The association between adiposity and cognitive function

By Tarun Sai LomteApr 11 2023Reviewed by Lily Ramsey, LLM

In a recent study published in the International Journal of Epidemiology, researchers assessed the associations between cognitive function and adiposity.

Study: The relationship between adiposity and cognitive function: a bidirectional Mendelian randomization study in UK Biobank. Image Credit: RobertKneschke/Shutterstock.com

Background

The prevalence of obesity and cognitive impairment is high worldwide and increases with age. Obesity in adulthood has been consistently associated with reduced cognitive function.

Since studies mainly use body mass index (BMI) to measure total adiposity, the role of adiposity location in the relationship between cognition and adiposity is uncertain.

Lower cognitive function is also associated with adiposity. As such, a bidirectional causal association might exist wherein lower cognitive function leads to increased adiposity and vice versa. 

About the study

The present study examined the causal relationship between cognition and adiposity. First, the team performed observational analyses to assess the association between phenotypic adiposity measures and cognitive function and vice versa.

Second, they repeated the same analysis within a bidirectional Mendelian randomization (MR) framework. They used genetic association estimates from the United Kingdom Biobank (UKB) participants and summary statistics of genome-wide association studies (GWASs).

Baseline adiposity measures were obtained. Weight, height, body fat percentage (BF%), waist and hip circumferences were measured, and BMI and waist-hip ratio (WHR) were computed. Participants undertook cognitive assessments at baseline.

Respondents were asked to identify correct matches from six pairs of cards after memorizing their positions, and the number of incorrect matches was recorded for visual memory (VM) assessment.

Reaction time (RT) was measured as the average time required to identify matches in the Snap game correctly.

The researchers used 76, six, 28, 28, 34, 41, and 30 single-nucleotide polymorphisms (SNPs) for BMI, BF%, WHR, favorable adiposity (FA), unfavorable adiposity (UFA), RT, and VM, respectively, that achieved genome-wide significance in respective GWASs.

Linear regression was applied to explore observational associations between adiposity and cognitive function and vice versa.

The inverse-variance weighted (IVW) method was the primary MR model (MR_IVW). Two MR sensitivity analyses, MR-Egger (MR_Egger) and MR-weighted median estimator (MR_WME), were performed.

Findings

The sample comprised 378,877 individuals, with an average age of 56.7; most subjects (53.8%) were females. Males had a higher WHR and BMI but lower BF% than females. The median number of incorrect matches was three, and the median RT was 535 milliseconds.

In adjusted observational models of adiposity to cognitive function relationship, one standard deviation (SD) increase in BF% was associated with a slower RT and better VM (fewer incorrect matches).

Likewise, higher WHR and BMI were associated with better VM and faster RT. Contrastingly, MR­_IVW­ and MR­_WME analyses showed that a higher BF% was associated with faster RT.

Estimates from MR analyses using FA and UFA instruments showed that increased adiposity was associated with a lower VM score and faster RT.

In the observational analysis of the cognition-adiposity relationship, a higher RT was associated with a lower WHR/BMI and higher BF%. A higher VM score was associated with a lower WHR, BMI, and BF%.

MR estimates generally indicated that a higher RT was associated with a lower BMI and BF%. The MR_IVW, MR_WME, and MR_Egger analyses were directionally consistent with findings from the observational analysis between RT and BMI.

However, RT-WHR and RT-BF% associations were directionally inconsistent with observational findings. The three MR analyses for the effects of VM on BMI, BF%, and WHR were directionally consistent with observational results.

A one-unit higher VM score, i.e., worse VM, was associated with a 3.57% and 1.32% lower relative BMI and absolute BF%, respectively.

In sensitivity analyses, when SNPs associated with confounders were excluded, the direction of the adiposity to cognition association changed.

In the opposite direction, some associations, including VM to BMI or BF%, were consistent with the primary MR analysis, whereas the RT to BF% association was not.

Conclusions

In summary, the researchers investigated the causal associations between adiposity and cognition in the UKB and noted vital differences in the direction of associations.

They demonstrated that the effect of adiposity on cognition was unlikely causal. Further, there was limited evidence to suggest a causal link in the other direction between RT and adiposity.

Nonetheless, the findings corroborate the evidence for the causal association between poor VM and lower adiposity.