LeFevre, James D.; Vyas, Yukti; Sathe, Aditi; Shashikumar, Niranjana; Pechman, Kimberly R.; Yang, Yisu; Durant, Alaina; Kanakaraj, Praitayini; Kim, Michael E.; Gao, Chenyu; Newlin, Nancy R.; Ramadass, Karthik; Khairi, Nazirah Mohd; Li, Zhiyuan; Yao, Tianyuan; Risacher, Shannon L.; Zhang, Panpan; Schilling, Kurt G.; Lee, Annie J.; Brickman, Adam M.; Mayeux, Richard; Mez, Jesse; Kukull, Walter; Biber, Sarah A.; Landman, Bennett A.; Bendlin, Barbara B.; Johnson, Sterling C.; Schneider, Julie; Barnes, Lisa L.; Bennett, David A.; Saykin, Andrew J.; Cuccaro, Michael L.; Hohman, Timothy J.; Jefferson, Angela L.; Archer, Derek B. (2026). . Alzheimer’s & Dementia, 22(8), e71698.
Vascular risk factors can contribute to damage in the brain鈥檚 white matter, which contains nerve fibers that connect different brain regions. However, it is unclear how individual risk factors affect specific white matter pathways. This study examined the independent effects of four major vascular risk factors鈥攈igh blood pressure, heart disease, diabetes, and body mass index (BMI)鈥攗sing diffusion MRI data from 2,961 participants across five research cohorts. Researchers assessed microscopic changes in 48 white matter pathways using several measures of tissue structure and water movement. High blood pressure and heart disease showed the strongest and most widespread associations with poorer white matter health. Associations with diabetes became weaker in additional analyses, while findings for BMI varied depending on the measure examined. These results suggest that high blood pressure and heart disease may have particularly important relationships with white matter health, highlighting the potential value of managing these conditions to help preserve brain structure.
FIGURE 1
White matter tractography templates. Forty-eight white matter tractography templates were used in this study and can be grouped into TC (A), association (B), projection (C), and limbic tracts (D). IFG, inferior frontal gyrus; IFOF, inferior fronto-occipital fasciculus; ILF, inferior longitudinal fasciculus; IPL, inferior parietal lobe; M1, primary motor cortex; PMd, dorsal premotor cortex; PMv, ventral premotor; S1, primary somatosensory cortex; SLF, superior longitudinal fasciculus; SLF-TP, temporoparietal superior longitudinal fasciculus; SMA, supplementary motor area; SPL, superior parietal lobe; TC, transcallosal; UF, uncinate fasciculus.