A Blood-Based Lipid Profile Associated With Hippocampal Volume and Brain Resting-State Activation Within Obese Adults from the UK Biobank

Abstract

Objectives:

Obesity and dyslipidemia may be associated with hippocampal alterations and may increase the risk of neurodegeneration. This study studied hippocampal anatomical and functional association with a lipid profile based on high-density lipoprotein, low-density lipoprotein, and triglyceride related to dyslipidemia in obese and nonobese adults. A whole-brain analysis was also conducted to examine the effect of dyslipidemia on resting-state function across the brain.

Participants and Methods:

In total, 553 UK Biobank participants comprised three groups based on body mass index (BMI) rankings: obese adults with high BMI (O_High, n = 184, 32.7 kg/m² ≤ BMI ≤53.4 kg/m²), obese adults with a lower BMI (O_Low, n = 182, 30.3 kg/m² ≤ BMI ≤32.6 kg/m²), and nonobese controls (n = 187). Structural MRI and functional MRI data were accessed. The fractional amplitude of low-frequency fluctuations (fALFFs) maps was calculated to reflect resting-state brain activity. A lipid health factor was created using principal component analysis. Linear models tested for associations between the lipid health score and hippocampal MRI readouts.

Results:

With a higher lipid health factor corresponding to a lower dyslipidemia risk, we found a positive correlation between hippocampal volume with the lipid health factor exclusively in group O_Low (p = 0.01). We also found a positive association between the lipid health factor and hippocampal fALFF in group O_High (p = 0.02). Additional fALFF voxel-wise analysis to group O_High also implicated that the premotor cortex, amygdala, thalamus, subcallosal cortex, temporal fusiform cortex, and middle temporal gyrus brain regions are related with lipid.

Conclusion:

The study finds novel associations among circulating lipid, hippocampal structure, and hippocampal function exclusively in the obese adults.

Impact statement

This study reveals novel associations between lipid profiles and volumetric/functional estimates of the hippocampus within obese adults but not in control adults using a functional MRI approach. Further analyses revealed more brain regions showing the lipid–brain function association exclusively within highly obese adults. With a relatively large sample size and comparable demographics between groups, the research also suggests meaningful lipid–brain associations that may depend on anthropomorphic subgroups.