Association of Blood Pressure With Brain Ages: A Cohort Study of Gray and White Matter Aging Discrepancy in Mid-to-Older Adults From UK Biobank

BACKGROUND: Gray matter (GM) and white matter (WM) impairments are both associated with raised blood pressure (BP), although whether elevated BP is differentially associated with the GM and WM aging process remains inadequately examined. METHODS: We included 37 327 participants with diffusion-weighted imaging (DWI) and 39 630 participants with T1-weighted scans from UK Biobank. BP was classified into 4 categories: normal BP, high-normal BP, grade 1, and grade 2 hypertension. Brain age gaps (BAGs) for GM (BAG GM ) and WM (BAG WM ) were derived from diffusion-weighted imaging and T1 scans separately using 3-dimensional-convolutional neural network deep learning techniques. RESULTS: There was an increase in both BAG GM and BAG WM with raised BP ( P <0.05). BAG WM was significantly larger than BAG GM at high-normal BP (0.195 years older; P =0.006), grade 1 hypertension (0.174 years older; P =0.004), and grade 2 hypertension (0.510 years older; P <0.001), but not for normal BP. Mediation analysis revealed that the association between hypertension and cognitive decline was primarily mediated by WM impairment. Mendelian randomization analysis suggested a causal relationship between hypertension and WM aging acceleration (unstandardized B, 1.780; P =0.016) but not for GM ( P >0.05). Sliding-window analysis indicated the association between hypertension and brain aging acceleration was moderated by chronological age, showing stronger correlations in midlife but weaker associations in the older age. CONCLUSIONS: Compared with GM, WM was more vulnerable to raised BP. Our study provided compelling evidence that concerted efforts should be directed towards WM damage in individuals with hypertension in clinical practice.