Background: There is growing concern about possible cognitive consequences of COVID-19, with reports of 'Long COVID' symptoms persisting into the chronic phase and case studies revealing neurological problems in severely affected patients. However, there is little information regarding the nature and broader prevalence of cognitive problems post-infection or across the full spread of disease severity.

Methods: We sought to confirm whether there was an association between cross-sectional cognitive performance data from 81,337 participants who between January and December 2020 undertook a clinically validated web-optimized assessment as part of the Great British Intelligence Test, and questionnaire items capturing self-report of suspected and confirmed COVID-19 infection and respiratory symptoms.

Findings: People who had recovered from COVID-19, including those no longer reporting symptoms, exhibited significant cognitive deficits versus controls when controlling for age, gender, education level, income, racial-ethnic group, pre-existing medical disorders, tiredness, depression and anxiety. The deficits were of substantial effect size for people who had been hospitalised ( = 192), but also for non-hospitalised cases who had biological confirmation of COVID-19 infection ( = 326). Analysing markers of premorbid intelligence did not support these differences being present prior to infection. Finer grained analysis of performance across sub-tests supported the hypothesis that COVID-19 has a multi-domain impact on human cognition.

Interpretation: Interpretation. These results accord with reports of 'Long Covid' cognitive symptoms that persist into the early-chronic phase. They should act as a clarion call for further research with longitudinal and neuroimaging cohorts to plot recovery trajectories and identify the biological basis of cognitive deficits in SARS-COV-2 survivors.

Funding: Funding. AH is supported by the UK Dementia Research Institute Care Research and Technology Centre and Biomedical Research Centre at Imperial College London. WT is supported by the EPSRC Centre for Doctoral Training in Neurotechnology. SRC is funded by a Wellcome Trust Clinical Fellowship 110,049/Z/15/Z. JMB is supported by Medical Research Council (MR/N013700/1). MAM, SCRW and PJH are, in part, supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.

Background And Purpose: Many COVID-19 patients report persistent symptoms, including cognitive disturbances. We performed a scoping review on this topic, focusing primarily on cognitive manifestations.

Methods: Abstracts and full texts of studies published on PubMed (until May 2023) addressing cognitive involvement persisting after SARS-CoV-2 infection were reviewed, focusing on terms used to name the cognitive syndrome, reported symptoms, their onset time and duration, and testing batteries employed. Reported psychiatric symptoms, their assessment tools, and more general manifestations were also extracted.

Results: Among the 947 records identified, 180 studies were included. Only one third of them used a label to define the syndrome. A minority of studies included patients according to stringent temporal criteria of syndrome onset (34%), whereas more studies reported a minimum required symptom duration (77%). The most frequently reported cognitive symptoms were memory and attentional-executive disturbances, and among psychiatric complaints, the most frequent were anxiety symptoms, depression, and sleep disturbances. Most studies reported fatigue among general symptoms. Thirty-six studies employed cognitive measures: screening tests alone (n = 19), full neuropsychological batteries (n = 25), or both (n = 29); 30 studies performed psychiatric testing. Cognitive deficits were demonstrated in 39% of subjects, the most frequently affected domains being attention/executive functions (90%) and memory (67%).

Conclusions: Currently, no agreement exists on a label for post-COVID-19 cognitive syndrome. The time of symptom onset after acute infection and symptom duration are still discussed. Memory and attention-executive complaints and deficits, together with fatigue, anxiety, and depression symptoms, are consistently reported, but the objective evaluation of these symptoms is not standardized.

COVID-19 was primarily considered a pulmonary disease with extrapulmonary manifestations. As the pandemic spread, there has been growing evidence that the disease affects various organs/systems, including the central and peripheral nervous systems. Accumulation of clinical data demonstrates that in a large population of survivors impairments in the function of one or more organs may persist for a long time, a phenomenon commonly known as post COVID or long COVID. Fatigue and cognitive dysfunction, such as concentration problems, short-term memory deficits, general memory loss, a specific decline in attention, language and praxis abilities, encoding and verbal fluency, impairment of executive functions, and psychomotor coordination, are amongst the most common and debilitating features of neuropsychatric symptoms of post COVID syndrome. Several patients also suffer from compromised sleep, depression, anxiety and post-traumatic stress disorder. Patients with long COVID may demonstrate brain hypometabolism, hypoperfusion of the cerebral cortex and changes in the brain structure and functional connectivity. Children and adolescents represent a minority of COVID-19 cases, so not surprisingly data on the long-term sequelae after SARS-CoV-2 infections in these age groups are scarce. Although the pathogenesis, clinical characteristics, epidemiology, and risk factors of the acute phase of COVID-19 have been largely explained, these areas are yet to be explored in long COVID. This review aims to provide an update on what is currently known about long COVID effects on mental health.

Introduction: There have been more than 425 million COVID-19 infections worldwide. Post-COVID illness has become a common, disabling complication of this infection. Therefore, it presents a significant challenge to global public health and economic activity.

Methods: Comprehensive clinical assessment (symptoms, WHO performance status, cognitive testing, CPET, lung function, high-resolution CT chest, CT pulmonary angiogram and cardiac MRI) of previously well, working-age adults in full-time employment was conducted to identify physical and neurocognitive deficits in those with severe or prolonged COVID-19 illness.

Results: 205 consecutive patients, age 39 (IQR30.0-46.7) years, 84% male, were assessed 24 (IQR17.1-34.0) weeks after acute illness. 69% reported ≥3 ongoing symptoms. Shortness of breath (61%), fatigue (54%) and cognitive problems (47%) were the most frequent symptoms, 17% met criteria for anxiety and 24% depression. 67% remained below pre-COVID performance status at 24 weeks. One third of lung function tests were abnormal, (reduced lung volume and transfer factor, and obstructive spirometry). HRCT lung was clinically indicated in <50% of patients, with COVID-associated pathology found in 25% of these. In all but three HRCTs, changes were graded 'mild'. There was an extremely low incidence of pulmonary thromboembolic disease or significant cardiac pathology. A specific, focal cognitive deficit was identified in those with ongoing symptoms of fatigue, poor concentration, poor memory, low mood, and anxiety. This was notably more common in patients managed in the community during their acute illness.

Conclusion: Despite low rates of residual cardiopulmonary pathology, in this cohort, with low rates of premorbid illness, there is a high burden of symptoms and failure to regain pre-COVID performance 6-months after acute illness. Cognitive assessment identified a specific deficit of the same magnitude as intoxication at the UK drink driving limit or the deterioration expected with 10 years ageing, which appears to contribute significantly to the symptomatology of long-COVID.

Background: A considerable proportion of people experience lingering symptoms after Coronavirus Disease 2019 (COVID-19). The aim of this study was to investigate the frequency, pattern and functional implications of cognitive impairments in patients at a long-COVID clinic who were referred after hospitalisation with COVID-19 or by their general practitioner.

Methods: Patients underwent cognitive screening and completed questionnaires regarding subjective cognition, work function and quality of life. Patients' cognitive performance was compared with that of 150 age-, sex-, and education-matched healthy controls (HC) and with their individually expected performance calculated based on their age, sex and education.

Results: In total, 194 patients were assessed, on average 7 months (standard deviation: 4) after acute COVID-19.44-53 % of the patients displayed clinically relevant cognitive impairments compared to HC and to their expected performance, respectively. Moderate to large impairments were seen in global cognition and in working memory and executive function, while mild to moderate impairments occurred in verbal fluency, verbal learning and memory. Hospitalised (n = 91) and non-hospitalised (n = 103) patients showed similar degree of cognitive impairments in analyses adjusted for age and time since illness. Patients in the cognitively impaired group were older, more often hospitalised, had a higher BMI and more frequent asthma, and were more often female. More objective cognitive impairment was associated with more subjective cognitive difficulties, poorer work function and lower quality of life.

Limitations: The study was cross-sectional, which precludes causality inferences.

Conclusions: These findings underscore the need to assess and treat cognitive impairments in patients at long-COVID clinics.

Background And Purpose: Cognitive decline is a recognized manifestation of long COVID, even among patients who experience mild disease. However, there is no evidence regarding the length of cognitive decline in these patients. This study aimed to assess whether COVID-19-related cognitive decline is a permanent deficit or if it improves over time.

Methods: Cognitive performance was evaluated by means of the Montreal Cognitive Assessment (MoCA) in COVID-19 survivors and noninfected individuals. All study participants had four cognitive evaluations, two of them before the pandemic and the other two, 6 and 18 months after the initial SARS-CoV-2 outbreak infection in the village. Linear mixed effects models for longitudinal data were fitted to assess differences in cognitive performance across COVID-19 survivors and noninfected individuals.

Results: The study included 78 participants, 50 with history of mild COVID-19 and 28 without. There was a significant-likely age-related-decline in MoCA scores between the two prepandemic tests (β = -1.53, 95% confidence interval [CI] = -2.14 to -0.92, p < 0.001), which did not differ across individuals who later developed COVID-19 when compared to noninfected individuals. Six months after infection, only COVID-19 survivors had a significant decline in MoCA scores (β = -1.37, 95% CI = -2.14 to -0.61, p < 0.001), which reversed after 1 additional year of follow-up (β = 0.66, 95% CI = -0.11 to 1.42, p = 0.092). No differences were noticed among noninfected individuals when both postpandemic MoCA scores were compared.

Conclusions: Study results suggest that long COVID-related cognitive decline may spontaneously improve over time.

As the heterogeneity of symptoms is increasingly recognized among long-COVID patients, it appears highly relevant to study potential pathophysiological differences along the different subtypes. Preliminary evidence suggests distinct alterations in brain structure and systemic inflammatory patterns in specific groups of long-COVID patients. To this end, we analyzed differences in cortical thickness and peripheral immune signature between clinical subgroups based on 3 T-MRI scans and signature inflammatory markers in n = 120 participants comprising healthy never-infected controls (n = 30), healthy COVID-19 survivors (n = 29), and subgroups of long-COVID patients with (n = 26) and without (n = 35) cognitive impairment according to screening with Montreal Cognitive Assessment. Whole-brain comparison of cortical thickness between the 4 groups was conducted by surface-based morphometry. We identified distinct cortical areas showing a progressive increase in cortical thickness across different groups, starting from healthy individuals who had never been infected with COVID-19, followed by healthy COVID-19 survivors, long-COVID patients without cognitive deficits (MoCA ≥ 26), and finally, long-COVID patients exhibiting significant cognitive deficits (MoCA < 26). These findings highlight the continuum of cortical thickness alterations associated with COVID-19, with more pronounced changes observed in individuals experiencing cognitive impairment (p < 0.05, FWE-corrected). Affected cortical regions covered prefrontal and temporal gyri, insula, posterior cingulate, parahippocampal gyrus, and parietal areas. Additionally, we discovered a distinct immunophenotype, with elevated levels of IL-10, IFNγ, and sTREM2 in long-COVID patients, especially in the group suffering from cognitive impairment. We demonstrate lingering cortical and immunological alterations in healthy and impaired subgroups of COVID-19 survivors. This implies a complex underlying pathomechanism in long-COVID and emphasizes the necessity to investigate the whole spectrum of post-COVID biology to determine targeted treatment strategies targeting specific sub-groups.

Background: Despite the prevalence of cognitive impairment poststroke, there is uncertainty regarding interventions to improve cognitive function poststroke. This systematic review and meta-analysis evaluate the effectiveness of rehabilitation interventions across multiple domains of cognitive function.

Methods: Five databases were searched from inception to August 2019. Eligible studies included randomized controlled trials of rehabilitation interventions for people with stroke when compared with other active interventions or standard care where cognitive function was an outcome.

Results: Sixty-four randomized controlled trials (n=4005 participants) were included. Multiple component interventions improved general cognitive functioning (MD, 1.56 [95% CI, 0.69-2.43]) and memory (standardized MD, 0.49 [95% CI, 0.27-0.72]) compared with standard care. Physical activity interventions improved neglect (MD, 13.99 [95% CI, 12.67-15.32]) and balance (MD, 2.97 [95% CI, 0.71-5.23]) compared with active controls. Noninvasive brain stimulation impacted neglect (MD, 20.79 [95% CI, 14.53-27.04) and functional status (MD, 14.02 [95% CI, 8.41-19.62]) compared with active controls. Neither cognitive rehabilitation (MD, 0.37 [95% CI, -0.94 to 1.69]) nor occupational-based interventions (MD, 0.45 [95% CI, -1.33 to 2.23]) had a significant effect on cognitive function compared with standard care.

Conclusions: There is some evidence to support multiple component interventions, physical activity interventions, and noninvasive brain stimulation improving cognitive function poststroke. Findings must be interpreted with caution given the overall moderate to high risk of bias, heterogeneity of interventions, and outcome measures across studies.

Background: Cognition affects poststroke recovery, but meta-analyses of cognition have not yet provided a comparison of observational and intervention evidence.

Objective: To describe the trajectory of poststroke cognition and the factors that moderate it across intervention and observational cohorts.

Methods: Six databases were searched up to January 2020. Studies describing quantitative changes in cognition in adults poststroke were included. Interventions were classified into pharmacological, therapist-led, nonroutine/alternative, and usual care. Summary estimates were compared via hierarchical mixed-effects models. Age, recovery stage, stroke etiology, cognitive domain targeted in studies, and intervention types were investigated as moderators of cognition. Recovery stage and intervention were further analyzed in a multiplicative metaregression model.

Results: A total of 43 intervention trials and 79 observation cohorts involving 28 222 stroke participants were included. Heterogeneity was significant (τ = 0.09; CI = 0.01-0.21, < .001) with no evidence of publication bias. Cognitive recovery was greater in intervention trials ( = 0.47; CI = 0.37-0.58) than observational cohorts ( = 0.28; CI = 0.20-0.36) across all moderators analyzed. Nonroutine/alternative and pharmacological trials achieved the best overall results ( = 0.57, CI = 0.42-0.73, and = 0.52, CI = 0.30-0.74, respectively), followed by therapist-led ( = 0.46; CI = 0.17-0.74), and usual care ( = 0.28; CI = 0.11-0.45) interventions. Medium recovery effects (ie, ≥ 0.5) were observed in examining first-ever stroke, executive function, visuo-perceptual, consciousness, and psychomotor skills, 61 to 180 days poststroke, in participants aged 65 to 70 years.

Conclusion: Cognitive recovery is possible using different controlled interventions in all recovery stages, with smaller benefits ≥2 years poststroke. Longer-term studies are needed to determine the role of nonroutine/alternative therapies and the association between cognitive recovery and performance in everyday activities.

Drug addiction is a chronic and relapsing disorder in which repeated drug exposure compromises brain neuroplasticity. Brain areas normally involved in learning and goal-directed behaviors become corrupted, which may lead to cognitive deficits that coexist with other addiction symptoms and predict a worse treatment outcome. New learning experiences that are not motivated by drugs may improve both cognitive deficits and drug-induced symptoms by promoting adaptive neuroplastic changes that could alleviate or reverse those involved in addiction. The present review will focus on whether potentiating healthy cognitive function, either by formal cognitive training or non-drug related environmental experiences, could exert beneficial effects in the therapeutics of addiction. Although additional studies are needed, the available clinical and preclinical evidence suggests that cognitive stimulation may provide a valuable adjuvant intervention in drug addiction.

Cognitive remediation is currently recommended to treat cognitive and functional impairments in patients with schizophrenia. Recently, treatment of negative symptoms has been proposed as a new target for cognitive remediation. Evidence of reductions in negative symptoms has been described in different meta-analyses. However, treating primary negative symptoms is still an open question. Despite some emerging evidence, more research focused on individuals with primary negative symptoms is indispensable. In addition, more attention to the role of moderators and mediators and the use of more specific assessments is necessary. Nevertheless, cognitive remediation could be considered as one promising option to treat primary negative symptoms.