Date of Award

January 2025

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Hilary P. Blumberg

Abstract

The presentation of bipolar disorder (BD) seems to change over the course of a lifetime. In older adults, BD seems to pose novel challenges including decreased cognitive functioning, psychiatric and medical comorbidities, increased susceptibility to medication side effects, and possibly even a shift toward more depressive symptoms. Despite these clinical findings, research into older adults with BD has lagged behind that of adolescents and young adults. As the global population ages, so too do individuals with BD. In fact, it is predicted that by 2030, 50% of patients with BD will be over the age of 60. This emphasizes why it is so important to gain a deeper understanding of how BD in older adulthood differs from its clinical presentation in adolescence and young adulthood. Similarly, while research has found extensive evidence to suggest the presence of structural abnormalities in the prefrontal cortices (PFC) of adolescents and young adults with BD, there has been insufficient exploration into the neuroanatomy of older adults with BD. The goal of this study is to explore the cortical thickness of the PFC in middle and older adults with BD (MOABD) compared to that of similarly aged healthy controls (HC). Parcellated PFC cortical thickness was generated from structural magnetic resonance imaging (MRI) data using Enhancing Neuro Imaging Genetics through Meta Analysis (ENIGMA) pipelines for MOABD (n=308) and HC (n=287) ages 40-70y from six international sites of the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) research consortium. Regional ventral PFC (VPFC) and dorsal PFC (DPFC) thickness between MOABD and HC groups were compared with analysis-of-covariance models covarying for site, age, and sex. Additionally, main and group interactive effects of age were explored. Within the MOABD cohort, cortical associations with clinical variables such as BD subtype, history of psychotic features, lifetime comorbidity of substance use disorder, and current medications were also explored. Cortical thickness was significantly decreased in MOABD in the VPFC as well as the DPFC (psFDR<.001). A main effect of age was observed in both the VPFC and the DPFC (psFDR<.001). However, no significant interactions between age and diagnosis were observed. Additionally, MOABD who were taking lithium were found to have significantly greater cortical thickness in DPFC regions (psFDR<.001) compared to MOABD not taking lithium. The consistency of some results with those in adolescents and younger adults with BD, such as those in VPFC, suggest that a portion of the cortical thickness decreases in BD may be neurodevelopmental and may persist into older age. This study’s findings support the theory that DPFC abnormalities may emerge later in life for individuals with BD. Medication findings concur with other research indicating that lithium may exert neuroprotective effects. However, longitudinal studies are needed to confirm any potential aging- and treatment-related changes.

Comments

This is an Open Access Thesis.

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