulus-independent thought. These results suggest the involvement of rostral prefrontal cortex in selection between stimulus-oriented and stimulus-independent cognitive processes.
To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia.
Validation study.
A community clinic and an academic center.
Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC).
The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD.
Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively).
MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
Rostral prefrontal cortex (PFC) is a large brain region, and is unusually large in humans. Therefore, it seems likely that it might support functions that are central to cognition. However, until recently, almost nothing was known about what these functions might be. The 'gateway hypothesis' places these abilities at the centre of human mental processing. It maintains that rostral PFC supports mechanisms that enable us to attend, to a novel degree, either to environmental stimuli, or by contrast, to self-generated or maintained representations (i.e. the 'thoughts in our head'). In this way, investigations into the functions of rostral PFC will reveal key new insights into how human and non-human mental abilities differ.
The PHQ-9: validity of a brief depression severity measure