Cognitive Decline and Illness Progression in Bipolar Disorder

Bipolar disorder (BD) is a chronic and heterogeneous condition associated with global and specific cognitive deficits, including but not limited to impaired executive function, memory, and processing speed. As cognitive impairment represents a therapeutic target, this systematic review aims to synthesize available evidence investigating the association between clinical markers of illness progression and cognitive decline in adults with BD.

A systematic search was conducted in PubMed, OVID (PsycINFO), and Scopus from inception to September 27, 2025. Eligible studies included adults (≥ 18 years) with BD (I, II, or mixed) that reported a direct comparison between subgroups of illness progression markers (illness duration and/or number of mood episodes). The primary outcome was cognitive function assessed by validated neuropsychological tests. Eligible study designs were cross-sectional, longitudinal, case-control, cohort, or baseline clinical trial data.

Available evidence from cross-sectional studies suggest that a higher number of mood episodes or longer illness duration was associated with decreased cognitive function, particularly in domains of executive function and verbal/visual memory. In contrast, several longitudinal studies reported no significant change in cognitive outcomes over time in persons with BD relative to healthy controls.

Findings on the influence of illness progression markers on cognitive decline in BD is mixed. Future research should prioritize large-scale longitudinal designs and integrate biomarker and neuroimaging methods to investigate underlying mechanisms that may contribute to cognitive worsening in individuals with BD.