Objectives
To aid the development of treatment for cognitive impairment in bipolar disorder, the International Society for Bipolar Disorders (ISBD) convened a task force to create a consensus‐based ...guidance paper for the methodology and design of cognition trials in bipolar disorder.
Methods
The task force was launched in September 2016, consisting of 18 international experts from nine countries. A series of methodological issues were identified based on literature review and expert opinion. The issues were discussed and expanded upon in an initial face‐to‐face meeting, telephone conference call and email exchanges. Based upon these exchanges, recommendations were achieved.
Results
Key methodological challenges are: lack of consensus on how to screen for entry into cognitive treatment trials, define cognitive impairment, track efficacy, assess functional implications, and manage mood symptoms and concomitant medication. Task force recommendations are to: (i) enrich trials with objectively measured cognitively impaired patients; (ii) generally select a broad cognitive composite score as the primary outcome and a functional measure as a key secondary outcome; and (iii) include remitted or partly remitted patients. It is strongly encouraged that trials exclude patients with current substance or alcohol use disorders, neurological disease or unstable medical illness, and keep non‐study medications stable. Additional methodological considerations include neuroimaging assessments, targeting of treatments to illness stage and using a multimodal approach.
Conclusions
This ISBD task force guidance paper provides the first consensus‐based recommendations for cognition trials in bipolar disorder. Adherence to these recommendations will likely improve the sensitivity in detecting treatment efficacy in future trials and increase comparability between studies.
Objectives
Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) ...Targeting Cognition Task Force aimed to develop consensus‐based clinical recommendations on whether, when and how to assess and address cognitive impairment.
Methods
The task force, consisting of 19 international experts from nine countries, discussed the challenges and recommendations in a face‐to‐face meeting, telephone conference call and email exchanges. Consensus‐based recommendations were achieved through these exchanges with no need for formal consensus methods.
Results
The identified questions were: (I) Should cognitive screening assessments be routinely conducted in clinical settings? (II) What are the most feasible screening tools? (III) What are the implications if cognitive impairment is detected? (IV) What are the treatment perspectives? Key recommendations are that clinicians: (I) formally screen cognition in partially or fully remitted patients whenever possible, (II) use brief, easy‐to‐administer tools such as the Screen for Cognitive Impairment in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and (III) evaluate the impact of medication and comorbidity, refer patients for comprehensive neuropsychological evaluation when clinically indicated, and encourage patients to build cognitive reserve. Regarding question (IV), there is limited evidence for current evidence‐based treatments but intense research efforts are underway to identify new pharmacological and/or psychological cognition treatments.
Conclusions
This task force paper provides the first consensus‐based recommendations for clinicians on whether, when, and how to assess and address cognition, which may aid patients’ functional recovery and improve their quality of life.
Cognitive impairment is an emerging treatment target in patients with bipolar disorder (BD) but so far, no evidence-based treatment options are available. Recent studies indicate promising effects of ...Cognitive Remediation (CR) interventions, but it is unclear who responds most to these interventions. This report aimed to investigate whether pre-treatment dorsal prefrontal cortex (dPFC) thickness predicts improvement of executive function in response to Action-Based Cognitive Remediation (ABCR) in patients with BD. Complete baseline magnetic resonance imaging (MRI) data were available from 45 partially or fully remitted patients with BD from our randomized controlled ABCR trial (ABCR: n = 25, control group: n = 20). We performed cortical reconstruction and volumetric segmentation using FreeSurfer. Multiple linear regression analysis was conducted to assess the influence of dPFC thickness on ABCR-related executive function improvement, reflected by change in the One Touch Stocking of Cambridge performance from baseline to post-treatment. We also conducted whole brain vertex wise analysis for exploratory purposes. Groups were well-matched for demographic and clinical variables. Less pre-treatment dPFC thickness was associated with greater effect of ABCR on executive function (p = 0.02). Further, whole-brain vertex analysis revealed an association between smaller pre-treatment superior temporal gyrus volume and greater ABCR-related executive function improvement. The observed associations suggest that structural abnormalities in dPFC and superior temporal gyrus are key neurocircuitry treatment targets for CR interventions that target impaired executive function in BD.
•Most patients show cognitive impairment months after hospitalization with COVID-19.•Cognitive impairments correlate with subjective cognitive problems and quality of life.•Cognitive impairments ...scale with pulmonary dysfunction and d-dimer during illness.
The ongoing Coronavirus Disease 2019 (COVID-19) pandemic has affected more than 100 million people and clinics are being established for diagnosing and treating lingering symptoms, so called long-COVID. A key concern are neurological and long-term cognitive complications. At the same time, the prevalence and nature of the cognitive sequalae of COVID-19 are unclear. The present study aimed to investigate the frequency, pattern and severity of cognitive impairments 3–4 months after COVID-19 hospital discharge, their relation to subjective cognitive complaints, quality of life and illness variables. We recruited patients at their follow-up visit at the respiratory outpatient clinic, Copenhagen University Hospital, Bispebjerg, approximately four months after hospitalisation with COVID-19. Patients underwent pulmonary, functional and cognitive assessments. Twenty-nine patients were included. The percentage of patients with clinically significant cognitive impairment ranged from 59% to 65% depending on the applied cut-off for clinical relevance of cognitive impairment, with verbal learning and executive functions being most affected. Objective cognitive impairment scaled with subjective cognitive complaints, lower work function and poorer quality of life. Cognitive impairments were associated with d-dimer levels during acute illness and residual pulmonary dysfunction. In conclusion, these findings provide new evidence for frequent cognitive sequelae of COVID-19 and indicate an association with the severity of the lung affection and potentially restricted cerebral oxygen delivery. Further, the associations with quality of life and functioning call for systematic cognitive screening of patients after recovery from severe COVID-19 illness and implementation of targeted treatments for patients with persistent cognitive impairments.
Cognitive impairment is a core feature of schizophrenia (SZ) and bipolar disorder (BD). A neurocognitive profile characterized by widespread cognitive deficits across multiple domains in the context ...of substantial intellectual impairment, which appears to antedate illness onset, is a replicated finding in SZ. There is no specific neuropsychological signature that can facilitate the diagnostic differentiation of SZ and BD, notwithstanding, neuropsychological deficits appear more severe in SZ. The literature in this field has provided contradictory results due to methodological differences across studies. Meta-analytic techniques may offer an opportunity to synthesize findings and to control for potential sources of heterogeneity. Here, we performed a systematic review of meta-analyses of neuropsychological findings in SZ and BD. While there is no conclusive evidence for progressive cognitive deterioration in either SZ or BD, some findings point to more severe cognitive deficits in patients with early illness onset across both disorders. A compromised pattern of cognitive functioning in individuals at familiar and/or clinical risk to psychosis as well as in first-degree relatives of BD patients suggests that early neurodevelopmental factors may play a role in the emergence of cognitive deficits in both disorders. Premorbid intellectual impairment in SZ and at least in a subgroup of patients with BD may be related to a shared genetically determined influence on neurodevelopment.
•Cognitive impairments were seen after 1 year in half of people hospitalised with COVID-19.•Cognitive sequelae were stable over time from 3 months to 1 year after hospitalisation.•Cognitive ...impairments impeded work functioning and quality of life.•Early cognitive impairments were related to subsequent depressive symptoms after 1 year.•Screening for and addressing cognitive impairments after severe COVID-19 may be important.
The ongoing Coronavirus Disease (COVID-19) pandemic has so far affected more than 500 million people. Lingering fatigue and cognitive difficulties are key concerns because they impede productivity and quality of life. However, the prevalence and duration of neurocognitive sequelae and association with functional outcomes after COVID-19 are unclear. This longitudinal study explored the frequency, severity and pattern of cognitive impairment and functional implications 1 year after hospitalisation with COVID-19 and its trajectory from 3 months after hospitalisation. Patients who had been hospitalised with COVID-19 from our previously published 3-months study at the Copenhagen University Hospital were re-invited for a 1-year follow-up assessment of cognitive function, functioning and depression symptoms. Twenty-five of the 29 previously assessed patients (86%) were re-assessed after 1 year (11±2 months). Clinically significant cognitive impairments were identified in 48-56 % of patients depending on the cut-off, with verbal learning and executive function being most severely affected. This was comparable to the frequency of impairments observed after 3 months. Objectively measured cognitive impairments scaled with subjective cognitive difficulties, reduced work capacity and poorer quality of life. Further, cognitive impairments after 3 months were associated with the severity of subsequent depressive symptoms after 1 year. In conclusion, the stable cognitive impairments in approximately half of patients hospitalized with COVID-19 and negative implications for work functioning, quality of life and mood symptoms underline the importance of screening for and addressing cognitive sequelae after severe COVID-19.
Objectives
We aim to characterize the cognitive performance in euthymic older adults with bipolar disorder (OABD) through a comprehensive neuropsychological assessment to obtain a detailed ...neuropsychological profile.
Methods
We conducted a systematic search in MEDLINE/Pubmed, Cochrane, and PsycInfo databases. Original studies assessing cognitive function in OABD (age ≥50 years ) containing, at a minimum, the domains of attention/processing speed, memory, and executive functions were included. A random‐effects meta‐analysis was conducted to summarize differences between patients and matched controls in each cognitive domain. We also conducted meta‐regressions to estimate the impact of clinical and socio‐demographic variables on these differences.
Results
Eight articles, providing data for 328 euthymic OABD patients and 302 healthy controls, were included in the meta‐analysis. OABD showed worse performance in comparison with healthy controls, with large significant effect sizes (Hedge's g from −0.77 to −0.89; p < 0.001) in verbal learning and verbal and visual delayed memory. They also displayed statistically significant deficits, with moderate effect size, in processing speed, working memory, immediate memory, cognitive flexibility, verbal fluency, psychomotor function, executive functions, attention, inhibition, and recognition (Hedge's g from −0.52 to −0.76; p < 0.001), but not in language and visuoconstruction domains. None of the examined variables were associated with these deficits.
Conclusions
Cognitive dysfunction is present in OABD, with important deficits in almost all cognitive domains, especially in the memory domain. Our results highlight the importance of including a routine complete neuropsychological assessment in OABD and also considering therapeutic strategies in OABD.
Bipolar disorder (BD) is commonly associated with cognitive impairments, that directly contribute to patients' functional disability. However, there is no effective treatment targeting cognition in ...BD. A key reason for the lack of pro-cognitive interventions is the limited insight into the brain correlates of cognitive impairments in these patients. This is the first study investigating the resting-state neural underpinnings of cognitive impairments in different neurocognitive subgroups of patients with BD.
Patients with BD in full or partial remission and healthy controls (final sample of n = 144 and n = 50, respectively) underwent neuropsychological assessment and resting-state functional magnetic resonance imaging. We classified the patients into cognitively impaired (n = 83) and cognitively normal (n = 61) subgroups using hierarchical cluster analysis of the four cognitive domains. We used independent component analysis (ICA) to investigate the differences between the neurocognitive subgroups and healthy controls in resting-state functional connectivity (rsFC) in the default mode network (DMN), executive central network (ECN), and frontoparietal network (FPN).
Cognitively impaired patients displayed greater positive rsFC within the DMN and less negative rsFC within the ECN than healthy controls. Across cognitively impaired patients, lower positive connectivity within DMN and lower negative rsFC within ECN correlated with worse global cognitive performance.
Cognitive impairments in BD seem to be associated with a hyper-connectivity within the DMN, which may explain the failure to suppress task-irrelevant DMN activity during the cognitive performance, and blunted anticorrelation in the ECN. Thus, aberrant connectivity within the DMN and ECN may serve as brain targets for pro-cognitive interventions.
Background:
Mood disorders are often associated with persistent cognitive impairments. However, pro-cognitive treatments are essentially lacking. This is partially because of poor insight into the ...neurocircuitry abnormalities underlying these deficits and their change with illness progression.
Aims:
This functional magnetic resonance imaging (fMRI) study investigates the neuronal underpinnings of cognitive impairments and neuronal change after mood episodes in remitted patients with bipolar disorder (BD) using a hippocampus-based picture encoding paradigm.
Methods:
Remitted patients with BD (n=153) and healthy controls (n=52) were assessed with neuropsychological tests and underwent fMRI while performing a strategic picture encoding task. A subgroup of patients (n=43) were rescanned after 16 months. We conducted data-driven hierarchical cluster analysis of patients’ neuropsychological data and compared encoding-related neuronal activity between the resulting neurocognitive subgroups. For patients with follow-up data, effects of mood episodes were assessed by comparing encoding-related neuronal activity change in BD patients with and without episode(s).
Results:
Two neurocognitive subgroups were revealed: 91 patients displayed cognitive impairments while 62 patients were cognitively normal. No neuronal activity differences were observed between neurocognitive subgroups within the dorsal cognitive control network or hippocampus. However, exploratory whole-brain analysis revealed lower activity within a small region of middle temporal gyrus in impaired patients, which significantly correlated with poorer neuropsychological performance. No changes were observed in encoding-related neuronal activity or picture recall accuracy with the occurrence of mood episode(s) during the follow-up period.
Conclusion:
Memory encoding fMRI paradigms may not capture the neuronal underpinnings of cognitive impairment or effects of mood episodes.
•Residual anxiety in bipolar disorder impedes treatment effect and prognosis•10 trials investigated treatments targeting anxiety in remitted bipolar disorder•There is limited evidence for efficacy of ...treatments targeting anxiety•Common methodological challenges impede the success of treatment trials•These challenges must be addressed to aid the success of future trials
Anxiety symptoms are prevalent in bipolar disorder (BD) even during periods of remission and impede treatment efficacy, prognosis and functional capacity. This highlights a pressing clinical need to identify novel effective anxiety treatments. This systematic review aimed to evaluate the evidence within the field.
Following PRISMA guidelines, we conducted a systematic search on PubMed, PsycInfo, EMBASE and Cochrane Library for randomised controlled trials (RCTs) targeting anxiety in remitted BD patients.
We identified 10 RCTs investigating the effects of psychological or pharmacological treatments on anxiety in remitted BD patients. Two studies of transdiagnostic personalised cognitive behavioural therapy (CBT) found a treatment-related reduction in anxiety. This evidence was preliminary given small sample size and use of self-report measures in a single-blind trial design, respectively. The remaining six psychological intervention trials provided more preliminary evidence due to several methodological challenges. The two pharmacological studies found anxiolytic effects of add-on olanzapine or methylene blue to lithium treatment, respectively. Nevertheless, this evidence should be interpreted with caution given high drop-out rates and substantial side-effects that may have impeded blinding.
We did not conduct a quantitative meta-analysis.
There is preliminary evidence for beneficial effects of modified CBT and add-on pharmacotherapy on residual anxiety in BD. Future trials should pre-screen participants for anxiety, define one clinician-rated anxiety measurement as a primary outcome, and employ intention-to-treat analysis to assess treatment effect. This will advance treatment development and enable personalised approaches to address residual anxiety in BD, which has great clinical relevance.
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