Validity and reliability of the COgnitive Complaints in Bipolar disorder Rating Assessment (COBRA) in Italian bipolar patients

Caterina Portaluppi1, Elena Teobaldi1, Giorgia Porceddu1,2, Camilla Garrone1, Giuseppe Maina1,2, Eduard Vieta3, Gianluca Rosso1,2

1Department of Neurosciences “Rita Levi Montalcini”, University of Turin, Italy; 2Psychiatric Unit, San Luigi Gonzaga University Hospital, Orbassano (Turin), Italy; 3Institute of Neuroscience, University of Barcelona, Hospital Clinic, IDIBAPS, CIBERSAM, Barcelona, Spain.

Summary. Background. Although bipolar disorder (BD) and cognitive impairment are straightly connected, limited tools exist to capture the patient’s perspective on cognitive decline and its impact on this disorder. The aims of the study are: 1) to assess the reliability and validity of the Italian version of a brief self-report scale (COgnitive Complaints in Bipolar disorder Rating Assessment - COBRA) among euthymic bipolar patients; 2) to investigate the relationship between the self-report scale, COBRA, the objective neurocognitive measure Screen for Cognitive Impairment in Psychiatry (SCIP), and the course of illness in BD. Methods. Western all-white sample (n=216) included 108 BD patients and 108 healthy matched controls. The psychometric properties of the COBRA (e.g., internal consistency, retest reliability, discriminative validity, factorial analysis, ROC curve and feasibility) were analyzed. A screening neuropsychological battery was used for objective cognitive assessment. Results. The Italian version of the COBRA (COBRA-I) had a high internal consistency (Cronbach’s alpha= 0.852) and retest reliability (ICC=0.848). Factor analysis validated the one-factor model, and the cut-off value was obtained with a score of 10.5. BD patients experienced greater cognitive complaints compared to control group suggesting a discriminative validity of the instrument. No significant correlation was found between COBRA and SCIP in the patients group. Higher COBRA scores were associated with BD type II, life-time hypomanic episodes and number of total episodes. Conclusions. The study proved the validity of the COBRA-I as a simple and reliable self-report instrument for screening or monitoring cognitive complaints in adult patients with BD.

Key words. Bipolar disorder, COBRA, cognitive assessment, self-report scale, validity and reliability.

Validità e affidabilità del COgnitive Complaints in Bipolar disorder Rating Assessment (COBRA) nei pazienti bipolari italiani.

Riassunto. Introduzione. Nonostante la stretta correlazione tra disturbo bipolare (DB) e deterioramento cognitivo, gli strumenti disponibili per acquisire la prospettiva del paziente riguardo al declino cognitivo e al suo impatto su questo disturbo sono limitati. Gli obiettivi dello studio sono: 1) valutare l’affidabilità e la validità della versione italiana di una breve scala auto-riferita (COgnitive Complaints in Bipolar disorder Rating Assessment - COBRA) tra pazienti bipolari eutimici; 2) analizzare la relazione tra la scala auto-riferita COBRA, la misura neurocognitiva obiettiva Screen for Cognitive Impairment in Psychiatry (SCIP) e il decorso della malattia nel DB. Metodi. Il campione, proveniente da una popolazione italiana di individui di origine caucasica (n=216), comprendeva 108 pazienti affetti da DB e 108 controlli sani appaiati per genere, età e livello d’istruzione. Sono state analizzate le proprietà psicometriche della COBRA (per es., consistenza interna, affidabilità al test-ripetizione, validità discriminativa, analisi fattoriale, curva ROC e fattibilità). Per la valutazione cognitiva obiettiva è stata utilizzata una batteria neuropsicologica di screening. Risultati. La versione italiana della COBRA (COBRA-I) ha mostrato un’elevata consistenza interna (alpha di Cronbach= 0,852) e una buona affidabilità al test-ripetizione (ICC=0,848). L’analisi fattoriale ha convalidato il modello a un fattore, con un valore di cut-off ottenuto a 10,5. I pazienti con DB hanno riportato un numero maggiore di lamentele cognitive rispetto al gruppo di controllo, suggerendo una validità discriminativa dello strumento. Non è stata trovata una correlazione significativa tra la COBRA e la SCIP nel gruppo di pazienti. Punteggi più elevati della COBRA sono risultati associati al DB di tipo II, alla presenza di episodi ipomaniacali nel corso della vita e al numero totale di episodi. Conclusioni. Lo studio ha dimostrato la validità della COBRA-I come strumento semplice e affidabile per lo screening o il monitoraggio delle lamentele cognitive nei pazienti adulti con DB.

Parole chiave. COBRA, disturbo bipolare, scala auto-riferita, validità e affidabilità, valutazione cognitiva.

Introduction

Bipolar disorder (BD) is a chronic and severe psychiatric disorder that substantially reduce psycho-social functioning1. Cognitive impairment, an invalidating key feature of BD, affects domains such as attention, memory and executive functioning, influencing work capacity, treatment adherence, self-esteem and quality of life2-5. Evidence has shown that patients with BD experience cognitive difficulties both in the acute episodes (i.e., manic, hypomanic, and depressed) and during euthymic periods6-9. Nevertheless, there is a lack of consensus about the relevance in investigating neurocognitive performance in patients with BD, as well as how to do so10. A complete neurocognitive assessment (i.e., second level assessment used for full diagnostic evaluation) is long to administer and requires substantial training to use, in addition to high costs, which may limit its use, especially in daily clinical practice. Brief instruments such as the Mini Mental State Examination (MMSE)11 or Montreal Cognitive Assessment (MoCA)12, which are routinely used in medicine to screen for dementia or mild cognitive impairment, are insufficient for assessing cognitive decline in psychiatric patients and often insensitive to subtle limitations in younger patients. A brief and reliable method for screening common cognitive impairments in psychiatry, with both objective and subjective tools designed for this purpose, would be critical for multiple reasons: 1) to determine the amount of awareness of the patient’s cognitive performance; 2) to have the patient’s cognitive performance monitored longitudinally, allowing for early intervention if cognitive impairment is suspected (with referral for indepth evaluation); 3) to look for any cognitive alterations as a result of psychopharmacological treatments; 4) to provide patients with more personalized care; 5) to have a prediction of functional capability, which is essential for judgments on long-term outcome and impairment severity. At present, certain scales evaluating subjective experiences of cognitive dysfunction in psychiatric patients exist, but they are designed generically – such as the Perceived Deficits Questionnaire-20 (PDQ-20)13 – or for schizophrenia spectrum disorders14,15 leaving BD patients unable to find their symptoms described properly. The Bipolar Disorder Program at the Hospital Clinic of Barcelona16 developed the Cognitive complaints in BD Rating Assessment (COBRA), focused on key area like memory, concentration and executive function, in order to detect the main daily cognitive complaints experienced by bipolar patients. Moreover, COBRA’s simplicity and ability to capture cognitive changes across different phases of the disorder make it practical for clinical use, outperforming more complex tools such as the Multiple Abilities Self-Report Questionnaire (MASQ)17. In 2018 the task force targeting cognition of the International Society for Bipolar Disorder (ISBD) published consensus-based recommendations on how to assess and manage cognitive impairment in BD18. The key recommendations were that mental health professionals formally screen cognition of BD patients whenever possible, by means of brief, cost-effective and easy-to-administer tools, and refer patients for extensive neuropsychological evaluation when clinically required. Specifically, the task force indicated the COBRA, still to be validated in Italian, and the Screen for Cognitive Impairment in Psychiatry (SCIP)19, already validated in Italian, as the most feasible tools for the screening of subjective and objective cognition, respectively. Both instruments are free of charge, brief, and do not require specific training for their administration. A key advantage of the COBRA is its ability to complement objective neuropsychological assessments, a feature that many other subjective tools, like the Cognitive Failures Questionnaire (CFQ)20, do not provide as effectively. There is little knowledge about the subjective perception of cognitive decline in affective disorders, and an indepth investigation of the subjective in bipolar illness is still lacking in Italy. For this reason, it is of great significance to translate the COBRA into Italian version to assess cognitive complaints reported by patients. The aims of the current study are: 1) to examine the psychometric properties of the COBRA among Italian BD patients and 2) to investigate the relationship between the COBRA, the objective cognitive measures (assessed by SCIP) and the course of illness.

Methods

Participants

A total of 216 subjects participated in the study. We included 108 patients (age 21-75 years) with DSM-5 BD type I (BD-I; n=21, 19.4%) and BD type II (BD-II; n=87, 80.6%) and meeting criteria of remission defined as a score ≤8 on the 17-Hamilton Depression Rating Scale (HAM-D)21 and on the Young Mania Rating Scale (YMRS)22 for at least three months previous to the assessment. Participants diagnosed with intellectual disability or cognitive impairment due to organic conditions were excluded. All subjects with bipolar diagnosis were outpatients enrolled in the psychiatric unit of a University Hospital, from Dec 2022 to Oct 2023. One hundred eight volunteers who did not meet criteria for any psychiatric disorder (according to the DSM-5) were included as healthy controls, matched for age, gender and years of education with patient’s group. The healthy comparison group was recruited from the general population, but we made sure that they had no first- degree relatives with BD. This study was approved by the Ethics Committee of the Hospital. After a complete verbal description of the study, all participants had written informed consent.

Assessments

Clinical and socio-demographic assessment

Socio-demographical and clinical data were collected through a semi-structured interview already used in clinical practice23. The 17-HAMD and YRMS were administered to assess depressive and manic symptoms, respectively.

Subjective cognitive measures

a) The COBRA was developed by the Bipolar Disorder Program at the Hospital Clinic of Barcelona 16 to detect the main daily cognitive complaints experienced by BD patients. The English version of COBRA24 was used to be translated into Italian version according to the British translation model. It was divided into four stages which were forward translation, back-translation, linguistic adaptation and pilot study. The first three stages were finished by cooperation among a clinical psychologist and two psychiatrists. Firstly, two independent psychiatrists translated English version into Italian and comparing the two different versions in order to reach a single one by consensus. Secondly, another psychiatrist finished back-translation then compared it with original English version to ensure conceptual equivalence. Finally, all the translators participated in the proof-reading test and the final Italian version was thus established. Subsequently, the Italian version was reviewed by a panel of experts (two senior psychiatrists and a clinical psychologist). English mother-tongue person evaluated the degree of equivalence between the English version and the Italian version. According to expert criterion, no items were modified. Next, we used the Italian version of the COBRA for a pilot study to evaluate the readability and simplicity among 20 euthymic BD inpatients in the psychiatric ward of the University Hospital. Consequently, after no modifications, the Italian version of the COBRA (COBRA-I) was ready for validation. The COBRA-I is a 16-item self-reported instrument, which allows measure subjective cognitive dysfunction including executive function, processing speed, working memory, verbal learning and memory, attention/concentration and mental tracking. All of items are rated using a 4-point scale, 0= never, 1= sometimes, 2= often, and 3= always (see English and Italian version in Appendix A). The COBRA total score is obtained when the scores of each item are added up. The higher the score, the more subjective complaints.

b) The Functional Assessment Short Test (FAST)25 is a both self-report and clinician-administered assessment scale of psychosocial dysfunction26 widely used in patients with BD. This scale includes 24 items that evaluate six functional domains (autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time). The higher the score, the greater the disability.

Objective cognitive measures

The Italian version of Screen for Cognitive Impairment in Psychiatry (SCIP-I)27 is a pencil-and-paper tool designed for rapid and objective quantification of cognitive impairment commonly observed in psychotic and affective disorders19,28-30. It has been validated in BD population, showing good sensitivity and specificity for detecting objective cognitive difficulties29,31-33. The SCIP assess five major cognitive domains that are affected in psychiatric illnesses, including immediate and delayed verbal learning, working memory, verbal fluency, and psychomotor speed. It took from 10 to 15 minutes long, depending on the participants. Cut scores offer a method to quickly identify limitations based on a SCIP total score derived from the sum of the 5 subtest scores. A SCIP total score greater than 74 is within normal limits, but scores less than 75, 65, or 55 may suggest mild, moderate, or severe limitations, respectively31. Three alternate parallel forms were developed to limit practice effects from repeat examination on five subscales selected; the first of the three forms were used in this study. The Verbal List Learning Test (VLT_I) is the first subscale and consists of three trials of a ten-item list, with total recall out of 30 as the primary outcome measure, and secondary measures that include primacy, recency, perseverations, and intrusions. The Working Memory Test (WMT) consists of eight recall trials of three-consonants, equally distributed among four conditions: no delay, or delays of 3, 9, or 18-seconds. The delay conditions are pseudo-randomly assigned to avoid successive repetition, and a three-digit number was randomly assigned from which backwards counting aloud for the delay interval provides distraction to divert resources from rehearsal. The primary outcome measure is the number of individual letters recalled out of twenty-four, regardless of order, and a secondary measure is available for scoring sequence of recall. The Verbal Fluency Test (VFT) consists of two-letters, each of which is offered in a thirty-second-generation task in which the examinee provides words that begin with the letter without producing numbers or proper nouns. The primary measure is the number of rule-consistent words produced from the two letters, with secondary measures available for perseverations, intrusions, and rule infractions. The Delayed List Learning Test (VLT_D) entails another recall trial of the verbal list after administration of the WMT and the VFT. The Psychomotor Speed Test (PST) is a novel task developed from eighteen letters of the Morse code. Six letters were assigned to each of the three forms and the corresponding Morse code dots and dashes were printed below each letter in a response key. A matrix of four rows of nine boxes is also provided, with pseudorandom assignment avoiding successive repetition of four exemplars from each of the six letters to the thirty-six boxes. The first six boxes are used for practice, prior to allowing 30 seconds to complete the remaining letters, the total of which provides the primary outcome measure.

Validity and reliability assessment

a) The internal consistency reliability and item total correlations were examined. In order to evaluate the test-retest reliability of the COBRA, the COBRA was readministered to 20 subjects (42.33 ± 7.12 years old, 12 women, 8 men) 2 weeks after the initial assessment by the same raters, and the intraclass correlation coefficient between the COBRA scores of the two assessments was calculated.

b) Concurrent validity was assessed in three ways:

• examining the relationship between COBRA results and the cognitive domain of the FAST;

• investigating the association between the COBRA and objective measures SCIP;

• studying possible correlations between the COBRA and course of the illness.

c) Discriminative validity to detect the differences between BD patients and healthy controls was analyzed using non-parametric test.

d) The optimal point for the COBRA was determined.

e) An exploratory factor analysis was performed to describe the internal structure of the COBRA.

Feasibility was described as the percentage of patients and controls who did respond to the questionnaire in its entirety.

Statistical analysis

Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS - Version 28.0., IBM Analytics) for Windows. Internal consistency was assessed by the Cronbach’s alpha. Spearman’s correlations coefficient was performed to examine the retest reliability and the possible relationship between the COBRA, FAST, SCIP and clinical course of the illness. Since data from COBRA total score followed a non-normal distribution (Kolmogorov-Smirnov test: 0.044; p<0.001), non-parametric tests were applied: the Mann-Whitney U test for continuous variables and chi-square (χ²) for categorical variables. Non-parametric tests were chosen due to the skewed distribution of the COBRA data, which violated assumptions of normality for parametric tests. The optimal point for the COBRA was determined by means of a receiver operating characteristic (ROC) curve. Exploratory factor analysis was conducted using principal axis factoring and the Quartimax rotation method was selected due to its ability to produce simple, interpretable factors with orthogonal rotation, which is suitable for identifying distinct cognitive complaint factors in this study’s data.

Trasparency and openness

Materials and analysis code for this study are available by emailing the corresponding author.

Results

A total of 216 subjects (108 with a diagnosis of BD and 108 healthy volunteers) were included in the study. The healthy comparison group matched for age, gender, and years of education with patient’s group (table 1).




Ages of the patients ranged 21-75 years (mean age= 49.82) and ages of the controls ranged 22-76 years (mean age= 48.52). Fifty-six (51.9%) patients and 61 (56.5%) of controls were women (p=0.234). Education years of the patients ranged 8-18 years (mean year= 14.52) and those of the controls ranged 8-18 years (mean year= 14.61). The 17-HAMD score and YMRS score of the patient group ranged 0-7 (mean score= 2.23) and 0-7 (mean score= 0.15); and those of the control group ranged 0-6 (mean score= 3.34) and 0-3 (mean score= 0.72). As expected, there were some significant differences in the number of people living alone and smoking (higher in the patient group) and the number of people engaging in habitual physical activity (higher in the healthy controls) based on the comparison of the two groups’ averages. Socio-demographic and clinical characteristics of the sample are shown in table 1.

Internal consistency analysis

The reliability of COBRA in terms of internal consistency was found to be good (Cronbach’s alpha= 0.862) and item-to-item correlations were between 0.305 and 0.543, suggesting that the items are sufficiently homogeneous. All items were also significantly with the COBRA total score (minus that item) with a range of 0.733-0.836. When test-retest reliability was examined, the results showed a good appropriate stability in the evaluations of patient involvement when no changes in clinical status were detected by the clinicians (ICC=0.848).

Association between COBRA and cognitive domains of FAST

A strong correlation was found between the COBRA total score and the cognitive domain of the FAST scale, indicating the concurrent validity of the instrument (rho 0.818**, p<0.001) (figure 1).




Association between subjective COBRA and neuropsychological tests of SCIP

Spearman correlations were performed to assess relationship between subjective and objective cognitive measures in both groups. In the patient group, no significant correlations were found between the COBRA score and single neuropsychological measures of the SCIP, indicating a possible lack of congruence between the objective patient’s cognitive functioning and complaints reported by, and thus the level of awareness (figure 2).




On the other hand, significant correlations were found between the COBRA total score and all single measures of the SCIP related to VLT_I (p≤0.001) and VLT_D (p≤0.001), WMT (p=0.005), VFT (p=0.005) and PST (p≤0.001) in the control group (table 2).




Association between subjective COBRA and clinical variables

The COBRA score obtained by patient group was also strongly correlated with some clinical variables of BD: duration of illness (rho=0.340, p=0.013), number of total episodes (rho=0.436, p<0.001), number of hypomanic episodes (rho=0.440, p<0.001), number of depressive episodes (rho=0.360, p=0.006), family history of psychiatric disease (rho=0.479, p<0.001) (table 3).




BD-II patients experienced more subjective complaints than subjects with BD-I (U=334, p=0.360).

Validity as a discriminative measure to detect differences between bipolar patients and healthy controls

BD patients experienced higher COBRA score (12.38 ±6.62) than healthy controls (8.42±5.20; p=0.005).

ROC curve

We analyzed the scale’s discriminative capacity between patients and controls by means of the diagnostic performance or ROC curve. The area under the curve was 0.691. 95% CI:(0.593-0.788) (figure 3).




The discriminative capacity analysis indicates that a cut-off point 10.5 obtains the best balance between sensitivity (76.8%) and specificity (57.1%).

Factorial analysis

The study of the internal structure of the COBRA after rotation (using quartimax method) determined a three-factor structure as shown in table 4.




However, as only a few items were loaded in the second and third factor and their values were closer of the first load, we considered one-dimensional structure which was responsible for 39% of the total variance.

Feasibility

Finally, the results showed a high feasibility of the COBRA since that the totality of participants answered all items of the instrument.

Discussion

The results of the present study demonstrated that the COBRA-I is a valid self-report scale to assess cognitive complaints in Italian patients with BD. The instrument exhibited satisfactory properties with high internal consistency, test-retest reliability and convergent validity as indicated by a strong correlation with the cognitive domain of the FAST scale. Furthermore, the COBRA-I results to have one-dimensional construct which means that patients tend to perceive their difficulties as a global cognitive dysfunction and allows clinicians to obtain a simple and global score (ranging from 0 to 48). Our findings are consistent with previous validations of the COBRA tool in Brazil34, China35, Japan36, and Spain24, confirming its effectiveness in assessing cognitive complaints specific to BD (table 5).




These studies highlight its reliability across cultures while noting that cultural differences can affect how cognitive difficulties are perceived and reported. One of the advantages of the COBRA over other cognitive self-reports is because it was specially designed to assess cognitive problems related to BD patients, therefore deprived of those items related to psychotic features and sometimes difficult to understand by many BD patients.

In terms of the instrument’s discriminant validity, we observed that COBRA total scores were higher in patients compared to healthy controls. Additionally, the cut-off point to discriminate subjective cognitive complaints between patients and controls was of 10.5 or above, similar to the original COBRA validation24. However, discussing the discriminative validity of a self-report instrument is challenging and the analysis requires caution, since it involves the implication of self-evaluation. Here, the degree of insight and evaluation accuracy present in objective instruments become determining criteria to be considered. Therefore, combining subjective and objective screening assessment is essential because is the way to collect relevant and complete information on the relationship between difficulties measured by the clinician and complaints reported by the patient33,37. The investigation of relationships between the COBRA self-report measure and the SCIP neuropsychological assessments adds to this. We didn’t find any associations between COBRA and the neuropsychological tests of the SCIP in the patients group. This aligns with previous research that has reported no significant correlations between subjective cognitive complaints and objective neurocognitive measures10,35,38,39. Studies assessing the relationship between subjective and objective cognitive measures have shown controversial results38,40. For instance, Faurholt-Jepsen et al.41 and Toyoshima et al.36 identified discrepancies between subjective perceptions and objective assessments, reflecting the complexities of cognitive self-reporting. Conversely, other studies, such as Lin et al.42 and Van Rheenen & Rossell43, observed a link between cognitive impairment and quality of life, suggesting that subjective and objective measures can align in specific contexts.

Recently, Bonnin et al.44 have reported that the main variable involved in the discrepancies between objective and subjective cognitive impairment are the number of depressive episodes and hospitalizations; hence, the patients with more previous depressive episodes seem to overreport cognitive complaints, whereas those with more hospitalizations (as a likely proxy of more manic episodes and less insight) are more likely to underreport those. This means that some cognitive complaints are related to biographical memories which are not commonly measured by traditional neurocognitive testing. Moreover, social cognition and insight45 may be impaired in BD, but they are not generally assessed in these patients. Specifically, impairments in social cognition, including theory of mind (ToM), can hinder BD patients’ ability to accurately evaluate their cognitive and emotional states. This may lead to biased self-reports of cognitive difficulties46,47. Therefore, future research should include social cognition assessments to enhance the understanding of cognitive complaints in BD. Probably, cognitive complaints are referred to subjective experience of general cognitive problems that are not well characterized when reported by patients (e.g., memory problems). BD patients could be unable to report the cognitive impairment accurately or not be aware of their cognitive deficits but still show significant impairment in neurocognitive testing and impact on daily functioning. These difficulties are generally reported by relatives and observed by clinician48.

Furthermore, factors related to the course of the illness may also contribute to the partial association between both objective and subjective cognitive measures. Investigating possible relationships between COBRA score and clinical characteristics suggestive of the course of bipolar illness, subjective cognitive complaints were strongly associated with higher number of total episodes and hypomanic episodes, and for psychiatric familiarity. We also found that subjects with BD-II experienced more cognitive complaints than those with BD-I subtype. BD-II is widely recognized to be associated with greater number of depressive episodes49, poorer health-related quality of life50, and more anxiety disorder comorbidity51 which may contribute to the increased cognitive complaints observed in this population52. It suggests that this subgroup of patients (e.g., BD-II patients with higher number of episodes) represents a population at risk of experiencing more cognitive complaints, which might affect psychosocial functioning.

The current study has several strengths. We used the objective screening measure SCIP, which has been demonstrated to be effective when combined with the COBRA, making both tools suitable for screening purpose33,53,54. Moreover, the group of healthy controls was matched for age, sex, and years of education with the patient group, providing a well-controlled comparison. Lastly, the enrolled BD patients were euthymic with poor residual symptoms. However, there are several limitations. Firstly, all participants were recruited from a hospital, which may lead to a sample with a more severe illness course, potentially limiting the generalizability of the findings to the wider BD population. Secondly, the homogeneity of our predominantly Western, educated, and industrialized white sample further restricts generalizability, as cultural, socio-economic, and educational factors may influence the perception and reporting of cognitive complaints. Thirdly, the study’s cross-sectional design prevented us from controlling for the influence of medication on subjective and objective cognitive measures since all participants were receiving drug therapies at the time of the study55,56. Medications like mood stabilizers, antipsychotics, and antidepressants, can affect cognitive functions in different ways, complicating the interpretation of cognitive assessments. Lithium is linked to psychomotor slowing and mild memory deficits, while second-generation antipsychotics (SGAs) and antidepressants can impair cognition to varying degrees, with polypharmacy further exacerbating these effects57-60. Lastly, the lack of analysis of mixed features in bipolar episodes represents another limitation, as this could provide a more comprehensive understanding of cognitive impairments in BD.

Given these limitations, future research should focus on several key areas. First, future research should consider stratifying participants by medication regimens and employ longitudinal designs to better understand treatment impacts. Furthermore, while we used a unidimensional COBRA, future studies could consider a multifactorial approach to better capture the diverse cognitive impairments in BD and assess the specific impacts of pharmacological treatments. The lack of analysis of mixed features in BD episodes is another gap that should be addressed in future research. Moreover, exploring the possibility of stratifying results by specific cognitive domains could offer a more detailed understanding of cognitive deficits in BD. Future studies could also examine the role of affective temperaments in potential discrepancies between subjective and objective cognitive findings, as these may influence how cognitive difficulties are perceived and reported61,62. In addition, research suggests that psychoeducational interventions may improve patients’ insight and reduce discrepancies between self-reported and clinician-administered cognitive assessment in BD63,64, an area that future studies could explore further. Lastly, given that sociodemographic factors are known to influence cognitive perception in BD65,66, future research should examine these factors more closely.

Conclusions

The COBRA-I is a brief 16-item, self-reported instrument, which allows us to investigate cognitive dysfunctions focusing on executive function, processing speed, working memory, verbal learning and memory, attention/concentration and mental tracking which are the main cognitive deficits experienced by BD patients. Subjective cognitive measures were not correlated with the objective cognitive assessment but with poor course of bipolar illness. Even though self-report scales could seem biased, we should take into consideration the patient’s perception of cognitive difficulties as valid and useful clinical information67, obtained through an instrument specifically addressed to the difficulties commonly reported by BD patients in both everyday clinical practice and investigation. At the end, those scales speak about what really matters to patients and they are easy to apply, as only patient consent and literacy are necessary.

Conflict of interests: Giuseppe Maina has been a consultant/speaker for Angelini, Boehringer, Fb Health, Innovapharma, Italfarmaco, Janssen, Otsuka, Lundbeck, and Sanofi. Gianluca Rosso has been a speaker and/or consultant from Angelini, Janssen, Lundbeck, Otsuka, Viatris. Eduard Vieta has received grants and served as consultant, advisor or CME speaker for the following entities (unrelated to the present work): AB-Biotics, Abbott, Abbvie, Adamed, Angelini, Biogen, Biohaven, Boehringer Ingelheim, Casen-Recordati, Celon, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo Smith-Kline, Idorsia, Janssen, Johnson & Johnson, Lundbeck, Newron, Novartis, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris.

The COBRA is property of Dr. Vieta’s team but it can be used for free upon permission.

The data shown have never appeared in previous publications.







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