Relation between functional and cognitive impairments in remitted patients with bipolar disorder and suggestions for trials targeting cognition: An exploratory study

Background: Trials targeting cognition in bipolar disorder (BD) are advised to include a measure of functional capacity as key secondary or co-primary outcome to assess whether treatment efficacy on cognition translates into enhanced functional capacity. However, it is unclear which measure of functional capacity shows the strongest association with objectively-measured cognition and may thus be best suited for inclusion in cognition trials. Methods: Participants (N = 58) with BD in partial or full remission with objective cognitive impairment and healthy controls (N = 37) were assessed with mood ratings and were given a comprehensive battery of neuropsychological tests and a questionnaire assessing subjective cognitive function, respectively. They were also assessed with performance-based, interview-based and self-reported measures of functional capacity. Associations between objective and subjective cognition and measures of functional capacity were assessed with correlation analyses. For significant correlations, multiple regression analyses were conducted to assess if the associations remained significant after adjustment for clinical and demographic variables. Results: Objectively-measured cognition was directly associated with performance-based functional capacity (beta = 0.37, p < 0.01) also after adjustment for clinical and demographic variables, but not with self-reported or interview-based functional capacity (ps >= 0 .20). In contrast, subjective cognitive complaints were associated with self-reported (beta = 0.59, p < 0.01) and interview-based functional capacity (beta = 0.47, p < 0.01), but not performance-based functional capacity (ps >= 0.28). Limitations: The cross-sectional design and modest sample size. Conclusions: A performance-based measure of functional capacity seems most feasible for inclusion as a secondary outcome in cognition trials to capture improved functional capacity following treatment-related improvements in cognition.