Higher Blood Pressure Partially Links Greater Adiposity to Reduced Brain White Matter Integrity

Background: Adiposity and elevated blood pressure (BP) are associated with brain structure abnormalities, but whether these effects are independent is unknown. We tested whether associations between adiposity and white matter integrity were explained by elevated BP.

Methods: A sample of 209 middle-aged adults underwent diffusion tensor imaging to quantify indirect metrics of white matter structural integrity. These included putative markers of global white matter integrity (fractional anisotropy (FA)), axonal integrity (axial diffusivity), and myelin integrity (radial diffusivity). Participants were either normotensive or prehypertensive.

Results: After adjusting for age and sex, regression analyses showed that waist circumference was associated with FA (β = -0.15, P < 0.05) and axial diffusivity (β = -0.24, P < 0.001), and mean arterial pressure (MAP) was associated with FA (β = -0.21, P < 0.05). Direct and indirect effect analyses showed that waist circumference was indirectly associated with whole brain FA through MAP (β = -0.06), and directly related to whole brain axial diffusivity, independent of MAP (β = -0.24). Examination of specific white matter tracts yielded similar results; waist circumference was indirectly related to FA through MAP and radial diffusivity, and directly related to axial diffusivity, independent of MAP. Supplemental analyses using body mass index, systolic BP, and diastolic BP also yielded similar results.

Conclusion: These findings suggest at least 2 mechanisms explain the adiposity and white matter association: one pathway through elevated BP impacting global white matter integrity and reducing integrity of the myelin sheath, and at least one other adiposity-specific pathway decreasing axonal integrity.