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Associations between obesity indices and cognitive function: Evidence from a middle-aged observational and Mendelian
Sisi Luan1, Jinyan Zhang2, Pan Luo3
1Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Diabetes, Obesity & Metabolism
|November 6, 2025
Summary
Higher body mass index (BMI), waist-hip ratio (WHR), and trunk fat mass (TFM) are linked to cognitive decline in middle-aged adults. These obesity measures show a causal relationship with reduced cognitive function, impacting memory and fluid intelligence.
Area of Science:
- Neuroscience
- Public Health
- Genetics
Background:
- Inconsistent findings exist regarding obesity's impact on cognitive decline across age groups.
- Obesity indices like BMI, WHR, and TFM are potential contributors to cognitive impairment.
Purpose of the Study:
- To investigate the associations between BMI, WHR, and TFM with cognitive function in middle-aged adults.
- To explore potential causal relationships using a Mendelian randomization (MR) approach.
Main Methods:
- Cross-sectional analysis of 72,899 UK Biobank participants using multivariable linear regression.
- Mendelian randomization analyses utilizing genome-wide association study data for BMI, WHR, and TFM as exposures and cognitive outcomes (fluid intelligence, memory, processing speed).
Main Results:
- Higher BMI and WHR were consistently associated with poorer cognitive performance, including fluid intelligence and memory.
- Increased TFM also showed adverse associations with memory performance.
- MR analyses supported a causal relationship between BMI, WHR, TFM, and cognitive decline in specific domains.
Conclusions:
- Obesity indices (BMI, WHR, TFM) are negatively associated with cognitive function in middle-aged individuals.
- Evidence suggests a causal link between these obesity measures and cognitive decline.
- Further large-scale studies are recommended for validation.
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