Duration-related regional patterns of gray matter alterations in hypertension and their cognitive implications

Hypertension is a major modifiable vascular risk factor for cognitive decline. However, how regional gray matter (GM) alterations differ according to hypertension duration remains incompletely understood. We hypothesized that different brain regions would exhibit heterogeneous GMV profiles across hypertension-duration groups and that regional GMV alterations would be associated with cognitive performance. Structural MRI and cognitive data were obtained from 487 participants with hypertension and 165 normotensive controls. Participants with hypertension were stratified by disease duration (≤ 4, 5-11, and ≥ 12 years). Voxel-based morphometric analysis was used to identify whole-brain GMV alterations across groups. Regional associations with hypertension duration and cognitive performance were subsequently examined, adjusting for age, sex, total intracranial volume, and, where appropriate, education. Regression models further assessed whether GMV-cognition associations differed across hypertension-duration groups. Three cross-sectional duration-related GMV patterns were identified: early and relatively stable alterations, duration-sensitive alterations, and intermediate-to-long-duration alterations. Longer hypertension duration was associated with lower GMV in the right rectus, left middle temporal, and left angular gyri, and higher GMV in the bilateral putamen and right insula after FDR correction. Only greater left thalamic GMV remained associated with higher MoCA scores after correction. Interaction analyses suggested duration-group differences in GMV-cognition associations in the right insula and right precuneus. Hypertension was associated with heterogeneous, region-specific GMV alteration across duration groups rather than a uniform cumulative atrophy pattern. The direction and cognitive relevance of these alterations varied across regions, highlighting the importance of considering hypertension duration when evaluating brain structural alterations. Longitudinal studies are needed to clarify their temporal evolution.