Depression reduces cognitive function partly through effects on BMI and hypertension: a large observational study and...

Area of Science:

• Neuroscience
• Public Health
• Genetics

Background:

• The link between depression and cognitive impairment is established, but the causal relationship and underlying mechanisms remain unclear.
• Understanding these connections is crucial for developing effective interventions.

Purpose of the Study:

• To investigate the causal relationship between depression and cognitive function.
• To identify mediating factors, such as obesity and hypertension, in this association.

Main Methods:

• Utilized data from the National Health and Nutrition Examination Survey (NHANES).
• Employed weighted multivariable-adjusted linear regression for observational analysis.
• Applied Mendelian randomization (MR) analysis to infer causality and mediation.

Main Results:

• Observational data confirmed an independent association between depression and cognitive function.
• MR analysis revealed a causal link between genetically predicted depression and cognitive function (OR 0.33, P=0.012).
• Depression was found to causally increase risks for obesity (OR 1.91, P=2.53×10⁻³), elevated blood pressure (OR 2.34, P=3.62×10⁻³), BMI (OR 0.84, P=1.06×10⁻⁶), and hypertension (OR 0.95, P=4.00×10⁻³).
• Obesity (via BMI) and hypertension mediated 9.9% and 3.6% of the effect of depression on cognitive function, respectively.

Conclusions:

• Depression causally contributes to cognitive impairment, partly through mediating effects of obesity and hypertension.
• Timely management of depression, alongside interventions targeting weight and blood pressure, is vital for preventing cognitive decline.