The association between sleep spindles and cognitive performance in euthymic bipolar disorder

Intro: Many people with bipolar disorder (BD) experience persistent cognitive deficits. Sleep spindles have been linked to cognitive ability in healthy populations and psychotic disorders. While there is preliminary evidence for altered spindle activity in BD, research directly examining the association between sleep spindle parameters and cognitive performance in this population is lacking. Therefore, our primary objective was to examine the association between fast spindle density and episodic memory performance in euthymic individuals with BD, hypothesising a positive relationship. As exploratory analyses, we looked at associations between fast and slow spindle density and subjective sleep quality with other cognitive domains. We also conducted a sensitivity analysis, separating all analyses by lithium intake. Methods: Thirty-four euthymic participants with BD underwent comprehensive cognitive assessments and were assessed for three consecutive nights using mobile sleep-EEG headbands. Sleep spindles were detected using validated, adapted, fully automated algorithms, subdivided into slow (≤13 Hz) and fast (>13 Hz) spindles, and characterised by density. Results: Contrary to our hypothesis, fast spindle density was not associated with episodic memory performance (r=-.004, p=.491, 95% CI [-.353, .499]) but did show a significant positive association with working memory in exploratory analyses (r=.423, p=.014, 95% CI [-.167, .722]). When removing participants taking lithium from analyses, several positive significant associations emerged between fast spindle density and cognitive performance.Conclusions: These findings suggest domain-specific relationships between sleep spindle activity and cognition in BD, with fast spindles potentially being associated with working memory. Preliminary evidence for lithium-related modulation highlights the importance of considering pharmacological factors. However, the analyses were underpowered, and large-scale studies are needed to deepen our understanding of sleep spindle-cognition relationships in BD.Keywords: bipolar disorder; cognition; episodic memory; working memory; sleep spindles; sleep-EEG; lithium