The role of vascular risk factors in white matter tract microstructure: a multi-cohort study in older adults
Published in Alzheimer's & Dementia, 2026
Recommended citation: LeFevre, J. D., Vyas, Y., Sathe, A., Shashikumar, N., Pechman, K. R., Yang, Y., Durant, A., Kanakaraj, P., Kim, M. E., Gao, C., Newlin, N. R., Ramadass, K., Khairi, N. M., Li, Z., Yao, T., Risacher, S. L., Zhang, P., Schilling, K. G., Lee, A. J., Brickman, A. M., Mayeux, R., Mez, J., Kukull, W., Biber, S. A., Landman, B. A., Bendlin, B. B., Johnson, S. C., Schneider, J., Barnes, L. L., Bennett, D. A., Saykin, A. J., Cuccaro, M. L., Hohman, T. J., Jefferson, A. L. and Archer, D. B., for ADNI, ADSP and ADSP-PHC (2026). "The role of vascular risk factors in white matter tract microstructure: a multi-cohort study in older adults." Alzheimer's & Dementia, 22(8), e71698. https://doi.org/10.1002/alz.71698
Introduction
This study compared the independent associations of four vascular risk factors with the microstructure of individual white matter tracts.
Methods
Harmonized diffusion MRI data from 2961 adults across five cohorts were analyzed using free-water correction. Models related hypertension, diabetes, heart disease, and body mass index (BMI) to free water and diffusion measurements in 48 tracts, adjusting for covariates.
Results
Hypertension and heart disease had the most consistent, widespread associations. Diabetes findings weakened in sensitivity analyses, while BMI findings varied across measurements. Heart disease showed counterintuitive diffusion patterns that require further investigation.
Discussion
The findings highlight differing relationships between vascular conditions and white matter structure. Further work is needed to clarify mechanisms and establish whether treating these conditions preserves white matter health.
Highlights
- Five cohorts contributed harmonized imaging data.
- Hypertension associations were prominent in the fornix and pre-supplementary motor area transcallosal tract.
- Heart disease associations were prominent in the cingulum and inferior longitudinal fasciculus.
- Diabetes and BMI findings were less consistent.