The long-term course of cognition in bipolar disorder: A systematic review and meta-analysis of patient-control differences in test-score changes

Neuropsychological impairment represents a key aspect of bipolar disorder (BD) that is evident even in early-course patients and is a strong predictor of functional outcomes among those affected. Previous meta-analyses of longitudinal studies suggest that BD-related cognitive deficits may not progress along the course of the disorder. However, short test-retest periods were used in most primary studies and comparisons with healthy controls were limited. The aim of this review was to synthesize the findings of research reports comparing long-term neurocognitive trajectories between BD patients and healthy individuals. PubMed, PsycINFO, and Scopus databases were searched from inception through July 2021. Publications were considered for inclusion if they reported cognitive test scores of BD patients and healthy controls at two different time points, with a minimum test-retest interval of 5 years. Fifteen studies compared the long-term course of cognition in BD patients with that of healthy controls. Ten of these were included in the quantitative analysis and involved 540 BD patients and 644 healthy individuals (mean follow-up period: 8.9 years). Patient-control effect sizes (standardized mean differences) were calculated for test-score changes in 24 neuropsychological variables and combined by means of meta-analytic procedures. No significant differences were found between patients and controls regarding long-term cognitive outcomes. These findings are consistent with previous shorter-term longitudinal meta-analyses and do not provide evidence for progressive cognitive deterioration in most bipolar individuals. Future studies should address the longitudinal course of cognition in different subgroups of BD patients and its prognostic and therapeutic value.