Martina Vanova

Importance: Cognitive impairment is common in long COVID and severely affects daily life, with no proven treatments to date. Objective: To evaluate the ability of cognitive rehabilitation (CR) to improve goal attainment, cognitive, and clinical outcomes in individuals with cognitive impairment as part of long COVID. Design, Setting, and Participants: This multicenter, single-blind, 2-arm, parallel-group randomized clinical trial was conducted at 3 sites in England between February 2023 and March 2024. Participants were adults aged 30 to 60 years with prior COVID-19 infection and objective cognitive impairment (≥1 SD below age norm in ≥2 cognitive domains). A sample size of 88 participants (44:44) was required to detect a conservative effect of 0.7 on the goal attainment score at 3 months. Interventions: Participants were randomized (1:1) to CR or treatment as usual (TAU). CR consisted of 10 individual 1-hour sessions conducted once per week with a trained researcher, applying evidence-based strategies to 3 individually selected, personally meaningful functional goals. TAU was variable, with most participants having access to specialist memory clinics. Main Outcome and Measures: The primary outcome consisted of participant-reported goal-attainment scores at 3 months after randomization measured by the Bangor Goal-Setting Interview. Analysis was conducted on an intention-to-treat basis using multilevel mixed-effects models with 2-sided 95% CIs and 5% significance. Results: A total of 78 participants (24 male [30.8%] and 54 female [69.2%]; mean [SD] age, 47.3 [7.2] years) were randomized, including 38 individuals in CR and 40 individuals in TAU groups. At 3 months after randomization, goal attainment was significantly greater in the CR compared with the TAU group (adjusted mean difference, 2.88 [95% CI, 2.03-3.73]; P < .001; Cohen d = 1.57), with CR providing a large and clinically meaningful treatment effect. This was sustained at 6 months, with a lower effect size (adjusted mean difference, 1.72 [95% CI, 0.86-2.57]; P < .001; Cohen d = 0.91). Conclusions and relevance: In this study, individualized, goal-oriented CR led to significant and sustained improvements in goal attainment in people with long COVID–related cognitive impairment. These findings may guide and inform the provision of CR treatments and services for people living with long COVID. Trial Registration: ClinicalTrials.gov Identifier: NCT05731570

Introduction: There is an ongoing debate about the neural mechanisms and subjective preferences involved in the processing of social rewards compared to non‐social reward types. Methods: Using whole‐brain functional magnetic resonance imaging (fMRI), we examined brain activation patterns during the anticipation and consumption phases of monetary and social rewards (using the Monetary and Social Incentive Delay Task—MSIDT, featuring human avatars) and their associations with self‐reported social reward preferences measured by the Social Reward Questionnaire (SRQ) in 20 healthy right‐handed individuals. Results: In the anticipation phase, all reward types activated the dorsal striatum, middle cingulo‐insular (salience) network, inferior frontal gyrus (IFG), and supplementary motor areas. The consumption phase primarily engaged posterior cortical areas. Higher preference for prosocial interactions (as assessed by SRQ) was associated with increased right posterior cingulate activity during monetary reward anticipation and enhanced activity in the left striatum and salience network activation during social reward anticipation. In the consumption phase, higher prosociality was associated with stronger activation in frontal regions, the dorsal striatum, and the thalamus for monetary rewards and stronger putamen activity for social rewards. Conclusions: Individual differences in social reward preferences, particularly prosocial tendencies, are associated with distinct neural activations during reward processing. These findings have potential implications for understanding altered reward processing in clinical populations.

Background: Between 25 and 75% of people with persistent post-acute sequelae of SARS-CoV-2 infection (PASC) experience cognitive difficulties, compromising functional ability, quality of life, and activities of daily living, including work. Despite this significant morbidity, there is a paucity of interventions for this disorder that have undergone evaluation within a formal trial setting. Therefore, we have developed a cognitive rehabilitation programme, specifically designed to address the cognitive symptoms of PASC, notably impaired attention and processing speed, while also accounting for other PASC symptoms (fatigue, post-exertional malaise) that may aggravate the cognitive impairment. This study protocol outlines a randomised controlled trial (RCT) designed to evaluate the effectiveness of this programme compared to standard clinical care. Methods: This is a multi-centre, parallel-group, individually randomised controlled trial, comparing standard clinical care with and without cognitive rehabilitation. We will recruit 120 non-hospitalised adults (aged 30–60 years) from three NHS sites in England with a history of COVID-19 infection and cognitive impairment persisting more than 3 months after the acute infection. Participants will be randomised (1:1) to the intervention or control groups, with the latter represented as a provision of standard clinical care without cognitive rehabilitation. The cognitive rehabilitation programme consists of ten 1-hour sessions, delivered weekly. Outcomes will be collected at baseline, 3, and 6 months, with participant-defined goal-attainment scores, relating to functional goals, at 3 months as the primary outcome measure. Secondary outcomes will be cognitive function, measures of quality of life, social functioning, mental health, fatigue, sleep, post-exertional malaise, and social and health care service use. We will also evaluate the health-economic benefits of cognitive rehabilitation in this population. Discussion: Cognitive impairment in PASC is a major cause of functional disability with no effective treatment. Accordingly, we will undertake an RCT of cognitive rehabilitation, the protocol of which is published here. If this trial is successful in delivering improvements in trial outcomes, it will address a major unmet need relating to this emergent disorder, with a significant impact on affected individuals and the wider health economy. Trial registration: ClinicalTrials.gov NCT05731570. Registered on February 16, 2023

Background Between 25–75% of people with persistent post-acute sequelae of SARS-CoV-2 infection (PASC) experience cognitive difficulties, compromising functional ability, quality of life, and activities of daily living, including work. However, despite this significant morbidity, there is a paucity of interventions for this disorder that have undergone evaluation within a formal trial setting. Therefore, we have developed a cognitive rehabilitation programme, specifically designed to address the cognitive symptoms of PASC, notably impaired attention and processing speed, while also accounting for other PASC symptoms (fatigue, post-exertional malaise) that may aggravate the cognitive impairment. This study protocol outlines a randomised controlled trial (RCT) designed to evaluate the effectiveness of this programme compared to standard clinical care. Methods This is a multi-centre, parallel-group, individually randomised control trial, comparing standard clinical care with and without cognitive rehabilitation. We will recruit 120 non-hospitalised adults (aged 30–60 years) from three NHS sites in England with a history of COVID-19 infection and cognitive impairment persisting more than three months after the acute infection. Participants will be randomised (1:1) to the intervention or control groups, with the latter represented as a provision of standard clinical care without cognitive rehabilitation. The cognitive rehabilitation programme consists of ten one-hour sessions, delivered weekly. Outcomes will be collected at baseline, three and six months, with participant-defined goal-attainment scores, relating to functional goals, at three months as the primary outcome measure. Secondary outcomes will be cognitive function, measures of quality of life, social functioning, mental health, fatigue, sleep, post-exertional malaise, and social and health care service use. We will also evaluate the health-economic benefits of cognitive rehabilitation in this population. Discussion Cognitive impairment in PASC is a major cause of functional disability with no effective treatment. Accordingly, we will undertake an RCT of cognitive rehabilitation, the protocol of which is published here. If this trial is successful in delivering improvements in trial outcomes, it will address a major unmet need relating to this emergent disorder, with a significant impact on affected individuals and the wider health economy. Trial registration NCT05731570.

Previous behavioural data indicate lower word‐nonword recognition accuracy in association with a high level of positive schizotypy, psychopathy, or motor impulsivity traits, each with some unique contribution, in the general population. This study aimed to examine the neural underpinnings of these associations using functional magnetic resonance imaging (fMRI) in a volunteer sample. Twenty‐two healthy English‐speaking adults completed self‐report measures of schizotypy (Oxford‐Liverpool Inventory of Feelings and Experiences [O‐LIFE]), psychopathy (Triarchic Psychopathy Measure [TriPM]), and impulsivity (Barratt Impulsiveness Scale [BIS‐11]) and underwent whole‐brain fMRI while performing a lexical decision task (LDT) featuring high and low‐frequency words, real nonwords, and pseudohomophones. Higher positive schizotypy (Unusual Experiences) was associated with lower cerebellum activity during identification of low‐frequency words (over real nonwords). Higher Boldness (fearless dominance) and Meanness (callous aggression) facets of psychopathy were associated with lower striatal and posterior cingulate activity when identifying nonwords over words. Higher Motor Impulsivity was associated with lower activity in the fusiform (bilaterally), inferior frontal (right‐sided), and temporal gyri (bilaterally) across all stimuli‐types over resting baseline. Positive schizotypy, psychopathy, and impulsivity traits influence word‐nonword recognition through distinct neurocognitive mechanisms. Positive schizotypy and psychopathy appear to influence LDT performance through brain areas that play only a supportive (cerebellum) or indirect role in reading‐related skills. The negative association between Motor Impulsivity and activations typically found for phonological processing and automatic word identification indicates a reduced bilateral integration of the meaning and sound of mental word representations, and inability to select the appropriate outputs, in impulsive individuals.

Background: Good reading skills are important for appropriate functioning in everyday life, scholastic performance, and acquiring a higher socioeconomic status. We conducted the first systematic review and meta-analysis to quantify possible deficits in specific reading skills in people with a variety of mental illnesses, including personality disorders (PDs).Methods: We performed a systematic search of multiple databases from inception until February 2020 and conducted random-effects meta-analyses.Results: The search yielded 34 studies with standardized assessments of reading skills in people with one or more mental illnesses. Of these, 19 studies provided data for the meta-analysis. Most studies (k = 27; meta-analysis,k = 17) were in people with schizophrenia and revealed large deficits in phonological processing (Hedge’sg = −0.88,p < 0.00001), comprehension (Hedge’sg = −0.96,p< 0.00001) and reading rate (Hedge’sg = −1.22,p = 0.002), relative to healthy controls; the single-word reading was less affected (Hedge’sg = −0.70,p< 0.00001). A few studies in affective disorders and nonforensic PDs suggested weaker deficits (for all, Hedge’sg< −0.60). In forensic populations with PDs, there was evidence of marked phonological processing (Hedge’sg = −0.85,p < 0.0001) and comprehension deficits (Hedge’sg = −0.95,p = 0.0003).Conclusions: People with schizophrenia, and possibly forensic PD populations, demonstrate a range of reading skills deficits. Future studies are needed to establish how these deficits directly compare to those seen in developmental or acquired dyslexia and to explore the potential of dyslexia interventions to improve reading skills in these populations.

Cognitive rehabilitation is a highly individualised, non-pharmacological intervention for people with mild cognitive impairment (MCI) and dementia, which in recent years has also been developed for various IT platforms. In this study, we aim to evaluate the effectiveness of the cognitive rehabilitation software GRADIOR in a multi-centre, single-blinded randomised controlled trial with people with MCI and mild dementia. A total of 400 people with MCI and mild dementia will be randomly allocated to one of four groups. This trial will compare the cognitive rehabilitation treatment using the GRADIOR programme with a psychosocial stimulation intervention (PSS) using the ehcoBUTLER platform, with a combined treatment consisting of GRADIOR and ehcoBUTLER, and with a group receiving treatment as usual during a period of 1 year. The outcomes of this clinical trial will be to determine any relevant changes in cognition, mood, quality of life, activities of daily living and quality of patient-carer relationship after 4 months and 1 year of intervention in a cross-sectional group comparison. Participants will be followed-up for 1 year to investigate potential long-term effects of the conducted treatments. Current Controlled Trials ISRCTN, ID: 15742788 . Registered on 12 June 2017.