Physical Function and Association with Cognitive Function in Patients in a Post-COVID-19 Clinic-A Cross-Sectional Study.

Patients with long-term health sequelae of COVID-19 (post-COVID-19 condition) experience both physical and cognitive manifestations. However, there is still uncertainty about the prevalence of physical impairment in these patients and whether there is a link between physical and cognitive function. The aim was to assess the prevalence of physical impairment and investigate the association with cognition in patients assessed in a post-COVID-19 clinic. In this cross-sectional study, patients referred to an outpatient clinic ≥ 3 months after acute infection underwent screening of their physical and cognitive function as part of a comprehensive multidisciplinary assessment. Physical function was assessed with the 6-Minute Walk Test, the 30 s Sit-to-Stand Test and by measuring handgrip strength. Cognitive function was assessed with the Screen for Cognitive Impairment in Psychiatry and the Trail Making Test-Part B. Physical impairment was tested by comparing the patients' performance to normative and expected values. Association with cognition was investigated using correlation analyses and the possible explanatory variables regarding physical function were assessed using regression analyses. In total, we included 292 patients, the mean age was 52 (±15) years, 56% were women and 50% had been hospitalised during an acute COVID-19 infection. The prevalence of physical impairment ranged from 23% in functional exercise capacity to 59% in lower extremity muscle strength and function. There was no greater risk of physical impairment in previously hospitalised compared with the non-hospitalised patients. There was a weak to moderate association between physical and cognitive function. The cognitive test scores had statistically significant prediction value for all three outcomes of physical function. In conclusion, physical impairments were prevalent amongst patients assessed for post-COVID-19 condition regardless of their hospitalisation status and these were associated with more cognitive dysfunction.

Online Contingent Attention Training (OCAT): transfer effects to cognitive biases, rumination, and anxiety symptoms from two proof-of-principle studies.

The aim of the present research was to develop and test the efficacy of a novel online contingent attention training (i.e., OCAT) to modify attention and interpretation biases, improve emotion regulation, and reduce emotional symptom levels in the face of major stressors. Two proof-of-principle studies were carried out. In study 1, 64 undergraduates who were about to start a major stressful period (i.e., final exams) were randomized to undergo 10 days of active OCAT or a sham-control training. Emotion regulation (habitual use of rumination and reappraisal) and symptom levels (depression and anxiety) were assessed before and after the intervention. In study 2, the same 2 × 2 mixed design was used with 58 individuals from the general population undergoing a major stressful situation (the lockdown period at the beginning of the COVID-19 pandemic in 2020). In both studies, the OCAT group showed significant improvements on attention towards negative information and interpretation biases in comparison to the sham-control group. Additionally, changes in cognitive biases transferred to reductions of participants' use of rumination and anxiety symptom levels. These results show preliminary evidence regarding the efficacy of the OCAT to target attention and interpretation biases as well as to improve emotion regulation processes and to buffer against the effects of major stressors.

Evaluation of cognitive functions in adult individuals with COVID-19.

BACKGROUND AND PURPOSE: Cognitive deficits that are associated with coronavirus disease 2019 (COVID-19) and occur in the acute period are gaining importance. While most studies have focused on the elderly severely affected during acute infection, it remains unclear whether mild to moderate COVID-19 results in cognitive deficits in young patients. This study aims to evaluate the post-infection cognitive functions of young adults with mild to moderate symptoms of COVID-19. METHODS: A total of 100 adults with similar age and educational background were included in the study. Half of those had been infected with COVID-19 in the last 60 days (N = 50), and the other half had not (N = 50). Global cognitive skills of the participants were evaluated through Montreal Cognitive Assessment Scale (MoCA) and Clock-Drawing Test; memory functions with Öktem Verbal Memory Processes Test (Ö-VMPT); attention span with Digit Span Test; executive functions with Fluency Tests, Stroop Test, and Trail Making Test; visual perceptual skills with Rey Osterrieth Complex Figure Test (ROCF); and neuropsychiatric status with Neuropsychiatric Inventory (NPI). Evaluations were performed in the experimental group for 21 to 60 days from the onset of the disease, and throughout the study, in the control group. RESULTS: It was found that global cognitive skills, verbal memory, visual memory, executive function, and neuropsychiatric status were affected during COVID-19 (p < 0.05). CONCLUSION: When the cases were analyzed according to disease severity, no relationship was found between cognitive deficits and disease severity.

The therapeutic potential of non-invasive brain stimulation for the treatment of Long-COVID-related cognitive fatigue.

Following an acute COVID-19 infection, a large number of patients experience persisting symptoms for more than four weeks, a condition now classified as Long-COVID syndrome. Interestingly, the likelihood and severity of Long-COVID symptoms do not appear to be related to the severity of the acute COVID-19 infection. Fatigue is amongst the most common and debilitating symptoms of Long-COVID. Other symptomes include dyspnoea, chest pain, olfactory disturbances, and brain fog. Fatigue is also frequently reported in many other neurological diseases, affecting a broad range of everyday activities. However, despite its clinical significance, limited progress has been made in understanding its causes and developing effective treatment options. Non-invasive brain stimulation (NIBS) methods offer the unique opportunity to modulate fatigue-related maladaptive neuronal activity. Recent data show promising results of NIBS applications over frontoparietal regions to reduce fatigue symptoms. In this current paper, we review recent data on Long-COVID and Long-COVID-related fatigue (LCOF), with a special focus on cognitive fatigue. We further present widely used NIBS methods, such as transcranial direct current stimulation, transcranial alternating current stimulation, and transcutaneous vagus nerve stimulation and propose their use as possible therapeutic strategies to alleviate individual pathomechanisms of LCOF. Since NIBS methods are safe and well-tolerated, they have the potential to enhance the quality of life in a broad group of patients.

Cognitive deficit in post-acute COVID-19: an opportunity for EEG evaluation?

BACKGROUND AND PURPOSE: Among the most common post-COVID symptoms, many patients experienced subjective cognitive deficit, commonly named "brain fog," that might be present also in those individuals without severe acute COVID-19 respiratory involvement. Some studies have investigated some of the mechanisms that might be associated with the brain fog with objective techniques including transcranial magnetic stimulation and neuroimaging. METHODS: The aim of this study was to investigate the presence of electroencephalographic (EEG) alterations in people with post-COVID self-reported cognitive deficit. RESULTS: Out of the 90 patients attending the post-COVID neurology ambulatory service, twenty patients presenting brain fog at least 4 weeks after acute non-severe COVID-19 infection, and without previous history of epilepsy, were investigated with 19-channel EEG, Montreal Cognitive Assessment (MoCA), and magnetic resonance imaging (MRI). EEG was found altered in 65% of the sample, among which 69% presented a slowing activity and 31% were characterized by epileptic discharges principally in the frontal areas. None of the patients showed DWI MRI lesions. CONCLUSIONS: These findings highlight the usefulness of EEG analysis to objectively describe possible neurophysiological abnormalities in post-COVID patients presenting subjective cognitive deficit.

COVID-19 infection does not seem to affect cognition in college students.

Emerging evidence indicates that COVID-19 damages the central nervous system and thereby might engender long-term cognitive impairment. Self-reports and some measures of cognitive ability suggest that long COVID can lead to substantial and frightening detriments in cognition. To further explore this issue, we used data from university courses on cognitive psychology where students participated in classic experiments that measure various aspects of cognition. Across 24 experiments we compared cognitive performance of students who had contracted COVID-19 against those who were uninfected. Using Bayes Factor analyses, we assessed both differences and invariances in performance as a function of infection status. Our findings suggest that COVID-19 infection has hardly any impact on cognition for university students.

The Coronavirus Footprint on Dual-Task Performance in Post-Acute Patients after Severe COVID-19: A Future Challenge for Rehabilitation.

Recent studies suggest that also the non-critical form of COVID-19 infection may be associated with executive function impairments. However, it is not clear if they result from cognitive impairments or by COVID-19 infection per se. We aimed to investigate if patients in the post-acute stage of severe COVID-19 (PwCOVID), without manifest cognitive deficits, reveal impairments in performing dual-task (DT) activities compared to healthy controls (HS). We assessed balance in 31 PwCOVID vs. 30 age-matched HS by stabilometry and the Timed Up and Go (TUG) test with/without a cognitive DT. The DT cost (DTC), TUG test time and sway oscillations were recorded; correct cognitive responses (CCR) were calculated to evaluate cognitive performance. Results show a significant difference in overall DT performance between PwCOVID and HS in both stabilometry (p < 0.01) and the TUG test (p < 0.0005), although with similar DTCs. The main difference in the DTs between groups emerged in the CCR (effect size > 0.8). Substantially, PwCOVID gave priority to the motor task, leaving out the cognitive one, while HS performed both tasks simultaneously. Our findings suggest that PwCOVID, even without a manifest cognitive impairment, may present a deficit in executive function during DTs. These results encourage the use of DTs and CCR in PwCOVID.

Virtual individual cognitive stimulation therapy in Hong Kong: A mixed methods feasibility study.

OBJECTIVES: We aimed to translate and culturally adapt Virtual Individual Cognitive Stimulation Therapy (V-iCST) for the Hong Kong (HK) Chinese population, and to evaluate its feasibility and acceptability. METHODS: A mixed methods case series (N=8) was used to assess the feasibility of V-iCST and changes in cognition, quality of life (QoL), mood, and communication pre and post-test. Data were analyzed with the reliable change index. Thematic analysis of post-therapy interviews and content analysis of session rating forms were used to evaluate the acceptability. RESULTS: V-iCST was feasible with low attrition (0%) and high attendance (100%). Participants had reliable improvements in all outcomes. Six had improved and stable cognition; four had clinically significant changes in depression. There were no reliable changes in QoL. Qualitative analyses indicated V-iCST as acceptable but required assistance. CONCLUSIONS: V-iCST can be adapted for HK Chinese with dementia and potentially improve cognition, QoL, mood, and communication.

Fecal microbiota transplant improves cognition in hepatic encephalopathy and its effect varies by donor and recipient.

Early data suggest fecal microbiota transplant (FMT) may treat hepatic encephalopathy (HE). Optimal FMT donor and recipient characteristics are unknown. We assessed the safety and efficacy of FMT in patients with prior overt HE, comparing five FMT donors. We performed an open-label study of FMT capsules, administered 5 times over 3 weeks. Primary outcomes were change in psychometric HE score (PHES) and serious adverse events (SAEs). Serial stool samples underwent shallow shotgun metagenomic sequencing. Ten patients completed FMT administration and 6-month follow-up. Model for End-Stage Liver Disease (MELD) score did not change after FMT (14 versus 14, p = 0.51). Thirteen minor adverse events and three serious adverse events (two unrelated to FMT) were reported. One SAE was extended-spectrum beta-lactamase Escherichia coli bacteremia. The PHES improved after three doses of FMT (+2.1, p < 0.05), after five doses of FMT (+2.9, p = 0.007), and 4 weeks after the fifth dose of FMT (+3.1, p = 0.02). Mean change in the PHES ranged from -1 to +6 by donor. Two taxa were identified by random forest analysis and confirmed by linear regression to predict the PHES- Bifidobacterium adolescentis (adjusted R2 = 0.27) and B. angulatum (adjusted R2 = 0.25)-both short-chain fatty acid (SCFA) producers. Patients who responded to FMT had higher levels of Bifidobacterium as well as other known beneficial taxa at baseline and throughout the study. The FMT donor with poorest cognitive outcomes in recipients had the lowest fecal SCFA levels. Conclusion: FMT capsules improved cognition in HE, with an effect varying by donor and recipient factors (NCT03420482).

Effects of Two Short-Term Aerobic Exercises on Cognitive Function in Healthy Older Adults during COVID-19 Confinement in Japan: A Pilot Randomized Controlled Trial.

Aerobic exercise improves executive function-which tends to decline with age-and dual-task training with aerobic exercise improves the global cognitive function. However, home-based older adults could not follow these programs due to social isolation during the coronavirus disease 2019 pandemic. Therefore, we conducted a single-blind randomized controlled trial with 88 healthy older adults without dementia or sarcopenia who were randomly assigned into the Nordic walking (aerobic exercise), dance (dual-task training with aerobic exercise), or control group. The participants in both exercise intervention groups trained for 30 min, three times per week, for 4 weeks. All groups consumed amino acid-containing foods three times per week. We found that both exercise intervention groups showed improvements in executive function, while the dance group showed additional improvement in global cognitive function. The dance group showed a higher maximum gait speed, greater improvement in imitation ability, and improved executive function and cognitive function than the Nordic walking group. The intervention programs did not significantly affect the muscle mass or muscle output than the control group; however, both programs improved the participant neurological functions such as the heel lift, with dance training being the most effective intervention. In conclusion, dance training effectively improves cognitive function.

Impact of active and latent concerns about COVID-19 on attention.

The interactions between emotion and attention are complex due to the multifaceted nature of attention. Adding to this complexity, the COVID-19 pandemic has altered the emotional landscape, broadly heightening health and financial concerns. Can the heightened concerns about COVID-19 impair one or more of the components of attention? To explore the connection between heightened concerns about COVID-19 and attention, in a preregistered study, we collected survey responses from 234 participants assessing levels of concerns surrounding COVID-19, followed by four psychophysics tasks hypothesized to tap into different aspects of attention: visual search, working memory, sustained attention, and cognitive control. We also measured task-unrelated thoughts. Results showed that task-unrelated thoughts, but not survey reports of concern levels, negatively correlated with sustained attention and cognitive control, while visual search and working memory remained robust to task-unrelated thoughts and survey-indicated concern levels. As a whole, these findings suggest that being concerned about COVID-19 does not interfere with cognitive function unless the concerns are active in the form of task-unrelated thoughts.

Trends in Cognitive Function Among Chinese Elderly From 1998 to 2018: An Age-Period-Cohort Analysis.

Objectives: To investigate the effects of age, period, and cohort (APC) on trends in cognitive function among the Chinese elderly, and to explore how gender gaps in cognitive function change with age, period, and cohort. Methods: This study used data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2018, and included 90,432 participants aged above 65 years old. The measurement of cognitive function was the score of the Mini-Mental State Examination (MMSE). Cross-classified random-effect models were used to investigate age, period, and cohort trends in cognitive function. Results: Mini-Mental State Examination scores decreased with age at an increasing rate. While the cohort effect was nearly stable, the period effect demonstrated a downward trend from 1998 to 2002 followed by a nearly flat line. Females were associated with lower MMSE scores than males. When age increased, the gender gaps in MMSE scores further increased. The period-based gender gaps in MMSE scores diverged throughout the 20 years, while the cohort-based gender disparities in MMSE scores converged with successive cohorts. Conclusions: Age, period, and cohort had different and independent effects on cognitive function among the Chinese elderly. The effect of age was stronger than that of period and cohort. Gender disparities in cognitive function increased with age and period, and decreased with successive cohorts.

Cognitive dysfunction associated with COVID-19: A comprehensive neuropsychological study.

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.

Neuropsychological deficits in patients with cognitive complaints after COVID-19.

BACKGROUND: While much of the scientific focus thus far has been on cognitive sequelae in patients with severe COVID-19, subjective cognitive complaints are being reported across the spectrum of disease severity, with recent studies beginning to corroborate patients' perceived deficits. In response to this, the aims of this study were to (1) explore the frequency of impaired performance across cognitive domains in post-COVID patients with subjective complaints and (2) uncover whether impairment existed within a single domain or across multiple. METHODS: Sixty-three patients with subjective cognitive complaints post-COVID were assessed with a comprehensive protocol consisting of various neuropsychological tests and mood measures. Cognitive test performance was transformed into T scores and classified based on recommended guidelines. After performing a principal component analysis to define cognitive domain factors, distributions of test scores within and across domains were analyzed. RESULTS: Results revealed pervasive impact on attention abilities, both as the singularly affected domain (19% of single-domain impairment) as well as coupled with decreased performance in executive functions, learning, and long-term memory. These salient attentional and associated executive deficits were largely unrelated to clinical factors such as hospitalization, disease duration, biomarkers, or affective measures. DISCUSSION: These findings stress the importance of comprehensive evaluation and intervention to address cognitive sequelae in post-COVID patients of varying disease courses, not just those who were hospitalized or experienced severe symptoms. Future studies should investigate to what extent these cognitive abilities are recuperated over time as well as employ neuroimaging techniques to uncover underlying mechanisms of neural damage.

Risk factors and abnormal cerebrospinal fluid associate with cognitive symptoms after mild COVID-19.

Cognitive post-acute sequelae of SARS-CoV-2 (PASC) can occur after mild COVID-19. Detailed clinical characterizations may inform pathogenesis. We evaluated 22 adults reporting cognitive PASC and 10 not reporting cognitive symptoms after mild SARS-CoV-2 infection through structured interviews, neuropsychological testing, and optional cerebrospinal fluid (CSF) evaluations (53%). Delayed onset of cognitive PASC occurred in 43% and associated with younger age. Cognitive PASC participants had a higher number of pre-existing cognitive risk factors (2.5 vs. 0; p = 0.03) and higher proportion with abnormal CSF findings (77% vs. 0%; p = 0.01) versus controls. Cognitive risk factors and immunologic mechanisms may contribute to cognitive PASC pathogenesis.

Information and communication technologies for the improvement of cognitive function in healthy older adults: a systematic review protocol.

INTRODUCTION: Mild cognitive impairment is one of the consequences of ageing, causing functional disability, a poor quality of life and an increased socioeconomic expenditure. Evidence shows that patients go through a long preclinical stage in which cognitive deficits appear subtly until they reach the threshold of dementia. Non-pharmacological interventions have been gaining ground as prevention of modifiable factors of cognitive decline such as obesity, diabetes, physical inactivity or social isolation. Along these lines, Information and Communication Technologies (ICTs) can be a tool for cognitive stimulation, cognitive training and cognitive rehabilitation. The main objective of the systematic review will be to review and analyse the use of ICTs for the improvement of cognitive functions in healthy older adult population aged 50 and over, for the prevention of cognitive impairment METHODS: A systematic review will be conducted including randomised clinical trials in adults without diseases or accidents associated with cognitive impairment, and whom have used ICTs for the improvement of cognitive functions between 2010 and 2020 in English or Spanish. The articles that report data on cognitive function by domain, for example, memory or executive functions, or by test will be included. The databases Medline (PubMed), CinahlPlus, Scopus, ISI WoS, CENTRAL and IEEE Xplore will be searched. Studies that meet the inclusion criteria will be analysed according to the Cochrane RoB2 tool for risk of bias assessment. ETHICS AND DISSEMINATION: Ethical approval is not necessary as this is a systematic review. The results will be published in scientific journals, as well as in specialised congresses on the subject of study.

Staying informed without a cost: No effect of positive news media on stress reactivity, memory and affect in young adults.

INTRODUCTION: We read, see and hear news from various media sources every day. A large majority of the news is negative. A previous study from our laboratory showed that reading negative news is associated with both increased stress reactivity (measured via the stress hormone cortisol) and recall of the negative news segments in women. OBJECTIVES: The present study investigated the effects of positive news on cortisol stress reactivity, memory and affect using a methodology highly similar to the study on negative news that was previously used by our team. METHODS: Sixty-two healthy participants aged between 18 and 35 years (81% women) were randomly exposed to either positive or neutral news segments, followed by a laboratory stressor. We assessed participants' affect three times during the procedure and measured cortisol in saliva eight times (at 10-minute intervals). Twenty-four hours later, participants were contacted by phone to assess their recall of the news segments. RESULTS: Results showed that exposure to positive news, relative to neutral news, did not modulate participants' cortisol levels in response to the laboratory stressor. Positive news had no impact on memory recall of the news and did not change participants' positive or negative affect. Bayes factors suggested that these nonsignificant results are not attributable to low statistical power. CONCLUSION: Contrary to negative news, positive and neutral news do not modulate stress reactivity, memory and affect. These results suggest that people can stay informed without physiological and psychological costs when the news to which they are exposed adopt a positive or neutral approach.

A Novel Phenylpyrrolidine Derivative: Synthesis and Effect on Cognitive Functions in Rats with Experimental Ishemic Stroke.

We performed an in silico, in vitro, and in vivo assessment of a potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (compound 1) as a potential prodrug for cognitive function improvement in ischemic brain injury. Using in silico methods, we predicted the pharmacological efficacy and possible safety in rat models. In addition, in silico data showed neuroprotective features of compound 1, which were further supported by in vitro experiments in a glutamate excitotoxicity-induced model in newborn rat cortical neuron cultures. Next, we checked whether compound 1 is capable of crossing the blood-brain barrier in intact and ischemic animals. Compound 1 improved animal behavior both in intact and ischemic rats and, even though the concentration in intact brains was low, we still observed a significant anxiety reduction and activity escalation. We used molecular docking and molecular dynamics to support our hypothesis that compound 1 could affect the AMPA receptor function. In a rat model of acute focal cerebral ischemia, we studied the effects of compound 1 on the behavior and neurological deficit. An in vivo experiment demonstrated that compound 1 significantly reduced the neurological deficit and improved neurological symptom regression, exploratory behavior, and anxiety. Thus, here, for the first time, we show that compound 1 can be considered as an agent for restoring cognitive functions.