Background:Patients with bipolar disorder (BD) suffer from cognitive deficits across several domains. The association between cognitive performance and psychosocial functioning has led to the emergence of cognition as a treatment target.Objective: This study reviews the existing literature on cognitive enhancement interventions for people with BD, focusing on different treatment approaches and methodological quality. Methods:We conducted a systematic search following the PRISMA guidelines. Sample characteristics and main outcomes for each study and treatment characteristics for each approach were extracted. Study quality was assessed using the Clinical Trials Assessment Measure (CTAM) and Cochrane Collaboration's Risk of Bias tool by independent raters.Results: Eleven articles reporting data from seven original studies were identified encompassing 471 participants. Two treatment approaches were identified, cognitive and functional remediation. For controlled studies, methodological quality was modest (average CTAM score = 60.3), while the overall risk of bias was considered moderate. Beneficial effects on cognitive or functional outcomes were reported in the majority of studies (91%), but these findings were isolated and not replicated across studies. Key methodological limitations included small sample sizes, poor description of randomization process, high attrition rates, and participant exclusion from the analysis. Conclusions:Findings are promising but preliminary. Quality studies were few and mostly underpowered. Heterogeneity in sample characteristics, outcome measures, and treatment approaches further limit the ability to generalize findings. Adequately powered trials are required to replicate initial findings, while moderators of treatment response and mechanisms of transfer need to be explored. K E Y W O R D S bipolar disorder, cognition, cognitive remediation, functional remediation, functioning, methodological quality | 217 TSAPEKOS ET Al

BackgroundThere is evidence that cognitive remediation (CR) is moderately effective in improving cognitive and functional difficulties in people with schizophrenia. However, there is still a limited understanding of what influence different treatment responses.AimTo identify moderators influencing CR response in people with schizophrenia.MethodsThis systematic review follows PRISMA guidelines. Searches were conducted up to January 2019 on PubMed and PsychInfo to identify randomized controlled trials of CR reporting analyses of moderators of treatment response. All papers were assessed for methodological quality and information on sample size, intervention and control condition, moderators, outcomes, effect of moderator on outcomes and demographic characteristics from each study was extracted and critically summarised.ResultsThirty-six studies were included, considering 2737 participants. Study participants consisted on average of people in their late-thirties, mostly men, with over 10 years of illness. The review identified moderators that could be grouped into five categories: demographics, biological, cognitive and functional, psychological, and illness-related characteristics. The assessment of methodological quality showed that many studies had a high risk of bias.ConclusionsThere was no high-quality replicated evidence which identifies reliable moderators of CR response. Many moderators were not replicated or presented in single, underpowered studies. Studies also investigated moderators independently despite their potential to overlap (e.g. age and education). Future research should concentrate on evaluating, with sound studies, the role moderators may play in affecting CR treatment response. This information can inform who will benefit most from the therapy and help to improve the benefits of CR.

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BackgroundCognitive deficits are common in people with schizophrenia and have a negative impact on functioning. Cognitive Remediation (CR) is an effective approach to reduce the burden of cognitive difficulties however there are individual differences in therapy response. Previous research suggests that participants age may be a significant moderator of therapy efficacy but results are inconclusive. This study attempts to fill this gap by exploring how age may influence CR outcomes.MethodsData from ten trials from the NIMH Database of Cognitive Training and Remediation Studies (DoCTRS) were used. We considered the following therapy outcomes: Executive function as assessed by the Trail making test part B (TMTB), the Wisconsin Card Sorting Test (WCST) and Verbal fluency (FAS) scores. Working memory was assessed with the Letter-Number Span (LNS) and the Digit span. Symptoms were evaluated with the Positive, Negative and General scores from the Positive and Negative Syndrome Scale (PANSS). Functioning was assessed using the Heinrichs-Carpenter quality of life (HCQOL) scale. To evaluate the effect of age on outcomes we classified participants into under 40 and over 40 years old. We compared outcomes across age groups using mixed linear models.ResultsWe considered data from 711 people with schizophrenia (407 received CR and 304 the control condition). For the under 40 group the average age was 29.26 (SD 6.83) while the average yeas spent in education was 12.11 (2.61). The over 40 group had a mean age of 40.09 (SD 6.09) and 12.11 (2.54) years of education.We found a significant interaction between age and working memory and functioning improvement for the over 40 group. The younger group showed a larger effect of CR in term of general symptoms reduction. We did not find an effect of age on executive function, positive and negative symptom.DiscussionThe results indicate that CR may benefit people with schizophrenia in different way depending on their age. Age may represent a large number of complex factors and more work is needed in this area to better understand how individual characteristics and illness history may influence CR response. Work in this sense will help to reduce CR response heterogeneity and improve therapy personalisation.