Hypertension and heart disease are linked to widespread damage in the brain's white matter, according to a new study of older adults, which found altered microstructure across 48 distinct brain tracts. The findings point to tighter management of both conditions as a way to help protect brain health.
METHODOLOGY
- Researchers conducted a cross-sectional analysis of diffusion MRI data from five harmonized cohorts in the Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium, which included measures of cognition, neuroimaging, vascular risk factors (VRFs), fluid biomarkers, and neuropathology.
- A total of 2964 participants (mean age, 75.99 years; 59.35% female) were included, with VRF assessments matched to diffusion tensor imaging scans within a 5-year window.
- Analysis examined associations between four VRFs (hypertension, diabetes, heart disease, and BMI) and white matter microstructure using free water (FW) and FW-corrected (FWcorr) diffusion metrics — fractional anisotropy (FAFWcorr), mean diffusivity, axial diffusivity, and radial diffusivity across 48 white matter tracts.
- Multiple linear regression models controlled for age, sex, education, race/ethnicity, and cognitive status assessed the relative associations of VRFs with white matter microstructure.
TAKEAWAY
- Hypertension was associated with higher FW across 47 of 48 white matter tracts; the strongest association was observed for the transcallosal inferior parietal lobe tract (partial R2, 2.5%; PFDR < .001), suggesting increased extracellular fluid. Higher BMI showed association with higher FW across 17 tracts, while diabetes and heart disease were not associated with FW in any tract.
- Hypertension demonstrated associations with lower FAFWcorr across all 48 tracts, with the strongest effects in the fornix, pre-supplementary motor area transcallosal tract, and inferior temporal gyrus transcallosal tract (PFDR < .001 for all).
- Heart disease showed widespread associations with higher FAFWcorr across all 48 tracts, with the strongest effects in the cingulum, inferior longitudinal fasciculus, and inferior temporal gyrus transcallosal tract (PFDR < .001 for all).
- Diabetes was associated with 32 tracts for higher FAFWcorr, with the strongest effects in the inferior longitudinal fasciculus, temporoparietal superior longitudinal fasciculus, and primary somatosensory cortex projection (PFDR < .001 for all), but these associations were attenuated in sensitivity analyses restricted to 1-year temporal windows.
IN PRACTICE
"Among VRFs, hypertension and heart disease explain the greatest unique variance in white matter microstructure,” the authors of the study wrote. “This study indicates that prioritizing interventions for hypertension and heart disease may more reliably yield greater benefits in preserving white matter integrity compared to BMI and diabetes," they added.
SOURCE
The study was led by James D. LeFevre, Vanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville. It was published online on July 31 in Alzheimer's & Dementia.
LIMITATIONS
VRF variables represented lifetime history or current diagnosis rather than severity, duration, or management status, introducing unmeasured variance. The temporal interval between VRF assessments and diffusion tensor imaging scans (up to 5 years in primary analysis) could introduce exposure misclassification. Some cohorts relied on self-reported VRF data while others used laboratory verification, potentially introducing misclassification bias.
DISCLOSURES
The study was supported by grants from the National Institute on Aging and other sources. Several authors reported receiving consulting fees, serving on advisory boards, or holding editorial positions with various pharmaceutical companies and medical journals. Additional author disclosures are reported in the original article.
https://www.medscape.com/viewarticle/hypertension-and-heart-disease-linked-white-matter-2026a1000qpg
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