Associations between obesity indices and cognitive function: Evidence from a middle‐aged observational and Mendelian randomisation study
Authors' conclusion
This study demonstrates a negative association between BMI, WHR, TFM and cognitive function in middle-aged populations. Moreover, BMI, WHR and TFM appear to have a causal relationship with specific domain cognitive decline. Further multicentre, multiregional and large-scale studies are required to validate these findings.
Study context
- Population
- Middle-aged UK Biobank participants; Mendelian randomisation (MR) using European-ancestry GWAS of cognitive outcomesUK Biobank
- Participants
- 72,899 participants
- Exposure
- Highest vs lowest tertiles of obesity indices
- Outcome
- Cognitive function by obesity index tertile (fully adjusted)
Methodological detailsmultivariable linear regression, inverse-variance weighted MR, sensitivity analyses for pleiotropy, Benjamini-Hochberg correction
- Multivariable linear regression
- Inverse-variance weighted MR
- Sensitivity analyses for pleiotropy
- Benjamini-Hochberg correction
Main finding
As reported in the abstract
- T3
- β (body mass index (BMI), fluid intelligence score (FIS)) −0.024 (95% CI −0.042 to −0.006); p_BH = 0.032
- T3
- β (BMI, memory) −0.111 (95% CI −0.130 to −0.092); p_BH <0.001
- T3
- β (waist-hip ratio (WHR), FIS) −0.072 (95% CI −0.096 to −0.048); p_BH <0.001
- T3
- β (WHR, memory) −0.116 (95% CI −0.141 to −0.090); p_BH <0.001
- T3
- β (WHR, processing) −0.091 (95% CI −0.115 to −0.068); p_BH <0.001
- T3
- β (trunk fat mass (TFM), memory) −0.075 (95% CI −0.094 to −0.056); p_BH <0.001
Observational data: associations, not effects.
Further findings
MR: genetically predicted BMI, WHR and FIS
- Associations between BMI, WHR and FIS remained significant after Benjamini-Hochberg correction, corroborated by MR robust adjusted profile score and all sensitivity analyses
- p_MR_BH <0.05
Original publication
Associations between obesity indices and cognitive function: Evidence from a middle‐aged observational and Mendelian randomisation study. Diabetes Obes Metab. Published 5 November 2025. doi:10.
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