Causal relationship between feelings and cognitive decline: An univariable and multivariable Mendelian randomization...

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• The impact of depression on cognitive function is established, but the relationship between general feelings and cognition is less understood.
• Limited research exists on how various emotional states influence cognitive abilities.

Purpose of the Study:

• To investigate the potential causal associations between different types of feelings and cognitive functions using a two-sample Mendelian randomization (MR) approach.
• To explore the impact of specific feelings, such as sensitivity/hurt feelings and worrier/anxious feelings, on cognitive performance.

Main Methods:

• Utilized genome-wide association study (GWAS) data for multiple feelings and cognitive functions (intelligence) in a European population.
• Employed univariable (UVMR) and multivariable (MVMR) Mendelian randomization analyses, including inverse variance weighting (IVW), weighted median, and MR-Egger methods.
• Conducted sensitivity analyses, heterogeneity assessments (MR-PRESSO, Cochran's Q), and pleiotropy tests (MR-Egger regression) to ensure result validity.

Main Results:

• UVMR indicated a potential negative causal effect of sensitivity/hurt feelings on cognition (OR=0.63).
• MVMR confirmed a direct adverse causal effect of sensitivity/hurt feelings on cognition (OR_MVMR=0.39).
• Fed-up feelings showed a potential link to cognitive decline in UVMR, but this was not significant in MVMR. Worrier/anxious feelings exhibited pleiotropy, making their effect inconclusive. No significant associations were found for guilty, nervous, miserable, or lonely feelings.

Conclusions:

• Sensitivity/hurt feelings are associated with cognitive decline, highlighting their potential adverse impact on cognitive function.
• The relationship between worrier/anxious feelings and cognition remains inconclusive due to methodological challenges like pleiotropy.
• No significant direct associations were established between happiness, guilty feelings, nervous feelings, miserableness, or loneliness/isolation and cognitive function.