Background: Bipolar disorder (BD) has been linked to substance use and cognitive declines, yet BD polygenic risk score (PRS) was associated with greater educational and occupational attainment that protect against cognitive decline. This study aimed to examine the effects of PRS-BD on executive functions and brain tissue volumes via educational and occupational attainment, alcohol use, and smoking.

Methods: The sample comprised 15,425 respondents aged 60 or above recruited from the UK Biobank between 2006 and 2010. Baseline collection included educational attainment, income, occupational complexity, alcohol frequency, and smoking history. Grey and white matter volumes were collected via magnetic resonance imaging in 2014. The participants completed the executive functions tests on Trail Making Tests and symbol digit substitution in 2021. Path analysis was conducted with 10,000 bootstrap samples in Mplus 8.8. Covariates included sex, age, neighbourhood economic deprivation, and 12 PRS principal components.

Results: PRS-BD showed significant negative total and direct effects on all three cognitive tests on trail making and symbol digit substitution. There were negative indirect effects on the tests via alcohol frequency and grey matter volume, and on trail making test – B through smoking history and grey matter volume. However, it showed positive indirect effects on all three tests via educational attainment and income.

Conclusions: This 15-year longitudinal study found significant negative effects from PRS-BD to executive functions through alcohol and smoking history, despite protective effects of education and income. Reducing alcohol consumption and avoiding smoking in those with elevated PRS-BD could protect brain health and cognition.

Authors:
Ted Chun Tat Fong, The University of Hong Kong, Hong Kong
Ryder Tsz Hong Chan, The University of Hong Kong, Hong Kong

About the Presenter(s)
Mr. Ryder Tsz Hong Chan is currently a Senior Research Assistant in the Department of Social Work and Social Administration, the University of Hong Kong. He currently investigates lifestyle factors that contribute to or mitigate cognitive decline.

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