Dissect the Heterogeneity of Longitudinal Cognitive Declines with Risk Factors and Functional Outcomes in Bipolar Disorder

Background: We characterized the heterogeneity and risk factors of cognitive decline in bipolar disorder (BD), and their magnitude of associations with subjective daily functions. Methods: Recruited BD patients (N=127) were followed for an average of 6.5 years. Baseline intelligence quotient was measured, and Brief Assessment of Cognition in Affective Disorders (BAC-A) was used to assess cognition at follow-up. We evaluated current functions with World Health Organization Disability Assessment Schedule 2.0. Clinical and sociodemographic factors were compared between BD patients with and without longitudinal cognitive decline and revealed the independent risk factors through multiple regression analysis. Correlations between specific cognitive domains and functional outcomes were examined in subgroups of BD.Results: Overall, 32.3% of BD patients showed longitudinal cognitive decline. In cognitive decline group, all cognitive domains of BAC-A were significantly worsened. Baseline independent risk factors for cognitive decline were older age, body mass index >25, and manic episode density during the disease course. After the age of 40 years, a steeper cognitive change was observed in the cognitive decline group. Housekeeping dysfunction was the most sensitive function related to diverse cognitive impairment in cognitive decline group. The correlations between cognitive domains and functional outcomes differed between patients with and without cognitive decline.Conclusions: This study characterized cognitive heterogeneity longitudinally in BD, as the foundation to facilitate future genetic and biological studies for BD subtypes. Manic episode density and overweight are important risk factors for cognitive decline; therefore, we suggested further interventions should target on relapse prevention and controlling body weight.